AUTOIMMUNE THROMBOCYTOPENIA

Opportunities of Chronic Myeloid Leukemia Treatment with Reduced Doses of Tyrosine Kinase Inhibitors

AUTOIMMUNE THROMBOCYTOPENIA , ,

MA Guryanova, EYu Chelysheva, AG Turkina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Margarita Anatolevna Guryanova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(985)201-70-40; e-mail: margarita.samtcova@yandex.ru

For citation: Guryanova MA, Chelysheva EYu, Turkina AG. Opportunities of Chronic Myeloid Leukemia Treatment with Reduced Doses of Tyrosine Kinase Inhibitors. Clinical oncohematology. 2021;14(1):118–28. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-118-128

ABSTRACT

Tyrosine kinase inhibitor (TKI) therapy results in deep molecular response (MR) in 60–70 % of chronic myeloid leukemia (CML) patients. However, despite high efficacy of TKIs, many patients experience drug toxicity during the treatment. According to clinical studies, the probability of sustaining off-treatment remission in CML patients with deep MR is about 40–60 %. Great attention has recently been paid to personalized therapy of chronic phase CML. It consists in TKI dose modification to reduce or prevent adverse events. Major retrospective studies proved that in patients with optimal response TKI reduced doses can be considered safe from the point of view of sustaining major and deep MRs achieved with standard TKI doses. Also, prospective clinical trials deal with the follow-up using TKI reduced doses as pre-withdrawal period. But up to now, the results of only 4 of such studies have been available. To take a closer look at long-term follow-up of CML patients receiving reduced doses of TKIs, prospective clinical trials need to be carried out. The present article reviews the results of main studies dealing with management of CML patients treated with TKI reduced doses.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, major molecular response, deep molecular response, adverse events, pharmacokinetics of tyrosine kinase inhibitors.

Received: August 3, 2020

Accepted: November 20, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Туркина А.Г., Новицкая Н.В., Голенков А.К. идр. Регистр больных хроническим миелолейкозом в Российской Федерации: от наблюдательного исследования к оценке эффективности терапии в клинической практике. Клиническая онкогематология. 2017;10(3):390–401. doi: 10.21320/2500-2139-2017-10-3-390-401.
    [Turkina AG, Novitskaya NV, Golenkov AK, et al. Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice. Clinical oncohematology. 2017;10(3):390–401. doi: 10.21320/2500-2139-2017-10-3-390-401. (In Russ)]
  2. Sasaki K, Strom SS, O’Brien S, et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol. 2015;2(5):e186–е193. doi: 10.1016/S2352-3026(15)00048-4.
  3. Hehlmann R, Lauseker M, Saussele S, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31(11):2398–406. doi: 10.1038/leu.2017.253.
  4. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747–57. doi: 10.1016/S1470-2045(18)30192-X.
  5. Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French Stop Imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2017;35(3):298–305. doi: 10.1200/jco.2016.68.2914.
  6. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846–54. doi: 10.1182/blood-2016-09-742205.
  7. Chelysheva EYu, Petrova AN, Shukhov OA, et al. First interim analysis of the Russian multicenter prospective study RU-SKI: discontinuation of tyrosine kinase inhibitors in patients with chronic myeloid leukemia and deep molecular response. Hemasphere. 2018;2(S1):141.
  8. Туркина А.Г., Челышева Е.Ю., Шуваев В.А. и др. Результаты наблюдения больных хроническим миелолейкозом с глубоким молекулярным ответом без терапии ингибиторами тирозинкиназ. Терапевтический архив. 2017;89(12):86–96. doi: 10.17116/terarkh2017891286-96.
    [Turkina AG, Chelysheva EYu, Shuvaev VA, et al. Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy. Terapevticheskii arkhiv. 2017;89(12):86–96. doi: 10.17116/terarkh2017891286-96. (In Russ)]
  9. Зейфман А.А., Челышева Е.Ю., Туркина А.Г. и др. Роль селективности ингибиторов тирозинкиназ в развитии побочных эффектов при терапии хронического миелолейкоза. Клиническая онкогематология. 2014;7(1):16–27.
    [Zeifman AA, Chelysheva EYu, Turkina AG, et al. Role of tyrosine­kinase inhibitor selectivity in development of adverse effects during treatment of chronic myeloid leukemia. Klinicheskaya onkogematologiya. 2014;7(1):16–27. (In Russ)]
  10. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044–54. doi: 10.1038/leu.2016.5.
  11. Cortes JE, Saglio G, Kantarjian H, et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naive Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34(20):2333–40. doi: 10.1200/jco.2015.64.8899.
  12. Ломаиа Е.Г., Романова Е.Г., Сбитякова Е.И. и др. Эффективность и безопасность ингибиторов тирозинкиназ 2-го поколения (дазатиниб, нилотиниб) в терапии хронической фазы хронического миелолейкоза. Онкогематология. 2013;2:22–33.
    [Lomaia EG, Romanova EG, Sbityakova EI, et al. Efficacy and safety of 2nd generation tyrosine kinase inhibitors (dasatinib, nilotinib) in the treatment of chronic phase of chronic myeloid leukemia. Onkogematologiya. 2013;2:22–33. (In Russ)]
  13. Лазорко Н.С., Ломаиа Е.Г., Романова Е.Г. и др. Ингибиторы тирозинкиназ второго поколения и их токсичность у больных в хронической фазе хронического миелолейкоза. Клиническая онкогематология. 2015;8(3):302–8. doi: 10.21320/2500-2139-2015-8-3-302-308.
    [Lazorko NS, Lomaia EG, Romanova EG, et al. Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia. Clinical oncohematology. 2015;8(3):302–8. doi: 10.21320/2500-2139-2015-8-3-302-308. (In Russ)]
  14. Kantarjian H, Pasquini R, Levy V, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R). Cancer. 2009;115(18):4136–47. doi: 10.1002/cncr.24504.
  15. Quintas-Cardama A, Kantarjian H, O’Brien S, et al. Pleural Effusion in Patients With Chronic Myelogenous Leukemia Treated With Dasatinib After Imatinib Failure. J Clin Oncol. 2007;25(25):3908–14. doi: 10.1200/JCO.2007.12.0329.
  16. de Lavallade H, Punnialingam S, Milojkovic D, et al. Pleural effusions in patients with chronic myeloid leukaemia treated with dasatinib may have an immune-mediated pathogenesis. Br J Haematol. 2008;141(5):745–7. doi: 10.1111/j.1365-2141.2008.07108.
  17. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2017;36(3):231–7. doi: 10.1200/jco.2017.74.7162.
  18. Brummendorf HT, Cortes JE, de Souza CA, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol. 2015;168(1):69–81. doi: 10.1111/bjh.13108.
  19. Kerkela R, Grazette I, Yacolti R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12(8):908–16. doi: 10.1038/nm1446.
  20. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–27. doi: 10.1056/nejmoa1609324.
  21. Hadzijusufovic E, Albrecht-Schgoer K, Huber K, et al. Nilotinib-induced vasculopathy: identifi cation of vascular endothelial cells as a primary target site. Leukemia. 2017;31(11):2388–97. doi: 10.1038/leu.2017.245.
  22. Троицкая Е.А., Вельмакин С.В., Кобалава Ж.Д. Концепция сосудистого возраста: новый инструмент оценки сердечно-сосудистого риска. Артериальная гипертензия. 2017;23(2):160–71. doi: 10.18705/1607-419X-2017-23-2-160-171.
    [Troitskaya EA, Velmakin SV, Kobalava ZD. Concept of vascular age: new tool in cardiovascular risk assessment. Arterial’naya gipertenziya. 2017;23(2):160–71. doi: 10.18705/1607-419X-2017-23-2-160-171. (In Russ)]
  23. Туркина А.Г., Лазарева О.В., Челышева Е.Ю. и др. Результаты терапии больных хроническим миелолейкозом по данным российской части международного многоцентрового популяционного исследования Eutos Population-Based Study (EUTOS-PBS). Гематология и трансфузиология. 2019;64(2):106–21. doi: 10.35754/0234-5730-2019-64-2-106-121.
    [Turkina AG, Lazareva OV, Chelysheva EYu, et al. Treatment outcomes in patients with chronic myeloid leukemia according to the Russian part of the EUTOS Population-Based Study. Russian journal of hematology and transfusiology. 2019;64(2):106–21. doi: 10.35754/0234-5730-2019-64-2-106-121. (In Russ)]
  24. Hehlmann R, Lauseker M, Saussele S, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31(11):2398–406. doi: 10.1038/leu.2017.253.
  25. Rousselot P, Johnson-Ansah H, Huguet F, et al. Personalized daily doses of imatinib by therapeutic drug monitoring increase the rates of molecular responses in patients with chronic myeloid leukemia. Final results of the randomized OPTIM imatinib study. Blood. 2015;126(23):133. doi: 10.1182/blood.v126.23.133.133.
  26. Shah NP, Rousselot P, Schiffer C, et al. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016;91(9):869–74. doi: 10.1002/ajh.24423.
  27. Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–8. doi: 10.1200/JCO.2009.26.3087.
  28. Ibrahim AR, Milojkovic D, Bua M, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for CML patients on long term imatinib therapy. Blood. 2010;116(21):3414. doi: 10.1182/blood.v116.21.3414.3414.
  29. Куцев С.И., Шатохин Ю.В. Влияние перерывов терапии иматинибом на достижение цитогенетического и молекулярного ответов у больных хроническим миелолейкозом. Казанский медицинский журнал. 2009;90(6):827–31.
    [Kutsev SI, Shatokhin YuV. Effect of interruptions in imatinib therapy on achievement of cytogenetic and molecular responses in patients with chronic myeloid leukemia. Kazanskii meditsinskii zhurnal. 2009;90(6):827–31. (In Russ)]
  30. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531–41. doi: 10.1056/NEJMoa055229.
  31. Santana-Hernandez P, Pedraza RCP, Duque SG, et al. Low-Dose Dasatinib as First-Line Treatment for Chronic Myeloid Leukemia: Preliminary Report. Blood. 2017;130(Suppl 1):5254.
  32. Naqvi K, Jabbour E, Skinner J, et al. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2020;126(1):67–75. doi: 10.1002/cncr.32504.
  33. Carella AM, Lerma E. Durable responses in chronic myeloid leukemia patients maintained with lower doses of imatinib mesylate after achieving molecular remission. Ann Hematol. 2007;86(10):749–52. doi: 10.1007/s00277-007-0326-2.
  34. Cervantes F, Correa JG, Perez I, et al. Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response. Ann Hematol. 2017;96(1):81–5. doi: 10.1007/s00277-016-2839-z.
  35. Iriyama N, Ohashi K, Hashino S, et al. The efficacy of reduced-dose dasatinib as a subsequent therapy in patients with chronic myeloid leukemia in the chronic phase: the LD-CML study of the Kanto CML Study Group. Intern Med. 2018;57(1):17–23. doi: 10.2169/internalmedicine.9035-17.
  36. Hjorth-Hansen H, Stenke L, Soderlund S, et al. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). Eur J Haematol. 2015;94(3):243–50. doi: 10.1111/ejh.12423.
  37. Santos FP, Kantarjian H, Fava C, et al. Clinical impact of dose reductions and interruptions of second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia. Br J Haematol. 2010;150(3):303–12. doi: 10.1111/j.1365-2141.2010.08245.x
  38. Russo D, Martinelli G, Malagola M, et al. Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia. Blood. 2013;121(26):5138–44. doi: 10.1182/blood-2013-01-480194.
  39. La Rosee P, Martiat P, Leitner A, et al. Improved tolerability by a modified intermittent treatment schedule of dasatinib for patients with chronic myeloid leukemia resistant or intolerant to imatinib. Ann Hematol. 2013;92(10):1345–50. doi: 10.1007/s00277-013-1769-2.
  40. Faber E, Divoka M, Skoumalova I, et al. A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment. Leuk Lymphoma. 2016;57(2):370–5. doi: 10.3109/10428194.2015.1056184.
  41. Шухов О.А., Гурьянова М.А., Челышева Е.Ю. и др. Оценка стабильности молекулярного ответа у больных хроническим миелоидным лейкозом на сниженных дозах ингибиторов тирозинкиназ второго поколения. Гематология и трансфузиология. 2020;65(1, приложение 1):111–2.
    [Shukhov OA, Gur’yanova MA, Chelysheva EYu, et al. Assessment of molecular response stability in chronic myeloid leukemia patients treated with second generation tyrosine kinase inhibitors. Gematologiya i transfuziologiya. 2020;65(1, Suppl 1):111–2. (In Russ)]
  42. Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 2017;4(7):e310–е316. doi: 10.1016/s2352-3026(17)30066-2.
  43. Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019;6(7):e375–е383. doi: 10.1016/S2352-3026(19)30094-8.
  44. Rea D, Cayuela J, Dulucq S, et al. Molecular responses after switching from a standard-dose twice-daily nilotinib regimen to a reduced-dose once-daily schedule in patients with chronic myeloid leukemia: a real life observational study (NILO-RED). Blood 2017;130(1): Abstract 590.
  45. Claudiani S, Apperley J, Khan A, et al. Dose reduction of first and second generation TKI is effective in the maintenance of major molecular response and may predict successful TFR in CML patients. Blood. 2018;132(1): Abstract 3007.
  46. Cayssials E, Torregrosa-Diaz J, Gallego-Hernanz P, et al. Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: results of a retrospective study. Cancer. 2020;126(15):3438–47. doi: 10.1002/cncr.32940.
  47. Singh N, Kumar L, Meena R, et al. Drug monitoring of imatinib levels in patients undergoing therapy for chronic myeloid leukaemia: comparing plasma levels of responders and non-responders. Eur J Clin Pharmacol. 2009;65(6):545–9. doi: 10.1007/s00228-009-0621-z.
  48. Larson RA, Druker BJ, Guilhot F, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111(8):4022–8. doi: 10.1182/blood-2007-10-116475.
  49. Picard S, Titier K, Etienne G, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard dose imatinib in chronic myeloid leukemia. Blood. 2007;109(8):3496–9. doi: 10.1182/blood-2006-07-036012.
  50. Takahashi N, Wakita H, Miura M, et al. Correlation between imatinib pharmacokinetics and clinical response in Japanese patients with chronic-phase chronic myeloid leukemia. Clin Pharmacol Ther. 2010;88(6):809–13. doi: 10.1038/clpt.2010.186.
  51. Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–8. doi: 10.1200/JCO.2009.26.3087.
  52. Куцев С.И., Оксенюк О.С. Мониторинг в терапии хронического миелолейкоза иматинибом. Клиническая онкогематология. 2009;2(3):225–31.
    [Kutsev SI, Oksenyuk OS. Monitoring in imatinib treatment of chronic myeloid leukemia. Klinicheskaya onkogematologiya. 2009;2(3):225–31. (In Russ)]
  53. Larson RA, Yin OQ, Hochhaus A, et al. Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012;68(5):723–33. doi: 10.1007/s00228-011-1200-7.
  54. Takahashi N, Miura M, Kuroki J, et al. Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and he efficacy and safety of nilotinib. Biomark Res. 2014;2(1):6. doi: 10.1186/2050-7771-2-6.
  55. Tanaka C, Yin OQP, Sethuraman V, et al. Clinical pharmacokinetics of the BCR–ABL tyrosine kinase inhibitor nilotinib. Clin Pharmacol Ther. 2010;87(2):197–203. doi: 10.1038/clpt.2009.208.
  56. Miura M. Therapeutic drug monitoring of imatinib, nilotinib, and dasatinib for patients with chronic myeloid leukemia. Biol Pharm Bull. 2015;38(5):645–54. doi: 10.1248/bpb.b15-00103.
  57. Wang X, Roy A, Hochhaus A, et al. Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure–response analysis of a phase III study. Clin Pharmacol. 2013;10(5):85–97. doi: 10.2147/CPAA.S42796.
  58. Mita A, Abumiya M, Miura M, et al. Correlation of plasma concentration and adverse effects of bosutinib: standard dose or dose-escalation regimens of bosutinib treatment for patients with chronic myeloid leukemia. Exp Hematol Oncol. 2018;7(1):9. doi: 10.1186/s40164-018-0101-1.

EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review)

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

NN Mamaev, AI Shakirova, EV Morozova, TL Gindina

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Shakirova AI, Morozova EV, Gindina TL. EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2021;14(1):103–17. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-103-117

ABSTRACT

The present review provides the analysis of theoretical background and therapy of prognostically poorest EVI1-positive myeloid leukemias and myelodysplastic syndromes which is performed at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. The focus is on the evidence of the dominating role of EVI1 gene in impaired epigenetic regulation of hematopoiesis and, thus, on the feasibility of allogeneic hematopoietic stem cell transplantation with hypomethylating agents and/or trans-retinoic acid used for these diseases treatment.

Keywords: EVI1, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, allo-HSCT, hypomethylating agents, trans-retinoic acid.

Received: September 12, 2020

Accepted: December 6, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Barjesteh van Waalwijk van Doorn-Khosrovani S. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood. 2002;101(3):837–45. doi: 10.1182/blood-2002-05-1459.
  2. Lugthart S, van Drunen E, van Norden Y, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood. 2008;111(8):4329–37. doi: 10.1182/blood-2007-10-119230.
  3. Groschel S, Lugthart S, Schlenk RF, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28(12):2101–7. doi: 10.1200/JCO.2009.26.0646.
  4. Paquette RL, Nicoll J, Chalukya M, et al. Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors. Cancer Genet. 2011;204(7):392–7. doi: 10.1016/j.cancergen.2011.06.002.
  5. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миелодиспластические синдромы с высокой экспрессией гена EVI1: теоретические и клинические аспекты. Клиническая онкогематология. 2012;5(4):361–4.
    [Mamaev NN, Gorbunova AV, Gindina TL, et al. Leukemias and myelodysplastic syndromes with high expression of EVI1 gene: theoretical and clinical aspects. Klinicheskaya onkogematologiya. 2012;5(4):361–4. (In Russ)]
  6. Rogers HJ, Vardiman JW, Anastasi J, et al. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99(5):821–9. doi: 10.3324/haematol.2013.096420.
  7. Reiter E, Greinix H, Rabitsch W, et al. Low curative potential of bone marrow transplantation for highly aggressive acute myelogenous leukemia with inversion inv(3)(q21q26) or homologous translocation t(3;3)(q21;q26). Ann Hematol. 2000;79(7):374–7. doi: 10.1007/s002770000158.
  8. He X, Wang Q, Cen J, et al. Predictive value of high EVI1 expression in AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation in first CR. Bone Marrow Transplant. 2016;51(7):921–7. doi: 10.1038/bmt.2016.71.
  9. Gindina TL, Mamaev NN, Afanasyev BV. Chromosome abnormalities and hematopoietic stem cell transplantation in acute leukemias. In: ML Larramendy, S Soloneski (eds). Chromosomal abnormalities – A hallmark manifestation of genomic instability. IntechOpen; 2017. рр. 71– doi: 10.5772/67802.
  10. Halaburda K, Labopin M, Houhou M, et al. AlloHSCT for inv(3)(q21;q26)/t(3;3)(q21;q26) AML: a report from the acute leukemia working party of the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018;53(6):683–91. doi: 10.1038/s41409-018-0165-x.
  11. Martinelli G, Ottaviani E, Buonamici S, et al. Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica. 2003;88(11):1221–8.
  12. Poppe B, Dastugue N, Vandesompele J, et al. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements. Genes Chromos Cancer. 2006;45(4):349–56. doi: 10.1002/gcc.20295.
  13. De Braekeleer M, Le Bris MJ, De Braekeleer E, et al. 3q26/EVI1 rearrangements in myeloid hemopathies: a cytogenetic review. Fut Oncol. 2015;11(11):1675–86. doi: 10.2217/fon.15.64.
  14. Mamaev NN, Gindina TL, Morozova EV, et al. Primary myelodysplastic syndrome with two rare recurrent chromosome abnormalities [t(3q26/2;q22 and trisomy 13] associated with resistance to chemotherapy and hematopoietic stem cell transplantation. Cell Ther Transplant. 2018;7(2):64–9. doi: 10/18620/ctt-1866-8836-2018-7-2-64-69.
  15. Hodge JC, Bosler D, Rubinstein L, et al. Molecular and pathologic characterization of AML with double inv(3)(q21q26.2). Cancer Genet. 2019;230:28–36. doi: 10.1016/j.cancergen.2018.08.007.
  16. Testoni N, Borsaru G, Martinelli G, et al. 3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features. Haematologica. 1999;84(8):690–4.
  17. Russell M, List A, Greenberg P, et al. Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. Blood. 1994;84(4):1243–8. doi: 10.1182/blood.V84.4.1243.1243.
  18. Groschel S, Schlenk RF, Engelmann J, et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol. 2013;31(1):95–103. doi: 10.1200/JCO.2011.41.5505.
  19. Ho PA, Alonzo TA, Gerbing RB, et al. High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children’s oncology group. Br J Haematol. 2013;162(5):670–7. doi: 10.1111/bjh.12444.
  20. Zhang Y, Owens K, Hatem L, et al. Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia. Blood. 2013;122(16):2888–92. doi: 10.1182/blood-2012-08-453662.
  21. Mucenski ML, Taylor BA, Ihle JN, et al. Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors. Mol Cell Biol. 1988;8(1):301–8. doi: 10.1128/mcb.8.1.301.
  22. Goyama S, Kurokawa M. Pathogenetic significance of ecotropic viral integration site-1 in hematological malignancies. Cancer Sci. 2009;100(6):990–5. doi: 10.1111/j.1349-7006.2009.01152.x.
  23. Hinai AA, Valk PJ. Review: Aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2016;172(6):870–8. doi: 10.1111/bjh.13898.
  24. Yuan X, Wang X, Bi K, Jiang G. The role of EVI-1 in normal hematopoiesis and myeloid malignancies (Review). Int J Oncol. 2015;47(6):2028–36. doi: 10.3892/ijo.2015.3207.
  25. Delwel R, Funabiki T, Kreider BL, et al. Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. Mol Cell Biol. 1993;13(7):4291–300. doi: 10.1128/mcb.13.7.4291.
  26. Funabiki T, Kreider BL, Ihle JN. The carboxyl domain of zinc fingers of the Evi-1 myeloid transforming gene binds a consensus sequence of GAAGATGAG. Oncogene. 1994;9(6):1575–81.
  27. Morishita K, Suzukawa K, Taki T, et al. EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC. Oncogene. 1995;10(10):1961–7.
  28. Perkins AS, Kim JH. Zinc fingers 1–7 of EVI1 fail to bind to the GATA motif by itself but require the core site GACAAGATA for binding. J Biol Chem. 1996;271(2):1104–10. doi: 10.1074/jbc.271.2.1104.
  29. Bartholomew C, Kilbey A, Clark AM, Walker M. The Evi-1 proto-oncogene encodes a transcriptional repressor activity associated with transformation. Oncogene. 1997;14(5):569–77. doi: 10.1038/sj.onc.1200864.
  30. Kilbey A, Bartholomew C. Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor region are both required for optimal transformation of Rat1 fibroblasts. Oncogene. 1998;16(17):2287–91. doi: 10.1038/sj.onc.1201732.
  31. Bordereaux D, Fichelson S, Tambourin P, Gisselbrecht S. Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs. Oncogene. 1990;5(6):925–7.
  32. Alzuherri H, McGilvray R, Kilbey A, Bartholomew C. Conservation and expression of a novel alternatively spliced Evi1 exon. Gene. 2006;384:154–62. doi: 10.1016/j.gene.2006.07.027.
  33. Fears S, Mathieu C, Zeleznik-Le N, et al. Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family. Proc Natl Acad Sci USA. 1996;93(4):1642–7. doi: 10.1073/pnas.93.4.1642.
  34. Huang S, Shao G, Liu L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem. 1998;273(26):15933–9. doi: 10.1074/jbc.273.26.15933.
  35. Goyama S, Yamamoto G, Shimabe M, et al. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell. 2008;3(2):207–20. doi: 10.1016/j.stem.2008.06.002.
  36. Laricchia-Robbio L, Nucifora G. Significant increase of self-renewal in hematopoietic cells after forced expression of EVI1. Blood Cells Mol Dis. 2008;40(2):141–7. doi: 10.1016/j.bcmd.2007.07.012.
  37. Yoshimi A, Kurokawa M. Evi1 forms a bridge between the epigenetic machinery and signaling pathways. Oncotarget. 2011;2(7):575–86. doi: 10.18632/oncotarget.304.
  38. Buonamici S, Li D, Chi Y, et al. EVI1 induces myelodysplastic syndrome in mice. J Clin Invest. 2005;115(8):2296. doi: 1172/jci21716c1.
  39. Cuenco GM, Ren R. Both AML1 and EVI1 oncogenic components are required for the cooperation of AML1/MDS1/EVI1 with BCR/ABL in the induction of acute myelogenous leukemia in mice. Oncogene. 2004;23(2):569–79. doi: 10.1038/sj.onc.1207143.
  40. Glass C, Wilson M, Gonzalez R, et al. The role of EVI1 in myeloid malignancies. Blood Cells Mol Dis. 2014;53(1–2):67–76. doi: 10.1016/j.bcmd.2014.01.002.
  41. Jin G, Yamazaki Y, Takuwa M, et al. Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis. Blood. 2007;109(9):3998–4005. doi: 10.1182/blood-2006-08-041202.
  42. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818–22. doi: 10.1038/nature04980.
  43. Bindels EM, Havermans M, Lugthart S, et al. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs. Blood. 2012;119(24):5838–49. doi: 10.1182/blood-2011-11-393827.
  44. Glass C, Wuertzer C, Cui X, et al. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia. PLoS One. 2013;8(6):e67134. doi: 10.1371/journal.pone.0067134.
  45. Hoyt PR, Bartholomew C, Davis AJ, et al. The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development. Mech Dev. 1997;65(1–2):55–70. doi: 10.1016/s0925-4773(97)00057-9.
  46. Nucifora G. The EVI1 gene in myeloid leukemia. Leukemia. 1997;11(12):2022–31. doi: 10.1038/sj.leu.2400880.
  47. Kataoka K, Sato T, Yoshimi A, et al. Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med. 2011;208(12):2403–16. doi: 10.1084/jem.20110447.
  48. Zhang Y, Stehling-Sun S, Lezon-Geyda K, et al. PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function. Blood. 2011;118(14):3853–61. doi: 10.1182/blood-2011-02-334680.
  49. Steinleitner K, Rampetsreiter P, Koffel R, et al. EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages. Anticancer Res. 2012;32(11):4883–9.
  50. Wieser R. The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions. Gene. 2007;396(2):346–57. doi: 10.1016/j.gene.2007.04.012.
  51. Xi ZF, Russell M, Woodward S, et al. Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia. Leukemia. 1997;11(2):212–20. doi: 10.1038/sj.leu.2400547.
  52. Aytekin M, Vinatzer U, Musteanu M, et al. Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 5’-ends. Gene. 2005;356:160–8. doi: 10.1016/j.gene.2005.04.032.
  53. Niederreither K, Subbarayan Y, Dolle P, et al. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet. 1999;21(4):444–8. doi: 1038/7788.
  54. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350(16):1617–28. doi: 10.1056/NEJMoa040465.
  55. Morishita K, Parganas E, William CL, et al. Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300–400 kilobases on chromosome band 3q26. Proc Natl Acad Sci USA. 1992;89(9):3937–41. doi: 10.1073/pnas.89.9.3937.
  56. Ogawa S, Mitani K, Kurokawa M, et al. Abnormal expression of Evi-1 gene in human leukemias. Hum Cell. 1996;9(4):323–32.
  57. Lugthart S, Groschel S, Beverloo HB, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol. 2010;28(24):3890–8. doi: 10.1200/JCO.2010.29.2771.
  58. Groschel S, Sanders MA, Hoogenboezem R, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125(1):133–9. doi: 10.1182/blood-2014-07-591461.
  59. Langabeer SE, Rogers JR, Harrison G, et al. EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2001;112(1):208–11. doi: 10.1046/j.1365-2141.2001.02569.x.
  60. Balgobind BV, Lugthart S, Hollink IH, et al. EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia. Leukemia. 2010;24(5):942–9. doi: 10.1038/leu.2010.47.
  61. Matsuo H, Kajihara M, Tomizawa D, et al. EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia. Haematologica. 2014;99(11):e225–е227. doi: 10.3324/haematol.2014.107128.
  62. Testa U, Lo-Coco F. Targeting of leukemia-initiating cells in acute promyelocytic leukemia. Stem Cell Invest. 2015;2:8. doi: 10.3978/j.issn.2306-9759.2015.04.03.
  63. Jo A, Mitani S, Shiba N, et al. High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML. Leukemia. 2015;29(5):1076–83. doi: 10.1038/leu.2015.5.
  64. Sadeghian MH, Rezaei Dezaki Z. Prognostic Value of EVI1 Expression in Pediatric Acute Myeloid Leukemia: A Systematic Review. Iran J Pathol. 2018;13(3):294–300.
  65. Arai S, Yoshimi A, Shimabe M, et al. Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells. Blood. 2011;117(23):6304–14. doi: 10.1182/blood-2009-07-234310.
  66. De Weer A, Van der Meulen J, Rondou P, et al. EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells. Br J Haematol. 2011;154(3):337–48. doi: 10.1111/j.1365-2141.2011.08737.x.
  67. Yamazaki H, Suzuki M, Otsuki A, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25(4):415–27. doi: 10.1016/j.ccr.2014.02.008.
  68. Groschel S, Sanders MA, Hoogenboezem R, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157(2):369–81. doi: 10.1016/j.cell.2014.02.019.
  69. Lugthart S, Figueroa ME, Bindels E, et al. Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1. Blood. 2011;117(1):234–41. doi: 10.1182/blood-2010-04-281337.
  70. Bartholomew C, Morishita K, Askew D, et al. Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene. Oncogene. 1989;4(5):529–34.
  71. Kreider BL, Orkin SH, Ihle JN. Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. Proc Natl Acad Sci USA. 1993;90(14):6454–8. doi: 10.1073/pnas.90.14.6454.
  72. Kataoka K, Kurokawa M. Ecotropic viral integration site 1, stem cell self-renewal and leukemogenesis. Cancer Sci. 2012;103(8):1371–7. doi: 10.1111/j.1349-7006.2012.02303.x.
  73. Soderholm J, Kobayashi H, Mathieu C, et al. The leukemia-associated gene MDS1/EVI1 is a new type of GATA-binding transactivator. Leukemia. 1997;11(3):352–8. doi: 10.1038/sj.leu.2400584.
  74. Laricchia-Robbio L, Fazzina R, Li D, et al. Point mutations in two EVI1 Zn fingers abolish EVI1-GATA1 interaction and allow erythroid differentiation of murine bone marrow cells. Mol Cell Biol. 2006;26(20):7658–66. doi: 10.1128/MCB.00363-06.
  75. Senyuk V, Sinha KK, Li D, et al. Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis. Cancer Res. 2007;67(12):5658–66. doi: 10.1158/0008-5472.CAN-06-3962.
  76. Laricchia-Robbio L, Premanand K, Rinaldi CR, Nucifora G. EVI1 Impairs myelopoiesis by deregulation of PU.1 function. Cancer Res. 2009;69(4):1633–42. doi: 10.1158/0008-5472.CAN-08-2562.
  77. Steinmetz B, Hackl H, Slabakova E, et al. The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid. Cell Cycle. 2014;13(18):2931–43. doi: 10.4161/15384101.2014.946869.
  78. Yuasa H, Oike Y, Iwama A, et al. Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO J. 2005;24(11):1976–87. doi: 10.1038/sj.emboj.7600679.
  79. Shimabe M, Goyama S, Watanabe-Okochi N, et al. Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene. 2009;28(49):4364–74. doi: 10.1038/onc.2009.288.
  80. Kurokawa M, Mitani K, Irie K, et al. The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3. Nature. 1998;394(6688):92–6. doi: 10.1038/27945.
  81. Izutsu K, Kurokawa M, Imai Y, et al. The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood. 2001;97(9):2815–22. doi: 10.1182/blood.v97.9.2815.
  82. Kurokawa M, Mitani K, Yamagata T, et al. The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J. 2000;19(12):2958–68. doi: 10.1093/emboj/19.12.2958.
  83. Buonamici S, Li D, Mikhail FM, et al. EVI1 abrogates interferon-alpha response by selectively blocking PML induction. J Biol Chem. 2004;280(1):428–36. doi: 10.1074/jbc.M410836200.
  84. Pradhan AK, Mohapatra AD, Nayak KB, Chakraborty S. Acetylation of the proto-oncogene EVI1 abrogates Bcl-xL promoter binding and induces apoptosis. PLoS One. 2011;6(9):e25370. doi: 10.1371/journal.pone.0025370.
  85. Yatsula B, Lin S, Read AJ, et al. Identification of binding sites of EVI1 in mammalian cells. J Biol Chem. 2005;280(35):30712–22. doi: 10.1074/jbc.M504293200.
  86. Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42(8):722–6. doi: 10.1038/ng.621.
  87. Figueroa ME, Lugthart S, Li Y, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 2010;17(1):13–27. doi: 10.1016/j.ccr.2009.11.020.
  88. Wagner JM, Hackanson B, Lubbert M, Jung M. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin Epigenet. 2010;1(3–4):117–36. doi: 10.1007/s13148-010-0012-4.
  89. Senyuk V, Zhang Y, Liu Y, et al. Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis. Proc Natl Acad Sci USA. 2013;110(14):5594–9. doi: 10.1073/pnas.1302645110.
  90. Nikoloski G, Langemeijer SM, Kuiper RP, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 2010;42(8):665–7. doi: 10.1038/ng.620.
  91. Makishima H, Jankowska AM, Tiu RV, et al. Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies. Leukemia. 2010;24(10):1799–804. doi: 10.1038/leu.2010.167.
  92. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33. doi: 10.1056/NEJMoa1005143.
  93. Walter MJ, Ding L, Shen D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia. 2011;25(7):1153–8. doi: 10.1038/leu.2011.44.
  94. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301. doi: 10.1056/NEJMoa0810069.
  95. Langemeijer SM, Kuiper RP, Berends M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41(7):838–42. doi: 10.1038/ng.391.
  96. Gelsi-Boyer V, Trouplin V, Adelaide J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145(6):788–800. doi: 10.1111/j.1365-2141.2009.07697.x.
  97. van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41(5):521–3. doi: 10.1038/ng.349.
  98. Liu Y, Chen L, Ko TC, et al. Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT. Oncogene. 2006;25(25):3565–75. doi: 10.1038/sj.onc.1209403.
  99. Yoshimi A, Goyama S, Watanabe-Okochi N, et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood. 2011;117(13):3617–28. doi: 10.1182/blood-2009-12-261602.
  100. Bingemann SC, Konrad TA, Wieser R. Zinc finger transcription factor ecotropic viral integration site 1 is induced by all-trans retinoic acid (ATRA) and acts as a dual modulator of the ATRA response. FEBS J. 2009;276(22):6810–22. doi: 10.1111/j.1742-4658.2009.07398.x.
  101. Pauebelle E, Plesa A, Hayette S, et al. Efficacy of All-Trans-Retinoic Acid in high-risk acute myeloid leukemia with overexpression of EVI1. Oncol Ther. 2019;7(2):121–30. doi: 10.1007/s40487-019-0095-9.
  102. Vazquez I, Maicas M, Cervera J, et al. Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia. Haematologica. 2011;96(10):1448–56. doi: 10.3324/haematol.2011. 040535.
  103. Daghistani M, Marin D, Khorashad JS, et al. EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors. Blood. 2010;116(26):6014–7. doi: 10.1182/blood-2010-01-264234.
  104. Мамаев Н.Н., Шакирова А.И., Бархатов И.М. идр. Ведущая роль BAALC-экспрессирующих клеток-предшественниц в возникновении и развитии посттрансплантационных рецидивов у больных острыми миелоидными лейкозами. Клиническая онкогематология. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88.
    [Mamaev NN, Shakirova AI, Barkhatov IM, et al. Crucial Role of BAALC–Expressing Progenitor Cells in Emergence and Development of Post-Transplantation Relapses in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88. (In Russ)]
  105. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8. doi: 10.1038/367645a0.
  106. Matsushita H, Yahata T, Sheng Y, et al. Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice. PLoS One. 2014;9(11):e111082. doi: 10.1371/journal.pone.0111082.
  107. Cole CB, Verdoni AM, Ketkar S, et al. PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia. J Clin Invest. 2016;126(1):85–98. doi: 10.1172/JCI82897.
  108. Гудожникова Я.В., Мамаев Н.Н., Бархатов И.М. и др. Результаты молекулярного мониторинга в посттрансплантационный период с помощью серийного исследования уровня экспрессии гена WT1 у больных острыми миелоидными лейкозами. Клиническая онкогематология. 2018;11(3):241–51. doi: 10.21320/2500-2139-2018-11-3-241-251.
    [Gudozhnikova YaV, Mamaev NN, Barkhatov IM, et al. Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2018;11(3):241–51. doi: 10.21320/2500-2139-2018-11-3-241-251. (In Russ)]
  109. Dreyfus F, Bouscary D, Melle J, et al. Expression of the Evi-1 gene in myelodysplastic syndromes. Leukemia. 1995;9(1):203–5. doi: 10.1016/0145-2126(94)90237-2.
  110. Thol F, Yun H, Sonntag AK, et al. Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes. Ann Hematol. 2012;91(8):1221–33. doi: 10.1007/s00277-012-1457-7.
  111. Russell M, Thompson F, Spier C, Taetle R. Expression of the EVI1 gene in chronic myelogenous leukemia in blast crisis. Leukemia. 1993;7(10):1654–7.
  112. Ogawa S, Kurokawa M, Tanaka T, et al. Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia. Leukemia. 1996;10(5):788–94.
  113. Kuila N, Sahoo DP, Kumari M, et al. EVI1, BAALC and AME: prevalence of the secondary mutations in chronic and accelerated phases of chronic myeloid leukemia patients from eastern India. Leuk Res. 2009;33(4):594–6. doi: 10.1016/j.leukres.2008.07.018.
  114. Горбунова А.В., Гиндина Т.Л., Морозова Е.В. и др. Влияние молекулярно-генетических и цитогенетических факторов на эффективность аллогенной трансплантации костного мозга у больных хроническим миелолейкозом. Клиническая онкогематология. 2013;6(4):445–50.
    [Gorbunova AV, Gindina TL, Morozova EV, et al. Impact of molecular genetic and cytogenetic characteristics on outcomes of allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia. Klinicheskaya oncogematologiya. 2013;6(4):445–50. (In Russ)]
  115. Sato T, Goyama S, Kataoka K, et al. Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Oncogene. 2014;33(42):5028–38. doi: 10.1038/onc.2014.108.
  116. Konantz M, Andre MC, Ebinger M, et al. EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia. Leukemia. 2013;27(1):56–65. doi: 10.1038/leu.2012.211.
  117. Mittal N, Li L, Sheng Y, et al. A critical role of epigenetic inactivation of miR-9 in EVI1high pediatric AML. Mol Cancer. 2019;18(1):30. doi: 10.1186/s12943-019-0952-z.
  118. Verhagen HJ, Smit MA, Rutten A, et al. Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid. Blood. 2016;127(4):458–63. doi: 10.1182/blood-2015-07-653840.
  119. Мамаев Н.Н, Горбунова А.В, Гиндина Т.Л. и др. Стойкое восстановление донорского гемопоэза у больной с посттрансплантационным рецидивом острого миеломонобластного лейкоза с inv(3)(q21q26), моносомией 7 и экспрессией онкогена EVI1 после трансфузий донорских лимфоцитов и использования гипометилирующих агентов. Клиническая онкогематология. 2014;7(1):71–5.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Stable donor hematopoiesis reconstitution after post­transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), –7 and EVI1 oncogene overexpression treated by donor lymphocyte infusions and hypomethylating agents. Klinicheskaya oncogematologiya. 2014;7(1):71–5. (In Russ)]
  120. He X, Wang Q, Cen J, et al. Predictive value of high EVI1 expression in AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation in first CR. Bone Marrow Transplant. 2016;51(7):921–7. doi: 10.1038/bmt.2016.71.
  121. Мамаев Н.Н., Морозова Е.В., Горбунова А.В. Теоретические и клинические аспекты эпигенетических изменений при миелодиспластических синдромах и острых нелимфобластных лейкозах (обзор литературы). Вестник гематологии. 2011;7(3):12–21.
    [Mamaev NN, Morozova EV, Gorbunova AV. Theoretical and practical aspects of epigenetic changes in myelodysplastic syndromes and acute non-lymphoblastic leukemias (literature review). Vestnik gematologii. 2011;7(3):12–21. (In Russ)]
  122. Mamaev N, Morozova E, Gindina T, et al. Dacogen and allogeneic bone marrow transplantation in the treatment of high-risk myelodysplastic syndromes with non-random chromosome abnormalities. Leuk Res. 2011;35(Suppl 1):72–3. doi: 10.1016/S0145-2126(11)70186-2.
  123. Mamaev N, Gorbunova A, Barkhatov I, et al. Biology and treatment of leukemia and myelodysplastic syndromes with high EVI-1 gene expression. ELN Frontiers Meeting 2012 “Myeloid neoplasms: approaching cure”. Istanbul, Turkey. Abstract No. 37.
  124. Yang X, Wong MPM, Ng RK. Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications. Int J Mol Sci. 2019;20(18):4576. doi: 10.3390/ijms20184576.
  125. Nowek K, Sun SM, Dijkstra MK, et al. Expression of a passenger miR-9* predicts favorable outcome in adults with acute myeloid leukemia less than 60 years of age. Leukemia. 2016;30(2):303–9. doi: 10.1038/leu.2015.282.
  126. Li F, He W, Geng R, Xie X. Myeloid leukemia with high EVI1 expression is sensitive to 5-aza-2’-deoxycytidine by targeting miR-9. Clin Transl Oncol. 2020;22(1):137–43. doi: 10.1007/s12094-019-02121-y.
  127. Cattaneo F, Nucifora G. EVI1 recruits the histone methyltransferase SUV39H1 for transcription repression. J Cell Biochem. 2008;105(2):344–52. doi: 10.1002/jcb.21869.
  128. Craddock C, Quek L, Goardon N, et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia. 2013;27(5):1028–36. doi: 10.1038/leu.2012.312.
  129. Trino S, Zoppoli P, Carella AM, et al. DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation. Stem Cell Res Ther. 2019;10(1):138. doi: 10.1186/s13287-019-1245-6.
  130. Ahn JS, Kim YK, Min YH, et al. Azacitidine Pre-Treatment Followed by Reduced-Intensity Stem Cell Transplantation in Patients with Higher-Risk Myelodysplastic Syndrome. Acta Haematol. 2015;134(1):40–8. doi: 10.1159/000368711.
  131. Voso MT, Leone G, Piciocchi A, et al. Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study. Ann Oncol. 2017;28(7):1547–53. doi: 10.1093/annonc/mdx154.
  132. Овечкина В.Н., Бондаренко С.Н., Морозова Е.В. и др. Роль терапии гипометилирующими препаратами перед аллогенной трансплантацией гемопоэтических стволовых клеток при острых миелоидных лейкозах и миелодиспластическом синдроме. Клиническая онкогематология. 2017;10(3):351–7. doi: 10.21320/2500-2139-2017-10-3-351-357.
    [Ovechkina VN, Bondarenko SN, Morozova EV, et al. The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2017;10(3):351–7. doi: 10.21320/2500-2139-2017-10-3-351-357. (In Russ)]
  133. Nishihori T, Perkins J, Mishra A, et al. Pretransplantation 5-azacitidine in high-risk myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014;20(6):776–80. doi: 10.1016/j.bbmt.2014.02.008.
  134. de Lima M, Giralt S, Thall PF, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010;116(23):5420–31. doi: 10.1002/cncr.25500.
  135. Craddock C, Jilani N, Siddique S, et al. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial. Biol Blood Marrow Transplant. 2016;22(2):385–90. doi: 10.1016/j.bbmt.2015.09.004.
  136. Marini C, Brissot E, Bazarbachi A, et al. Tolerability and Efficacy of Treatment With Azacytidine as Prophylactic or Preemptive Therapy for Myeloid Neoplasms After Allogeneic Stem Cell Transplantation. Clin Lymphoma Myel Leuk. 2020;20(6):377–82. doi: 10.1016/j.clml.2019.10.011.
  137. Бадаев Р.Ш., Заммоева Д.Б., Гиршова Л.Л. и др. Профилактическое применение азацитидина у пациентов с острыми миелоидными лейкозами после гаплоидентичной аллоТКМ. Клиническая онкогематология. 2019;12(1):37–42. doi: 10.21320/2500-2139-2019-12-1-37-42.
    [Badaev RSh, Zammoeva DB, Girshova LL, et al. Preventive Use of Azacitidine in Patients with Acute Myeloid Leukemia after Haploidentical Allo-BMT. Clinical oncohematology. 2019;12(1):37–42. doi: 10.21320/2500-2139-2019-12-1-37-42. (In Russ)]
  138. Cattaneo F, Nucifora G. EVI1 recruits the histone methyltransferase SUV39H1 for transcription repression. J Cell Biochem. 2008;105(2):344–52. doi: 10.1002/jcb.21869.
  139. Estey EH, Thall PF, Pierce S, et al. Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin ± all-trans retinoic acid ± granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Blood. 1999;93(8):2478–84. doi: 10.1182/blood.v93.8.2478.
  140. Schlenk RF, Frohling S, Hartmann F, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004;18(11):1798–803. doi: 10.1038/sj.leu.2403528.
  141. Raza A, Buonamici S, Lisak L, et al. Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression. Leuk Res. 2004;28(8):791–803. doi: 10.1016/j.leukres.2003.11.018.
  142. Burnett AK, Hills RK, Green C, et al. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood. 2010;115(5):948–56. doi: 10.1182/blood-2009-08-236588.
  143. van Gils N, Verhagen HJMP, Smit L. Reprogramming acute myeloid leukemia into sensitivity for retinoic-acid-driven differentiation. Exp Hematol. 2017;52:12–23. doi: 10.1016/j.exphem.2017.04.007.
  144. Plesa A, Dumontet C, Mattei E, et al. High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia. World J Stem Cells. 2017;9(12):227–34. doi: 10.4252/wjsc.v9.i12.227.
  145. Nguyen CH, Bauer K, Hackl H, et al. All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia. Cell Death Dis. 2019;10(12):944. doi: 10.1038/s41419-019-2172-2.
  146. Field T, Perkins J, Huang Y, et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010;45(2):255–60. doi: 10.1038/bmt.2009.134.
  147. Kim DY, Lee JH, Park YH, et al. Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant. 2012;47(3):374–9. doi: 10.1038/bmt.2011.86.
  148. Jiang YZ, Su GP, Dai Y, et al. Effect of Decitabine Combined with Unrelated Cord Blood Transplantation in an Adult Patient with -7/EVI1+ Acute Myeloid Leukemia: a Case Report and Literature Review. Ann Clin Lab Sci. 2015;45(5):598–601.
  149. Schlenk RF, Lubbert M, Benner A, et al. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 2016;95(12):1931–42. doi: 10.1007/s00277-016-2810-z.
  150. Taussig DC, Vargaftig J, Miraki-Moud F, et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction. Blood. 2010;115(10):1976–84. doi: 10.1182/blood-2009-02-206565.
  151. Patel S, Zhang Y, Cassinat B, et al. Successful xenografts of AML3 samples in immunodeficient NOD/shi-SCID IL2Rγ–/– Leukemia. 2012;26(11):2432–5. doi: 10.1038/leu.2012.154.

Organ Lesions in Adults with Secondary Hemophagocytic Syndrome

AUTOIMMUNE THROMBOCYTOPENIA

VG Potapenko1,2, AV Klimovich1, DD Avdoshina3, VV Baikov2, NV Vinogradova3, OV Goloshchapov2, EV Doguzhieva3, EE Zinina4, GV Kachenya3, YuA Krivolapov5, EV Karyagina6, TG Kulibaba7, SV Lapin2, EE Leenman5, ES Pavlyuchenko5, NA Potikhonova8, MYu Pervakova2, NB Popova4, AV Rysev9, VV Ryabchikova1, EA Surkova2, IP Fedunyak3, NV Medvedeva1

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

3 SP Botkin Clinical Hospital for Infectious Diseases, 3 Mirgorodskaya str., Saint Petersburg, Russian Federation, 191167

4 Surgut District Clinical Hospital, 24 bld. 2 Energetikov str., Surgut, Russian Federation, 628408

5 II Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 191015

6 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

7 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

8 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

9 II Dzhanelidze Saint Petersburg Research Institute of Emergency Medicine, 3 Budapeshtskaya str., Saint Petersburg, Russian Federation, 192242

For correspondence: Vsevolod Gennadevich Potapenko, MD, PhD, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Klimovich AV, Avdoshina DD, et al. Organ Lesions in Adults with Secondary Hemophagocytic Syndrome. Clinical oncohematology. 2021;14(1):91–102. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-91-102

ABSTRACT

Background. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure.

Aim. To describe organ lesions characteristic of SHPS patients.

Materials & Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively.

Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2–90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions.

Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.

Keywords: hemophagocytic syndrome, ferritin, inflammation, cytokine storm, etoposide, Epstein-Barr virus infection.

Received: August 2, 2020

Accepted: November 29, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Janka GE, Lehmberg K. Hemophagocytic syndromes – an update. Blood Rev. 2014;28(4):135–42. doi: 10.1016/j. blre.2014.03.002.
  2. Farquhar JW, Claireaux AE. Familial haemophagocytic reticulosis. Arch Dis Childhood. 1952;27(136):519–25. doi: 10.1136/adc.27.136.519.
  3. Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127(22):2672–81. doi: 10.1182/blood-2016-01-690636.
  4. Birndt S, Schenk T, Heinevetter B, et al. Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry. J Cancer Res Clin Oncol. 2020;146(4):1065–77. doi: 10.1007/s00432-020-03139-4.
  5. Arca M, Fardet L, Galicier L. Prognostic factors of early death in a cohort of 162 adult haemophagocytic syndrome: impact of triggering disease and early treatment with etoposide. Br J Haematol. 2015;168(1):63–8. doi: 10.1111/bjh.13102.
  6. Zhang Q, Li L, Zhu L, et al. Adult onset haemophagocytic lymphohistiocytosis prognosis is affected by underlying disease: analysis of a single-institution series of 174 patients. Swiss Med Wkly. 2018;148:w doi: 10.4414/smw.2018.14641.
  7. Масчан М.А. Молекулярно-генетическая диагностика и дифференцированная терапия гистиоцитарных пролиферативных заболеваний у детей: Автореф. дис.… д-ра мед. наук. М., 2011. 62 с.
    [Maschan MA. Molekulyarno-geneticheskaya diagnostika i differentsirovannaya terapiya gistiotsitarnykh proliferativnykh zabolevanii u detei. (Molecular genetic diagnosis and differential therapy of histiocytic proliferative diseases in children.) [dissertation] Moscow; 2011. 62 p. (In Russ)]
  8. Trottestam H, Horne A, Arico M, et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. 2011;118(17):4577–84. doi: 10.1182/blood-2011-06-356261.
  9. Harris P, Dixit R, Norton R. Coxiella burnetii causing haemophagocytic syndrome: a rare complication of an unusual pathogen. Infection. 2011;39(6):579–82. doi: 10.1007/s15010-011-0142-4.
  10. Lambotte O, Fihman V, Poyart C, et al. Listeria monocytogenes skin infection with cerebritis and haemophagocytosis syndrome in a bone marrow transplant recipient. J Inf Secur. 2005;50(4):356–8. doi: 10.1016/j.jinf.2004.03.016.
  11. La Rosee P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465–77. doi: 10.1182/blood.2018894618.
  12. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31. doi: 10.1002/pbc.21039.
  13. Rhoades CJ, Williams MA, Kelsey SM, et al. Monocyte-macrophage system as targets for immunomodulation by intravenousimmunoglobulin. Blood Rev. 2000;14(1):14–30. doi: 10.1054/blre.1999.0121.
  14. Li J, Wang Q, Zheng W, et al. Hemophagocytic Lymphohistiocytosis: Clinical Analysis of 103 Adult Patients. Medicine (Baltimore). 2014;93(2):100–5. doi: 10.1097/md.0000000000000022.
  15. Костик М.М., Дубко М.Ф., Масалова В.В. и др. Современные подходы к диагностике и лечению синдрома активации макрофагов у детей с ревматическими заболеваниями. Современная ревматология. 2015;9(1):55–9. doi: 10.14412/1996-7012-2015-1-55-59.
    [Kostik MM, Dubko MF, Masalova VV, et al. Current approaches to diagnosing and treating macrophage activation syndrome in children with rheumatic diseases. Modern rheumatology. 2015;9(1):55–9. doi: 10.14412/1996-7012-2015-1-55-59. (In Russ)]
  16. Machaczka M, Vaktna SJ, Klimkowska M, Hagglund H. Malignancy-associated hemophagocytic lymphohistiocytosis in adults: a retrospective population-based analysis from a single center. Leuk Lymphoma. 2011;52(4):613–9. doi: 10.3109/10428194.2010.551153.
  17. Sano H, Kobayashi R, Tanaka J, et al. Risk factor analysis of non-Hodgkin lymphoma associated haemophagocytic syndromes: a multicentre study. Br J Haematol. 2014;165(6):786–92. doi: 10.1111/bjh.12823.
  18. Delavigne K, Berard E, Bertoli S, et al. Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy. Haematologica. 2014;99(3):474–80. doi: 10.3324/haematol.2013.097394.
  19. Seguin A, Galicier L, Boutboul D, et al. Pulmonary Involvement in Patients With Hemophagocytic Lymphohistiocytosis. Chest. 2016;149(5):1294–301. doi: 10.1016/j.chest.2015.11.004.
  20. Reginato AJ, Schumacher HR Jr, Baker DG, et al. Adult onset Still’s disease: experience in 23 patients and literature review with emphasis on organ failure. Semin Arthrit Rheumatol. 1987;17(1):39–57. doi: 10.1016/0049-0172(87)90015-1.
  21. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a Score for the diagnosis of reactive hemophagocytic syndrome. Arthrit Rheumatol. 2014;66(9):2613–20. doi: 10.1002/art.38690.
  22. Практическое руководство по ультразвуковой диагностике. Общая ультразвуковая диагностика. Под ред. В.В. Митькова. М.: Издательский дом Видар, 2005. 720 с.
    [Mitkov VV, ed. Prakticheskoe rukovodstvo po ul’trazvukovoi diagnostike. Obshchaya ul’trazvukovaya diagnostika. (Practice guidelines for sonography. General sonography.) Moscow: Vidar Publ.; 2005. 720 p. (In Russ)]
  23. Клиническая оценка лабораторных тестов: Пер. с англ. Под ред. Н.У. Тица. М.: Медицина, 1986. 480 с.
    [Tietz NW, ed. Clinical guide to laboratory tests. (Russ. ed.: Tits NU. Klinicheskaya otsenka laboratornykh testov. Moscow: Meditsina; 1986. 480 p.)]
  24. Worwood M, Cragg SJ, Williams AM, et al. The clearance of 131I-human plasma ferritin in man. Blood. 1982;60(4):827–33. doi: 10.1182/blood.v4.827.827.
  25. Потапенко В.Г., Первакова М.Ю., Титов А.В. и др. Клинико-лабораторная характеристика и дифференциальная диагностика вторичного гемофагоцитарного синдрома и сепсиса. Клиническая онкогематология. 2019;12(3):329–37. doi: 10.21320/2500-2139-2019-12-3-329-337.
    [Potapenko VG, Pervakova MYu, Titov AV, et al. Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis. Clinical oncohematology. 2019;12(3):329–37. doi: 10.21320/2500-2139-2019-12-3-329-337. (In Russ)]
  26. Сборник протоколов и алгоритмов химиотерапии и сопроводительного лечения лейкозов, миелодисплазий и аплазий кроветворения. Под ред. В.Г. Савченко. М., 2008. Том I.
    [Savchenko VG, ed. Sbornik protokolov i algoritmov khimioterapii i soprovoditel’nogo lecheniya leikozov, mielodisplazii i aplazii krovetvoreniya. (Collection of protocols and algorithms for chemotherapy and accompanying treatment of leukemias, myelodysplasias and aplasias.) Moscow; 2008. Vol. I. (In Russ)]
  27. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых [электронный документ]. Доступно по: https://www.blood.ru/documents/clinical%20guidelines/21.%20klinicheskie-rekomendacii-2014-oml.pdf. Ссылка активна на 29.10.2020.
    [Savchenko VG, Parovichnikova ЕN, Afanasyev BV, et al. Clinical guidelines for the diagnosis and treatment of acute myeloid leukemias in adults. [Internet] Available from: https://www.blood.ru/documents/clinical%20guidelines/21.%20klinicheskie-rekomendacii-2014-oml.pdf. (accessed 10.2020) (In Russ)]
  28. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Клинические рекомендации по диагностике и лечению острых лимфобластных лейкозов взрослых. (редакция 2018) [электронный документ]. Доступно по: https://npngo.ru/uploads/media_document/293/556718e9-0ff5-46f3-bff8-bd592c83bpdf. Ссылка активна на 29.10.2020.
    [Savchenko VG, Parovichnikova ЕN, Afanasyev BV, et al. Clinical guidelines for the diagnosis and treatment of acute lymphoblastic leukemias in adults. [Internet] Available from: https://npngo.ru/uploads/media_document/293/556718e9-0ff5-46f3-bff8-bd592c83b992.pdf. (accessed 29.10.2020) (In Russ)]
  29. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2018.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines on diagnosis and treatment of lymphoproliferative disorders.) Moscow: Buki Vedi Publ.; 2018. (In Russ)]
  30. Okano M, Kawa K, Kimura H, et al. Proposed Guidelines for Diagnosing Chronic Active Epstein-Barr Virus Infection. Am J Hematol. 2005;80(1):64–9. doi: 10.1002/ajh.20398.
  31. Румянцев А.Г., Масчан А.А. Федеральные клинические рекомендации по диагностике и лечению гемофагоцитарного лимфогистиоцитоза. М., 2014.
    [Rumyantsev AG, Maschan AA. Federalnye klinicheskie rekomendatsii po diagnostike i lecheniyu gemofagotsitarnogo limfogistiotsitoza. (Federal guidelines for the diagnosis and treatment of hemophagocytic lymphohistiocytosis.) Moscow; 2014. (In Russ)]
  32. Руднов В.А. Клинические рекомендации по диагностике и лечению тяжелого сепсиса и септического шока в лечебно-профилактических организациях Санкт-Петербурга. Вестник анестезиологии и реаниматологии. 2016;13(5):88–94.
    [Rudnov VA. Clinical guidelines for the diagnosis and treatment of severe sepsis and septic shock in health and preventive facilities of Saint Petersburg. Vestnik anesteziologii i reanimatologii. 2016;13(5):88–94. (In Russ)]
  33. Xu XJ, Tang YM, Song H, et al. Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children. J Pediatr. 2012;160(6):984–90. doi: 10.1016/j.jpeds.2011.11.046.
  34. Jenkins MR, Rudd-Schmidt JA, Lopez JA, et al. Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time. J Exp Med. 2015;212(3):307–17. doi: 10.1084/jem.20140964.
  35. Put K, Avau A, Brisse E, et al. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-gamma. Rheumatology. 2015;54(8):1507–17. doi: 10.1093/rheumatology/keu524.
  36. Kerguenec C, Hillaire S, Molinie V, et al. Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases. Am J Gastroenterol 2001;96(3):852–7. doi: 10.1111/j.1572-0241.2001.03632.x.
  37. Tsui WM, Wong KF, Tse CC. Liver changes in reactive haemophagocytic syndrome. Liver. 2008;12(6):363–7. doi: 10.1111/j.1600-0676.1992.tb00590.x.
  38. Schmidt MH, Sung L, Shuckett BM. Hemophagocytic lymphohistiocytosis in children: abdominal US findings within 1 week of presentation. Radiology. 2004;230(3):685–9. doi: 10.1148/radiol.2303030223.
  39. Fitzgerald NE, MacClain KL. Imaging characteristics of hemophagocytic lymphohistiocytosis. Pediatr Radiol. 2003;33(6):392–401. doi: 10.1007/s00247-003-0894-9.
  40. Strenger V, Merth G, Lackner H, et al. Malignancy and chemotherapy induced haemophagocytic lymphohistiocytosis in children and adolescents–a single centre experience of 20 years. Ann Hematol. 2018;97(6):989–98. doi: 10.1007/s00277-018-3254-4.
  41. Yoshida N, Ishii E, Oshima K, et al. Engraftment and dissemination of T lymphocytes from primary haemophagocytic lymphohistiocytosis in scid mice. Br J Haematol. 2003;121(2):349–58. doi: 10.1046/j.1365-2141.2003.04273.x.
  42. Gratton SM, Powell TR, Theeler BJ, et al. Neurological involvement and characterization in acquired hemophagocytic lymphohistiocytosisin adulthood. J Neurol Sci. 2015;357(1–2):136–42. doi: 10.1016/j.jns.2015.07.017.
  43. Cai G, Wang Y, Liu X, et al. Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study. Ann Hematol. 2017;96(8):1279–85. doi: 10.1007/s00277-017-3035-5.
  44. Algahtani H, Absi A, Bassuni W, et al. Adult-onset hemophagocytic lymphohistiocytosis type 2 presenting as a demyelinating disease. Mult Scler Relat Disord. 2018;25:77–82. doi: 10.1016/j.msard.2018.07.031.
  45. Fan ZD, Qian XQ, Yu HG. Pancytopenia as an early indicator for Stevens-Johnson syndrome complicated with hemophagocytic lymphohistiocytosis: a case report. BMC Pediatr. 2014;14(1):38. doi: 10.1186/1471-2431-14-38.
  46. Jun HJ, Kim HO, Lee JY, et al. Preceding Annular Skin Lesions in a Patient with Hemophagocytic Lymphohistiocytosis. Ann Dermatol. 2015;27(5):608–11. doi: 10.5021/ad.2015.27.5.608.
  47. Zerah ML, DeWitt CA. Cutaneous findings in hemophagocytic lymphohistiocytosis. Dermatology. 2015;230(3):234–43. doi: 10.1159/000368552.
  48. Thornton CS, Minoo P, Schneider M, et al. Severe skin disease in lupus associated with hemophagocytic lymphohistiocytosis: case reports and review of the literature. BMC Rheumatol. 2019;3(1):7. doi: 10.1186/s41927-019-0055-x.
  49. Dolinay T, Kim YS, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med. 2012;185(11):1225–34. doi: 10.1164/rccm.201201-0003OC.
  50. Потапенко В.Г., Потихонова Н.А., Байков В.В. и др. Вторичный гемофагоцитарный синдром у взрослых в клинической практике гематолога: обзор литературы и собственные данные. Клиническая онкогематология. 2015;8(2):169–84. doi: 10.21320/2500-2139-2015-8-2-169-184.
    [Potapenko VG, Potikhonova NA, Baikov VV, et al. Secondary Hemophagocytic Syndrome in Adult Patients: Literature Review and Authors’ Experience. Clinical oncohematology. 2015;8(2):169–84. doi: 10.21320/2500-2139-2015-8-2-169-184. (In Russ)]
  51. Bal A, Mishra B, Singh N, et al. Fulminant parvovirus B19-associated pancarditis with haemophagocytic lympho-histiocytosis in an immunocompetent adult. APMIS. 2009;117(10):773–7. doi: 10.1111/j.1600-0463.2009.02528.x.
  52. Letsas KP, Filippatos GS, Delimpasi S, et al. Enterovirus-induced fulminant myocarditis and hemophagocytic syndrome. J Infect. 2007;54(2):e75–е77. doi: 10.1016/j.jinf.2006.04.006.
  53. Kwon CM, Jung YW, Yun DY, et al. A case of acute pericarditis with hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus. Rheumatol Int. 2008;28(3):271–3. doi: 10.1007/s00296-007-0401-y.
  54. Kawamura Y, Miura H, Matsumoto Y, et al. A case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with severe cardiac complications. BMC Pediatr. 2016;16(1):172. doi: 10.1186/s12887-016-0718-3.
  55. Altook R, Ruzieh M, Singh A, et al. Hemophagocytic Lymphohistiocytosis in the Elderly. Am J Med Sci. 2019;357(1):67–74. doi: 10.1016/j.amjms.2018.07.004.
  56. Vandergheynst F, Gosset J, van de Borne P, et al. Myopericarditis revealing adult-onset Still’s disease. Acta Clin Belg. 2005;60(4):205–8. doi: 10.1179/acb.2005.037.
  57. Brito-Zeron P, Kostov B, Moral-Moral P, et al. Prognostic factors of death in 151 adults with hemophagocytic syndrome: etiopathogenically driven analysis. Mayo Clin Proceed Innov Qual Outcome. 2018;2(3):267–76. doi: 10.1016/j.mayocpiqo.2018.06.006.
  58. Schaer DJ, Schaer CA, Schoedon G, et al. Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis. Eur J Haematol. 2006;77(5):432–6. doi: 10.1111/j.1600-0609.2006.00730.x.
  59. Listinsky CM. Common reactive erythrophagocytosis in axillary lymph nodes. Am J Clin Pathol. 1988;90(2):189–92. doi: 10.1093/ajcp/90.2.189.
  60. Потапенко В.Г., Карпушин А.А., Леенман Е.Е. и др. Лихорадка, ассоциированная с металлоконструкцией. Клиническое наблюдение. Журнал инфектологии. 2019;11(3):126–9.
    [Potapenko VG, Karpushin AA, Leenman EE, et al. Fever associated with metalwork. Case report. Zhurnal infektologii. 2019;11(3):126–9. (In Russ)]
  61. Ost A, Nilsson-Ardnor S, Henter JI. Autopsy findings in 27 children with haemophagocytic lymphohistiocytosis. Histopathology. 1998;32(4):310–6. doi: 10.1046/j.1365-2559.1998.00377.x.
  62. Gupta A, Weitzman S, Abdelhaleem M. The role of hemophagocytosis in bone marrow aspirates in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(2):192–4. doi: 10.1002/pbc.21441.
  63. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr. 2007;166(2):95–109. doi: 10.1007/s00431-006-0258-1.
  64. Jordan MB, Hildeman D, Kappler J, et al. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood. 2004;104(3):735– doi: 10.1182/blood-2003-10-3413.
  65. Takada H, Nomura A, Ohga S, Hara T. Interleukin-18 in hemophagocytic lymphohistiocytosis. Leuk Lymphoma. 2001;42(1–2):21– doi: 10.3109/10428190109097673.

Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience

AUTOIMMUNE THROMBOCYTOPENIA ,

AM Kovrigina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Prof. Alla Mikhailovna Kovrigina, PhD in Biology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM. Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience. Clinical oncohematology. 2021;14(1):80–90. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-80-90

ABSTRACT

Background. Pathomorphological analysis of lymph node tissues in immune-mediated lymphadenopathies commonly presupposes differential diagnosis with tumors of lymphoid and myeloid tissues with partial lesions in lymph nodes. Besides, further study is required on pathogenetic relationship between autoimmune diseases with lymphadenopathy and Kikuchi-Fujimoto disease (KFD) with morphological substrate characterized by histiocytic necrotizing lymphadenitis.

Aim. To compare, based on biopsy material, morpho-immunohistochemical characteristics of changes in lymph node tissues in patients with pathomorphological diagnosis of KFD and in patients with autoimmune diseases with lymphadenopathy, i.e. systemic lupus erythematosus (SLE) and adult Still’s disease (ASD).

Materials & Methods. Morphological and immunohistochemical analyses were carried out on lymph node biopsies of 20 patients, 16 out of them with KFD (men/women 15:1, median age 26.5 years, range 18–47 years; in 44 % of cases lesions were only in cervical lymph nodes). In 2 female patients (aged 19 and 33 years) SLE was diagnosed based on clinical and laboratory data, and 2 patients (a woman aged 43 years and a man aged 25 years) were diagnosed with ASD.

Results. Morphological and immunohistochemical analyses detected three major cell populations similar in KFD and SLE and probably reflecting pathogenetic relationship of these diseases: histiocytes expressing myeloperoxidase (MPO+), CD123+ plasmacytoid dendritic cells, cytotoxic CD8+ T-cells, and granzyme B+. In 55 % of KFD cases and 2 SLE cases there were many activated CD30+ lymphoid cells clustered and scattered in the areas of cytotoxic T-cells.

Conclusion. To exclude SLE during subsequent additional examination of patients with morphological substrate characterized by histiocytic necrotizing lymphadenitis it is reasonable to use the term “Kikuchi-like changes” instead of KFD. When the data of immunohistochemical analysis in KFD, SLE, and ASD patients are compared, MPO+ histiocytes in lymph node tissue can serve as diagnostic immunohistochemical marker of immunoinflammatory process. If they are detected, differential diagnosis with myeloid sarcoma is required. CD30 expression by activated cytotoxic lymphoid cells was identified in SLE and in 55 % of KFD cases, which is another important common diagnostic characteristic of the substrate of two diseases (KFD and SLE) and requires differential diagnosis with anaplastic large-cell lymphoma and Hodgkin’s lymphoma. Within the analyzed group of 20 patients morphological substrate of lymph nodes in 2 ASD patients differed in its morphological and immunohistochemical parameters from that in KFD and SLE patients and was characterized by expanded paracortex and morpho-immunohistochemical characteristics of extrafollicular B-cell activation.

Keywords: morphology, immunohistochemistry, Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis, systemic lupus erythematosus, adult Still’s disease, CD30, myeloperoxidase.

Received: July 30, 2020

Accepted: December 2, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Jeon YK, Paik JH, Park SS, et al. Spectrum of lymph node pathology in adult onset Still’s disease; analysis of 12 patients with one follow up biopsy. J Clin Pathol. 2004;57(10):1052–6. doi: 10.1136/jcp.2004.018010.
  2. Cush JJ, Medsger TA, Christy WC, et al. Adult-onset Still’s disease. Arthrit Rheum. 1987;30(2):186–94. doi: 10.1002/art.1780300209.
  3. Kojima M, Nakamura S, Itoh H, et al Systemic Lupus Erythematosus (SLE) Lymphadenopathy Presenting with Histopathologic Features of Castleman’ Disease: A Pathologic Study of Five Cases. Pathol Res Pract. 1997;193(8):565–71 doi: 10.1016/S0344-0338(97)80015-5.
  4. Graef E, Magliulo D, Hollie N, et al. Clinical Characteristics of Lymphadenopathy in Systemic Lupus Erythematous: A Case Control Study from a Tertiary Care Center. Arthrit Rheumatol. 2019;71(Suppl 10): Abstract.
  5. Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis. Nippon Ketsueki Gakkai Zasshi. 1972;35:379–80.
  6. Fujimoto Y, Kozima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. A new clinicopathological entity. Naika. 1972;20:920–7.
  7. Pileri S, Kikuchi M, Helbron D, Lennert K. Histiocytic necrotizing lymphadenitis without granulocytic infiltration. Virch Arch Pathol Anat. 1982;395(3):257–71. doi: 10.1007/bf00429352.
  8. Turner RR, Martin J, Dorfman RF. Necrotizing lymphadenitis. A study of 30 cases. Am J Surg Pathol. 1983;7(2):115–23.
  9. Feller AC, Lennert K, Stein H, et al. Immunohistology and etiology of histiocytic necrotizing lymphadenitis: report of three instructive cases. Histopathology. 1983;7(6):825–39. doi: 1111/j.1365–2559.1983.tb02299.x.
  10. Dorfman RF. Histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto. Arch Pathol Lab Med. 1987;111(11):1026–9.
  11. Sumiyoshi Y, Kikuchi M, Ohshima K, et al Human herpesvirus-6 genomes in histiocytic necrotizing lymphadenitis (Kikuchi’s disease) and other forms of lymphadenitis. Am J Clin Pathol. 1993;99(5):609–14. doi: 10.1093/ajcp/99.5.609.
  12. Huh J, Kang GH, Gong G, et al. Kaposi’s sarcoma associated herpesvirus in Kikuchi’s disease. Hum Pathol. 1998;29(10):1091–6. doi: 10.1016/S0046-8177(98)90419-1.
  13. Chiu CF, Chow KC, Lin TY, et al. Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan. Detection of Epstein-Barr virus, type 1 human T-cell lymphotropic virus, and parvovirus B19. Am J Clin Pathol. 2000;113(6):774–81. doi: 10.1309/1A6Y-YCKP-5AVF-QTYR.
  14. Adoue D, Rauzy O, Rigal-Huguet F. Syndrome de Kikuchi, infection a Cytomegalovirus et maladie lupique. Rev Med Intern. 1997;18(4):338–42. doi: 10.1016/s0248-8663(97)84023-4.
  15. Imamura M, Ueno H, Matsuura A, et al. An ultrastructural study of subacute necrotizing lymphadenitis. Am J Pathol. 1982;107(3):292–9.
  16. Meyer O, Kahn MF, Grossin M, et al. Parvovirus B19 infection can induce histiocytic necrotizing lymphadenitis (Kikuchi’s disease) associated with systemic lupus erythematosus. Lupus. 1991;1(1):37–41. doi: 10.1177/096120339100100107.
  17. Lamzaf L, Harmouche H, Maamar M, et al. Kikuchi-Fujimoto disease: Report of 4 cases and review of the literature. Eur Ann Otorhinolaryngol Head Neck Dis. 2014;131(6):329–32. doi: 10.1016/j.anorl.2013.01.007.
  18. Ferrao E, Grade M, Arez L, et al. Kikuchi-Fujimoto’s disease associated to a systemic erythematosus lupus: a clinical case. Eur J Intern Med. 2003;14:S76. doi: 10.1016/S0953-6205(03)91417-8.
  19. Merwald-Fraenk H, Wiesent F, Dorfler R, et al. Lymphadenitis und systemischer Lupus erythematodes. Z Rheumatol. 2016,75(10):1028–31. doi: 10.1007/s00393-016-0170-7.
  20. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. Medicine (Baltimore). 2014;93(24):372–82. doi: 10.1097/0000000000000220.
  21. Kishimoto K, Tate G, Kitamura T, et al. Cytologic features and frequency of plasmacytoid dendritic cells in the lymph nodes of patients with histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). Diagn Cytopathol. 2010;38(7):521–6. doi: 10.1002/dc.21265.
  22. Lennert K, Remmele W. Karyometric research on lymph node cells in man. I. Germinoblasts, lymphoblasts & lymphocytes. Acta Haematol. 1958;19(2):99–113. doi: 10.1159/000205419.
  23. Ronnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J Exp Med. 2001;194(12):F59–F64. doi: 10.1084/jem.194.12.f59.
  24. Pabon-Porras MA, Molina-Rios S, Florez-Suarez JB. Rheumatoid arthritis and systemic lupus erythematosus: Pathophysiological mechanisms related to innate immune system. SAGE Open Med. 2019;7:1–24. doi: 10.1177/2050312119876146.
  25. Barrat FJ, Su LJ. A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection. Exp Med. 2019;216(9):1974–85. doi: 10.1084/jem.20181359.
  26. Rollins-Raval MA, Marafioti T, Swerdlow SH, Roth CG. The number and growth pattern of plasmacytoid dendritic cells vary in different types of reactive lymph nodes: an immunohistochemical study. Hum Pathol. 2013;44(6):1003–10. doi: 10.1016/j.humpath.2012.08.020.
  27. Katsiari CG, Liossis S-NC, Sfikakis PP. The Pathophysiologic Role of Monocytes and Macrophages in Systemic Lupus Erythematosus: A Reappraisal. Semin Arthrit Rheum. 2010;39(6):491–503. doi: 10.1016/j.semarthrit.2008.11.002.
  28. Ma W-T, Gao F, Gu K, et al. The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review. Front Immunol. 2019;10:1140. doi: 10.3389/fimmu.2019.01140.
  29. Pileri SA, Facchetti F, Ascani S, et al. Myeloperoxidase expression by histiocytes in Kikuchi’s and Kikuchi-like lymphadenopathy. Am J Pathol. 2001;159(3):915–24. doi: 10.1016/S0002-9440(10)61767-1.
  30. Strzepa A, Pritchard KA, Dittel BN. Myeloperoxidase: A new player in autoimmunity. Cell Immunol. 2017;317:1–8. doi: 10.1016/j.cellimm.2017.05.002.
  31. Pilichowska ME, Pinkus JL, Pinkus GS. Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease). Am J Clin Pathol. 2009;131(2):174–82. doi: 10.1309/AJCP7V1QHJLOTKKJ.
  32. Jang SJ, Min JH, Kim D, Yang WI. Myeloperoxidase positive histiocytes in subacute necrotizing lymphadenitis express both CD11c and CD163. Basic Appl Pathol. 2011;4(4):110–5. doi: 10.1111/j.1755-9294.2011.01114.x.
  33. Andersen MH, Schrama D, Straten PT, et al. Cytotoxic T cells. J Invest Dermatol. 2006;126(1):32–41. doi: 10.1038/sj.jid.5700001.
  34. Suarez-Fueyo A, Bradley SJ, Tsokos GC. T cells in Systemic Lupus Erythematosus. Curr Opin Immunol. 2016;43:32–8. doi: 10.1016/j.coi.2016.09.001.
  35. Tabata T, Takata K, Miyata-Takata T, et al. Characteristic Distribution Pattern of CD30-positive Cytotoxic T Cells Aids Diagnosis of Kikuchi-Fujimoto Disease. Appl Immunohistochem Mol Morphol. 2018;26(4):274–82. doi: 10.1097/pai.0000000000000411.
  36. Salman-Monte TC, Ruiz JP, Almirall M, et al. Lymphadenopathy syndrome in systemic lupus erythematosus: Is it Kikuchi-Fujimoto disease? Reumatol Clin. 2017;13(1):55–6. doi: 10.1016/j.reumae.2016.04.004.
  37. Sukswai N, Jung HR, Amr SS. Immunopathology of Kikuchi-Fujimoto Disease: A reappraisal using novel immunohistochemistry markers. Histopathology. 2020;77(2):262–74. doi: 10.1111/his.14050.

Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, AA Zhernyakova1, IM Zapreeva1, ZhYu Sidorova1, NYu Semenova1, EV Karyagina2, EI Stepchenkova3,4, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

3 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

4 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Zapreeva IM, et al. Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(1):73–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-73-79

ABSTRACT

Background. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an indispensable treatment stage in patients with newly diagnosed multiple myeloma (MM) who are, based on age and health status, eligible for high-dose chemotherapy with subsequent auto-HSCT. However, the issue of double (tandem) auto-HSCT feasibility remains unresolved.

Aim. To compare overall survival (OS) and progression-free survival (PFS) in MM patients after single and double (tandem) auto-HSCTs in clinical practice.

Materials & Methods. Retrospective analysis enrolled 83 MM patients divided into two groups: with single (n = 41) and double (n = 42) auto-HSCTs. Median age in groups 1 and 2 was 58 years (range 42–68) and 54 years (range 40–65), respectively. In these groups there were 16 (39 %) and 11 (26.2 %) patients ≥ 60 years old. The reference point of survival curve was the date of first (in group 1) and 2nd (in group 2) auto-HSCTs. In PFS assessment, completed event was the date of disease progression or relapse detection, including the biochemical one in case of specific therapy onset.

Results. Total number of patients with ≥ very good partial response before receiving auto-HSCT in group 1 was 23 (56.1 %), and in group 2 before receiving 2nd auto-HSCT it was 30 (71.4 %). Mel200 conditioning was administered to 53.7 % of patients in group 1. In group 2 this conditioning regimen was a priority in performing first auto-HSCT (83.3 % of patients) and was more rarely used in case of repeated transplantation (40.5 %). With median follow-up of 11 and 40.5 months in groups 1 and 2 no significant differences were identified either in median PFS (21 and 40 months; р = 0.154) or in median OS (not reached in both groups; p = 0.882). No differences between groups with respect to the time before relapse/progression or early relapse rate were observed.

Conclusion. Repeated auto-HSCT showed no additional antitumor effect. It can be accounted for by the lack of data on chromosome aberrations at the disease onset in most patients and by a small number of patients in the groups. Nevertheless, it was decided to limit the number of tandem auto-HSCTs and to perform 2nd transplantation mostly in case of late relapse/progression. New studies were initiated which will focus on the search of predictors associated with survival improvement in MM patients while performing double (tandem) auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, single auto-HSCT, double (tandem) auto-HSCTs, survival.

Received: July 15, 2020

Accepted: November 20, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.
    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]
  2. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24.
    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24. (In Russ)]
  3. Soekojo CY, Kumar S. Stem-cell transplantation in multiple myeloma: how far have we come? Ther Adv Hematol. 2019;10:1–16. doi: 10.1177/2040620719888111.
  4. Moreau P, Attal M. All transplantation-eligible patients with myeloma should receive ASCT in first response. Hematology Am Soc Hematol Educ Program. 2014;2014(1):250–4. doi: 10.1182/asheducation-2014.1.250.
  5. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroup Francais du Myeloma. N Engl J Med. 1996;335(2):91–7. doi: 10.1056/NEJM199607113350204.
  6. Child J, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–83. doi: 1056/NEJMoa022340.
  7. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311–20. doi: 10.1056/NEJMoa1611750.
  8. Suzuki K. Latest treatment strategies aiming for a cure in transplant-eligible multiple myeloma patients: how I cure younger MM patients with lower cost. Int J Hematol. 2020;111(4):512–8. doi: 10.1007/s12185-020-02841-w.
  9. Al Hamed R, Bazarbachi AH, Malard F, et al. Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J. 2019;9(4):44. doi: 10.1038/s41408-019-0205-9.
  10. Gonsalves WI, Buadi FK, Ailawadhi S, et al. Utilization of hematopoietic stem cell transplantation for the multiple myeloma: a Mayo Stratification of Myeloma and risk adapted therapy (mSMART) consensus statement. Bone Marrow Tranplant. 2019;54(3):353–67. doi: 10.1038/s41409-018-0264-8.
  11. Kumar SK, Buadi FK, Rajkumar S. Pros and cons of frontline autologous transplant in multiple myeloma: the debate over timing. Blood. 2019;133(7):652–9. doi: 10.1182/blood-2018-08-825349.
  12. Kunacheewa C, Lee HC, Patel K, et al. Minimal residual disease negativity does not overcome poor prognosis in the high-risk multiple myeloma: a single-center study. Clin Lymphoma Myel Leuk. 2020;20(5):e221–e238. doi: 10.1016/j.clml.2020.01.001.
  13. Chakraborty R, Muchtar E, Kumar SK, et al. Impact of post-transplant response and minimal residual disease on survival in myeloma with high-risk cytogenetics. Biol Blood Marrow Transplant. 2017;23(4):598–605. doi: 10.1016/j.bbmt.2017.01.076.
  14. Cavo M, Petrucci MT, Di Raimondi F, et al. Upfront single versus double autologous stem cell transplantation for newly diagnosed multiple myeloma: an intergroup, multicenter, phase III study of the European Myeloma Network (EMN02/HO95 MM Trial). 2016;128(Suppl 1):991. doi: 10.1182/blood.V128.22.991.991.
  15. Cavo M, Gay FM, Patriarca F, et al. Double autologous stem cell transplantation significantly prolongs progression-free survival and overall survival in comparison with single autotransplantation in newly diagnosed multiple myeloma: an analysis of phase 3 EMN02/HO95 study. Blood. 2017;130(Suppl 1):401. doi: 10.1182/blood.V130.Suppl_1.401.401.
  16. Stadtmauer EA, Pasquini MC, Blackwell B, et al. Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide (Len) and dexamethasone (RVD) consolidation with Len maintenance (ACM), tandem autoHCT with Len maintenance (TAM) and autoHCT with Len maintenance (AM) for up-front treatment of patients with multiple myeloma (MM): primary results from the randomized phase III trial of the blood and marrow transplant clinical trials network (BMT CTN 0702 – StaMINA Trial). 2016;128(22):LBA-1. doi: 10.1182/blood.V128.22.LBA-1.LBA-1.
  17. Stadtmauer EA, Pasquini MC, Blackwell B, et al. Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37(7):589–97. doi: 10.1200/JCO.18.00685.
  18. Cavo M, Goldschmidt H, Rosinol L, et al. Double vs single autologous stem cell transplantation for newly diagnosed multiple myeloma: long-term follow-up (10-years) analysis of randomized phase 3 studies. Blood. 2018;132(Suppl 1):124. doi: 10.1182/blood-2018-99-112899.
  19. Ntanasis-Stathopoulos I, Gavriatopoulou M, Kastritis E, et al. Multiple myeloma: Role of autologous transplantation. Cancer Treat Rev. 2020;82:101929. doi: 10.1016/j.ctrv.2019.101929.
  20. Sonneveld P, Avet-Loiseau H, Lonial S, et al. treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127(24):2955–62. doi: 10.1182/blood-2016-01-631200.
  21. Blocka J, Hielscher T, Goldschmidt H, Hillengass J. Response improvement rather than response status after first autologous stem cell transplantation is a significant prognostic factor for survival benefit from tandem compared with single transplantation in multiple myeloma patients. Biol Blood Marrow Transplant. 2020;26(7):1280–7. doi: 10.1016/j.bbmt.2020.03.006.
  22. Goldschmidt H, Mai EK, Durig J, et al. Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. 2020;34(7):1853–65. doi: 10.1038/s41375-020-0724-1.
  23. Dimopoulos MA, Jakubowiak AJ, McCarthy PL, et al. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma. Blood Cancer J. 2020;10(2):17. doi: 10.1038/s41408-020-0273-x.
  24. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35(29):3279–89. doi: 10.1200/JCO.2017.72.6679.
  25. Gonsalves WI, Kansagra A. Second autologous hematopoietic cell transplant as salvage therapy for relapsed multiple myeloma: a global treatment option for eligible patients. Acta Haematol. 2018;139(1):45–6. doi: 10.1159/000486272.
  26. Muta T, Miyamoto T, Kamimura T, et al. Significance of salvage autologous stem cell transplantation for relapsed multiple myeloma: A nationwide retrospective study in Japan. Acta Haematol. 2018;139(1):35–44. doi: 10.1159/000484652.
  27. Cook G, Ashcroft AJ, Cairns DA, et al. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): A randomised, open-label, phase 3 trial. Lancet Haematol. 2016;3(7):e340–е351. doi: 10.1016/S2352-3026(16)30049-7.

Chronic Lymphocytic Leukemia in Blood Relatives: Two Case Reports of Male Siblings

AUTOIMMUNE THROMBOCYTOPENIA ,

NV Kurkina1,2, EA Repina1

1 NP Ogarev National Research Mordovia State University, 68 Bolshevistskaya str., Saransk, Russian Federation, 430005

2 Republican Clinical Hospital No. 4, 32 Ul’yanova str., Saransk, Russian Federation, 430032

For correspondence: Nadezhda Viktorovna Kurkina, MD, PhD, 32 Ul’yanova str., Saransk, Russian Federation, 430032; e-mail: nadya.kurckina@yandex.ru

For citation: Kurkina NV, Repina EA. Chronic Lymphocytic Leukemia in Blood Relatives: Two Case Reports of Male Siblings. Clinical oncohematology. 2021;14(1):69–72. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-69-72

ABSTRACT

In recent years there are more and more evidences for a hereditary factor in malignant lymphoproliferative disorders. Various lymphoid tumors are diagnosed in blood relatives. This is most frequently observed in chronic lymphocytic leukemia: 13.3 % vs. 8.8 % in non-Hodgkin’s lymphoma and 5.9 % in Hodgkin’s lymphoma. This paper presents two case reports of chronic lymphocytic leukemia in blood relatives (male siblings). Besides, in one of them the efficacy of targeted therapy with ibrutinib is estimated.

Keywords: chronic lymphocytic leukemia, heredity, ibrutinib, refractoriness, relapse.

Received: June 25, 2020

Accepted: November 6, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Zenz T, Gribben JG, Hallek M, et al. Risk categories and refractory CLL in the era of chemoimmunotherapy. Blood. 2012;119(18):4101–7. doi: 10.1182/blood-2011-11-312421.
  2. Никитин Е.А., Судариков А.Б. Хронический лимфолейкоз высокого риска: история, определение, диагностика и лечение. Клиническая онкогематология. 2013;6(1):59–67.
    [Nikitin EA, Sudarikov AB. High­risk chronic lymphocytic leukemia: history, definition, diagnosis, and management. Klinicheskaya onkogematologiya. 2013;6(1):59–67. (In Russ)]
  3. Богданов А.Н., Кулибаба Т.Г. Острые и хронические лейкозы: учебное пособие. СПб.: Изд-во Санкт-Петербургского университета, 2019. 116 с.
    [Bogdanov AN, Kulibaba TG. Ostrye i khronicheskie leikozy: uchebnoe posobie. (Acute and chronic lymphocytic leukemias: Study guide.) Saint Petersburg: Sankt-Peterburgskii universitet Publ.; 2019. 116 p. (In Russ)]
  4. Клиническая гематология. Под ред. Шт. Берчану. М.: Медицинское издательство, 1985. 1224 с.
    [Berchanu Sht, ed. Klinicheskaya gematologiya. (Clinical hematology.) Moscow: Meditsinskoe izdatelstvo Publ.; 1224 p. (In Russ)]
  5. Лейкозы у детей: Клиническое пособие. Под ред. Г.Л. Менткевич, С.А. Маяковой. М.: Практическая медицина, 2009. 384 с.
    [Mentkevich GL, Mayakova SA, eds. Leikozy u detei: Klinicheskoe posobie. (Leukemias in children: Clinical guide.) Moscow: Prakticheskaya meditsina Publ.; 2009. 384 p. (In Russ)]
  6. Клиническая онкогематология: Руководство для врачей. Под ред. М.А. Волковой. М.: Медицина, 2001. 576 с.
    [Volkova MA, ed. Klinicheskaya onkogematologiya: Rukovodstvo dlya vrachei. (Clinical oncohematology: Guidelines for physicians.) Moscow: Meditsina Publ.; 2001. 576 p. (In Russ)]
  7. Медицинская энциклопедия INFO. Хронический миелолейкоз (электронный документ). Доступно по: http://meddaily.info/?cat=article&id=1311. Ссылка активна на 6.11.2020г.
    [MEDDAILY.INFO medical encyclopedia. Chronic myeloid leukemia. [Internet] Available from: http://meddaily.info/?cat=article&id=1311. (accessed 6.11.2020) (In Russ)]
  8. Балакирева Т.В., Андреева Н.Е. Макроглобулинемия Вальденстрема. Клиническая онкогематология. 2009;2(2):121–36.
    [Balakireva TV, Andreeva NE. Waldenstrom’s Klinicheskaya onkogematologiya. 2009;2(2):121–36. (In Russ)]
  9. NCCN Clinical Practice Guidelines in Oncology. Waldenstrom’s Macrogobulinemia/Lymphoplasmacytic Lymphoma. Version 2.2016. Available from: https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf (accessed 6.11.2020).
  10. Brown JR, Neuberg D, Phillips K, et al. Prevalence of familial malignancy in a prospectively screened cohort of patients with lymphoproliferative disorders. Br J Haematology. 2008;143(3):361–8. doi: 10.1111/j.1365-2141.2008.07355.x.
  11. Программное лечение заболеваний системы крови: Сборник алгоритмов диагностики и протоколов лечения заболеваний системы крови. Под ред. В.Г. Савченко. М.: Практика, 2012. 1056 с.
    [Savchenko VG, ed. Programmnoe lechenie zabolevanii sistemy krovi: Sbornik algoritmov diagnostiki i protokolov lecheniya zabolevanii sistemy krovi. (Programmed treatment of hematological diseases: Collection of diagnostic algorithms and treatment protocols of hematological diseases.) Moscow: Praktika Publ.; 1056 p. (In Russ)]

Hodgkin’s Lymphoma in HIV-Infected Patients

AUTOIMMUNE THROMBOCYTOPENIA

AV Pivnik1, AM Vukovich2, NV Kremneva1, MG Dubnitskaya1, AV Tsakhilova1

1 AS Loginov Moscow Clinical Scientific Center, 86 Entuziastov sh., Moscow, Russian Federation, 111123

2 IM Sechenov First Moscow State Medical University, 8 bld. 2 Trubetskaya str., Moscow, Russian Federation, 119991

For correspondence: Prof. Aleksandr Vasilevich Pivnik, MD, PhD, 86 Entuziastov sh., Moscow, Russian Federation, 111123; Tel.: +7(906)065-99-32; e-mail: pivnikav@gmail.com

For citation: Pivnik AV, Vukovich AM, Kremneva NV, et al. Hodgkin’s Lymphoma in HIV-Infected Patients. Clinical oncohematology. 2021;14(1):63–8. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-63-68

ABSTRACT

Aim. To assess clinical and laboratory characteristics of the unique category of HIV-positive patients with hepatitis C or B co-infection combined with Hodgkin’s lymphoma (HL).

Materials & Methods. The paper provides data on 85 HIV-positive patients with HL followed-up at the Department of Hematology and Secondary Immunodeficiencies of the AS Loginov Moscow Clinical Scientific Center from 2002 to 2019 (data on 2008–2010 are not available). The distribution of patients by sex was approximately equal, median age was 35 years (range 20–74 years).

Results. Histological HL variant is predominantly mixed-cell with many positive tests for Epstein-Barr virus. More than 80 % of patients with concomitant HIV infection were admitted to the AS Loginov Center with HL stage III/IV. Most of them received highly active anti-retroviral therapy (HAART) before HL diagnosis. The distinguishing feature of HIV-positive patients with HL appeared to be high (as compared to HIV patients with other lymphoma variants) CD4+ lymphocyte count. This phenomenon is considered within the framework of immune reconstitution inflammatory syndrome (IRIS). A clue to this phenomenon may lay the foundation in addressing the issue of lymphoma genesis and development. Viral load was moderate and undetectable. Hepatitis C and/or B co-infection was identified in 75 % of patients. Antiviral therapy for concomitant hepatitis C was administered concurrent with HAART. All patients received АBVD, BEACOPP-14, BEACOPP-escalated, DHAP, ESHAP antitumor regimens. Radiotherapy was used if necessary. In hepatitis C HAART and direct-acting drugs were administered concurrent with chemotherapy. No severe adverse reactions were observed. Even before starting antitumor treatment of HL patients with concomitant HIV and/or hepatitis viral infections, mortality was 8 %. But in the group of patients with the same co-infections who received HL chemotherapy, mortality was 10 %. The cause of death was HL stage IVB with viral liver cirrhosis, agranulocytosis, and sepsis.

Conclusion. Diseases considered incurable in the past, such as HL and hepatitis C, can be healed today. Compromised immunity of HIV-positive patients can be successfully stabilized with HAART.

Keywords: Hodgkin’s lymphoma, HIV infection, immune reconstitution inflammatory syndrome (IRIS).

Received: April 4, 2020

Accepted: November 9, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Geller SA. Comments on the anniversary of the description of Hodgkin’s disease. J Natl Med Assoc. 1984;76(8):815–817.
  2. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswold’s meeting. J Clin Oncol. 1989;7(11):1630–6. doi: 10.1200/jco.1989.7.11.1630.
  3. Демина Е.А., Тумян Г.С., Чекан А.А. и др. Редкое заболевание — нодулярная лимфома Ходжкина с лимфоидным преобладанием: обзор литературы и собственные наблюдения. Клиническая онкогематология. 2014;7(4):522–32.
    [Demina EA, Tumyan GS, Chekan AA, et al. Rare Disease — Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma: Literature Review and Own Data. Klinicheskaya onkogematologiya. 2014;7(4):522–32. (In Russ)]
  4. Гурцевич В.Э. Вирус Эпштейна—Барр и классическая лимфома Ходжкина. Клиническая онкогематология. 2016;9(2):101–14. doi: 10.21320/2500-2139-2016-9-2-101-114.
    [Gurtsevitch VE. Epstein-Barr Virus and Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(2):101–14. doi: 10.21320/2500-2139-2016-9-2-101-114. (In Russ)]
  5. Демина Е.А. Брентуксимаб ведотин: новые возможности лечения рецидивов и рефрактерных форм лимфомы Ходжкина. Клиническая онкогематология. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405.
    [Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405. (In Russ)]
  6. Демина Е.А. Блокада PD-1-пути ниволумабом — новая возможность иммунотерапии классической лимфомы Ходжкина. Клиническая онкогематология. 2018;11(3):213–9. doi: 10.21320/2500-2139-2018-11-3-213-219.
    [Demina EA. PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(3):213–9. doi: 10.21320/2500-2139-2018-11-3-213-219. (In Russ)]
  7. Насибов О.М. Фиброз легких, кардиопатии и вторичных опухоли у лиц в длительной ремиссии лимфогранулематоза: Дис.… канд. мед. наук. М., 2000. 114 с.
    [Nasibov OM. Fibroz legkikh, kardiopatii i vtorichnykh opukholi u lits v dlitelnoi remissii limfogranulematoza. (Pulmonary fibrosis, cardiopathies and secondary tumors during long lymphogranulomatosis remission.) [dissertation] Moscow; 2000. 114 p. (In Russ)]
  8. Куприна И.В. Состояние щитовидной железы и особенности липидного обмена у больных лимфогранулематозом молодого и среднего возраста после комбинированной химиолучевой терапии: Дис.… канд. мед. наук. М., 2008. 122 с.
    [Kuprina IV. Sostoyanie shchitovidnoi zhelezy i osobennosti lipidnogo obmena u bolnykh limfogranulematozom molodogo i srednego vozrasta posle kombinirovannoi khimioluchevoi terapii. (Thyroid status and lipid metabolism characteristics in young and middle-aged lymphogranulomatosis patients after combined chemoradiation therapy.) [dissertation] Moscow; 2008. 122 p. (In Russ)]
  9. Philippova MM, Khachin DP, Sazonova OV, et al. Fragments of functional proteins in a primary culture of human erythrocytes. Russ J Bioorg Chem. 2008;34(2):145–55. doi: 10.1134/S1068162008020027.
  10. Pivnik AV, Rasstrigin NA, Philippova MM, et al. Alteration of Intraerythrocyte Proteolytic Degradation of Hemoglobin During Hodgkin’s Disease. Leuk Lymphoma. 1996;22(3–4):345–9. doi: 10.3109/10428199609051767.
  11. Непомнящая Н.И. Психологический аспект онкологических заболеваний. Психологический журнал. 1998;4:132–45.
    [Nepomnyashchaya NI. The psychological aspect of oncological diseases. Psikhologicheskii zhurnal. 1998;4:132–45. (In Russ)]
  12. Расстригин Н.А. Альтернирующая полихимиотерапия лимфогранулематоза: Дис. … канд. мед. наук. М., 1999. 124 с.
    [Rasstrigin NA. Alterniruyushchaya polikhimioterapiya limfogranulematoza. (Alternating polychemotherapy of lymphogranulomatosis.) [dissertation] Moscow; 1999. 124 p. (In Russ)]
  13. Асланиди И.П., Мухортова О.В., Катунина Т.А. и др. Современные аспекты применения позитронно-эмиссионной томографии при лимфомах. Клиническая онкогематология. 2015;8(1):13–25. doi: 10.21320/2500-2139-2015-8-1-13-25.
    [Aslanidi IP, Mukhortova OV, Katunina TA, et al. Positron Emission Tomography in Modern Management of Lymphomas. Clinical oncohematology. 2015;8(1):13–25. doi: 10.21320/2500-2139-2015-8-1-13-25. (In Russ)]
  14. Khamaganova E, Aleschenko S, Murashova L, Zaretskaya Y. Immunogenetic factors of predisposition to blood malignancies in Russian population. Russ J Immunol. 2001;6(3):265–70.
  15. Swerdlow SH, Campo E, Pileri SA. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. 2016;127(20):2375–90. doi: 10.1182/blood-2016-01-643569.
  16. The Nobel Prize. Available from: https://www.nobelprize.org/prizes/medicine/2008/press-release/ (accessed 27.10.2020).
  17. ЮНЭЙДС. COVID-19 и ВИЧ [электронный документ]. Доступно по: https://www.unaids.org/ru. Ссылка активна на 10.2020.
    [UNAIDS. COVID-19 and HIV. [Internet] Available from: https://www.unaids.org/ru. (accessed 27.10.2020) (In Russ)]
  18. ВИЧ-инфекция и СПИД: национальное руководство. Под ред. В.В. Покровского. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2020. 696 с. doi: 10.33029/9704-5421-3-2020-VIC-1-696.
    [Pokrovsky VV, ed. VICh-infektsiya i SPID: natsionalnoe rukovodstvo. (HIV infection and AIDS: Federal Guidelines.) 2nd edition, revised and enlarged. Moscow: GEOTAR-Media Publ.; 2020. 696 p. doi: 10.33029/9704-5421-3-2020-VIC-1-696. (In Russ)]
  19. Barre-Sinoussi F, Ross AL, Delfraissy JF. Past, present and future: 30 years of HIV research. Nat Rev Micr 2013;11(12):877–83. doi: 10.1038/nrmicro3132.
  20. Lu DY, Wu HY, Yarla NS, et al. HAART in HIV/AIDS Treatments: Future Trends. Infect Disord Drug Targ. 2018;18(1):15–22. doi: 10.2174/1871526517666170505122800.
  21. Brown I am the Berlin patient: a personal reflection. AIDS Res Hum Retrovir. 2015;31(1):2–3. doi: 10.1089/AID.2014.0224.
  22. Gallagher Berlin patient: First person cured of HIV, Timothy Ray Brown, dies. Available from: https://www.bbc.com/news/health-54355673. (accessed 27.10.2020).
  23. Пивник А.В., Туманова М.В., Чистякова А.В. и др. Анализ стационарной помощи инфицированным ВИЧ больным злокачественными лимфомами и гепатитами за 5 лет (2011–2015 гг.) в МКНЦ им. А.С. Логинова ДЗМ. Терапевтический архив. 2017;89(7):105–11. doi: 10.17116/terarkh2017897105-111.
    [Pivnik AV, Tumanova MV, Chistyakova AV, et al. Analysis of inpatient care for HIV-positive patients with malignant lymphomas and hepatitis over 5 years (2011–2015) at the A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department. Terapevticheskii arkhiv. 2017;89(7):105–11. doi: 10.17116/terarkh2017897105-111. (In Russ)]
  24. Lucas S, Nelson AM. HIV and the spectrum of human disease. J Pathol. 2015;235(2):229–41. doi: 1002/path.4449.
  25. Hosoda T, Uehara Y, Kasuga T, et al. An HIV-infected patient with acute retinal necrosis as immune reconstitution inflammatory syndrome due to varicella-zoster virus. AIDS. 2020;34(5):795–6. doi: 10.1097/QAD.0000000000002477.
  26. Namale PE, Abdullahi LH, Fine S. Paradoxical TB-IRIS in HIV-infected adults: a systematic review and meta-analysis. Fut Microbiol. 2015;10(6):1077–99. doi: 10.2217/fmb.15.9.
  27. Пивник А.В., Туманова М.В., Серегин Н.В. и др. Лимфомы у ВИЧ-инфицированных больных: обзор литературы. Клиническая онкогематология. 2014;7(3):264–77.
    [Pivnik AV, Tumanova MV, Seregin NV, et al. Lymphomas in HIV­Infected Patients: Literature Review. Klinicheskaya onkogematologiya. 2014;7(3):264–77. (In Russ)]
  28. Лейгтон Р.А., ПивникА.В., Сергеева Е.П. и др. Плазмоклеточные опухоли у ВИЧ-инфицированных пациентов (обзор литературы и собственные наблюдения). Клиническая онкогематология. 2017;10(4):464–70. doi: 10.21320/2500-2139-2017-10-4-464-470.
    [Leigton RA, Pivnik AV, Sergeeva EP, et al. Plasma cell neoplasms in HIV-Infected Patients: A Literature Review and Case Series. Clinical oncohematology. 2017;10(4):464–70. doi: 10.21320/2500-2139-2017-10-4-464-470. (In Russ)]

Checkpoint Inhibitors and Classical Hodgkin’s Lymphoma: Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Tumor (Experience at the NI Pirogov Russian National Medical Center of Surgery)

AUTOIMMUNE THROMBOCYTOPENIA ,

VO Sarzhevskii, EA Demina, NE Mochkin, AA Spornik, AA Mamedova, EG Smirnova, AE Bannikova, AA Samoilova, VS Bogatyrev, VYa Melnichenko

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Prof. Vladislav Olegovich Sarzhevskii, MD, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: +7(495)603-72-17; e-mail: vladsar100@gmail.com

For citation: Sarzhevskii VO, Demina EA, Mochkin NE, et al. Checkpoint Inhibitors and Classical Hodgkin’s Lymphoma: Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Tumor (Experience at the NI Pirogov Russian National Medical Center of Surgery). Clinical oncohematology. 2021;14(1):53–62. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-53-62

ABSTRACT

Background. Checkpoint inhibitors contribute to improving the treatment outcomes in patients with relapsed/refractory classical Hodgkin’s lymphoma (cHL). The paper describes the first generalized experience with pembrolizumab-inducing cHL immunotherapy in Russia. The hallmark of the study is a long follow-up period.

Aim. To retrospectively assess efficacy and safety of pembrolizumab-inducing immunotherapy of relapsed/refractory cHL.

Materials & Methods. The study enrolled 14 cHL patients: 3 men and 11 women aged 24–57 years (median 33 years). Pembrolizumab 200 mg or 2 mg/kg was intravenously administered every 3 weeks. Median pembrolizumab administration number was 27 (max. 52 administrations), median follow-up after immunotherapy onset was 31 months.

Results. Complete response (as best response) was achieved in 8 (57 %) patients, 3 (21 %) patients showed partial response (as best response). Overall objective response was 78 %. Median number of pembrolizumab administrations resulting in better responses to immunotherapy was 4, which corresponded to 3 months of treatment. Maximum number of pembrolizumab administrations before achieving best response was 32. Best response duration (the period from achieving it to disease progression/relapse or to the end-point of data collection in case of sustained response) varied from 3 to 56 months (median 15 months). Most common severe adverse events of grade 3–4 were pulmonary complications. Overall survival for 12, 24, and 36 months was 92.9 %, 85.7 %, and 85.7 %, respectively, and progression-free survival was 76.9 %, 59.3 %, and 37.1 %, respectively; median time before progression was 27.7 months.

Conclusion. The experience with pembrolizumab-inducing immunotherapy of relapsed/refractory cHL in Russia proves the efficacy and relative safety of this treatment approach. Due to long follow-up period a series of crucial practical immunotherapy-related issues were raised, which will need to be dealt with in future studies.

Keywords: сheckpoint inhibitors, immunotherapy, classical Hodgkin’s lymphoma, pembrolizumab.

Received: September 7, 2020

Accepted: December 2, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Ansell S, Lesokhin A, Borrello I, et al. PD-1 Blockade With Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. N Engl J Med. 2015;372(4):311–9. doi: 10.1056/NEJMoa1411087.
  2. Armand P, Engert A, Younes A, et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018;36(14):1428–39. doi: 10.1200/JCO.2017.76.0793.
  3. Armand P, Shipp MA, Ribrag V, et al. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016;34(31):3733–9. doi: 10.1200/JCO.2016.67.3467.
  4. Chen R, Zinzani P, Fanale M, et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017;35(19):2125–32. doi: 10.1200/JCO.2016.72.1316.
  5. Zinzani P, Lee H, Armand P, et al. Three-Year Follow-up of Keynote-087: Pembrolizumab Monotherapy in Relapsed/Refractory Classic Hodgkin Lymphoma. 2019;134(Suppl_1):240. doi: 10.1182/blood-2019-127280.
  6. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/JCO.2013.54.8800.
  7. Cheson BD, Ansell S, Schwartz L, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128(21):2489–96. doi: 10.1182/blood-2016-05-718528.
  8. Younes A, Hilden P, Coiffier B, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann 2017;28(7):1436–47. doi: 10.1093/annonc/mdx097.
  9. Лепик К.В. Эффективность и безопасность PD-1 ингибитора (ниволумаба) в лечении резистентной и рецидивирующей лимфомы Ходжкина: Автореф. дис. … канд. мед. наук. СПб., 2019.
    [Lepik KV. Effektivnost i bezopasnost PD-1 ingibitora (nivolumaba) v lechenii rezistentnoi i retsidiviruyushchei limfomy Khodzhkina. (Efficacy and safety of PD-1 inhibitor (nivolumab) in the treatment of relapsed/refractory Hodgkin’s lymphoma.) [dissertation] Saint Petersburg; 2019. (In Russ)]
  10. Mokrane F-Z, Chen A, Schwartz LH, et al. Performance of CT Compared with 18F-FDG PET in Predicting the Efficacy of Nivolumab in Relapsed or Refractory Hodgkin Lymphoma. Radiology. 2020;295(3):651–61. doi: 10.1148/radiol.2020192056.
  11. Ansell S, Armand Р, Timmerman J, et al. Nivolumab re-treatment in patients with relapsed/refractory Hodgkin lymphoma: safety and efficacy outcomes from a phase 1 clinical trial. Poster presentation at the 10th International Symposium on Hodgkin Lymphoma (ISHL); October 22–25, 2016; Cologne, Germany. Abstract 583/P090.
  12. Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: Two-year follow-up of KEYNOTE-087. Blood. 2019;134(14):114–53. doi: 10.1182/blood.2019000324.
  13. Manson G, Brice P, Herbaux C, et al. Efficacy of anti-PD1 Re-Treatment in Patients With Hodgkin Lymphoma Who Relapsed After anti-PD1 Discontinuation. Haematologica. 2020;105. [Epub ahead of print] doi: 10.3324/haematol.2019.242529.
  14. Armand P, Kuruvilla J, Michot J-M, et al. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv. 2020;4(12):2617–22. doi: 10.1182/bloodadvances.2019001367.
  15. Domingo-Domenech E, Sureda А. Treatment of Hodgkin Lymphoma Relapsed after Autologous Stem Cell Transplantation. J Clin Med. 2020;9(5):1384. doi: 10.3390/jcm9051384.

Ph-Negative Myeloproliferative Neoplasms: Diagnosis and Treatment Challenges in Russia (the Case of Saint Petersburg)

AUTOIMMUNE THROMBOCYTOPENIA , ,

MO Ivanova, EV Morozova, MV Barabanshchikova, BV Afanasyev

IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Mariya Olegovna Ivanova, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: marilexo@yandex.ru

For citation: Ivanova MO, Morozova EV, Barabanshchikova MV, Afanasyev BV. Ph-Negative Myeloproliferative Neoplasms: Diagnosis and Treatment Challenges in Russia (the Case of Saint Petersburg). Clinical oncohematology. 2021;14(1):45–52. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-45-52

ABSTRACT

Ph-negative myeloproliferative neoplasms (MPN) are rare oncohematological diseases characterized by long duration and indolence. World epidemiological data on these diseases considerably vary depending on geographical area and time frame of the study. The breakthrough in the understanding of MPN pathogenesis, observed in the early 2000s, enabled to elaborate approaches to differential diagnosis and treatment of Ph-negative MPNs as well as to improve their prognosis. Although these approaches are specified in the Russian clinical guidelines, physicians still face challenges in their implementation in practice. The present review provides a detailed description and analysis of literature data on epidemiology, pathogenesis, and principles of Ph-negative MPN diagnosis and treatment. It also describes the situation in Saint Petersburg as an example of existing challenges in management of patients with Ph-negative MPNs in Russia and offers potential solutions.

Keywords: myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, primary myelofibrosis.

Received: August 13, 2020

Accepted: November 29, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006;355(23):2452–66. doi: 10.1056/NEJMra063728.
  2. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544.
  3. Adamson JW, Fialkow PJ, Murphy S, et al. Polycythemia Vera: Stem-Cell and Probable Clonal Origin of the Disease. N Engl J Med. 1976;295(17):913–6. doi: 10.1056/NEJM197610212951702.
  4. Titmarsh GJ, Duncombe AS, Mcmullin MF, et al. How common are myeloproliferative neoplasms? A systematic review and meta-analysis. Am J Hematol. 2014;89(6):581–7. doi: 10.1002/ajh.23690.
  5. Deadmond MA, Smith-Gagen JA. Changing incidence of myeloproliferative neoplasms: trends and subgroup risk profiles in the USA, 1973–2011. J Cancer Res Clin Oncol. 2015;141(12):2131–8. doi: 10.1007/s00432-015-1983-5.
  6. Moulard O, Mehta J, Fryzek J, et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. Eur J Haematol. 2014;92(4):289–97. doi: 10.1111/ejh.12256.
  7. Byun JM, Kim YJ, Youk T, et al. Real world epidemiology of myeloproliferative neoplasms: a population based study in Korea 2004–2013. Ann Hematol. 2017;96(3):373–81. doi: 10.1007/s00277-016-2902-9.
  8. Mehta J, Wang H, Iqbal SU, Mesa R. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma. 2014;55(3):595–600. doi: 10.3109/10428194.2013.813500.
  9. Shuvaev V, Martynkevich I, Abdulkadyrova A, et al. Ph-Negative Chronic Myeloproliferative Neoplasms – Population Analysis, a Single Center 10-years’ Experience. Blood. 2014;124(21):5556. doi: 10.1182/blood.v124.21.5556.5556.
  10. Федеральный закон от 21 ноября 2011 г. № 323-ФЗ «Об основах охраны здоровья граждан в Российской Федерации» [электронный документ]. Доступно по: https://minzdrav.gov.ru/documents/7025-federalnyy-zakon-323-fz-ot-21-noyabrya-2011-g. Ссылка активна на10.2020.
    [Federal Law of November 21, 2011 No. 323-FZ “On the fundamentals of public health protection in the Russian Federation”. [Internet] Available from: https://minzdrav.gov.ru/documents/7025-federalnyy-zakon-323-fz-ot-21-noyabrya-2011-g. (accessed 21.10.2020) (In Russ)]
  11. Schischlik F, Kralovics R. Mutations in myeloproliferative neoplasms–their significance and clinical use. Expert Rev Hematol. 2017;10(11):961–73. doi: 10.1080/17474086.2017.1380515.
  12. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779–90. doi: 10.1056/NEJMoa051113.
  13. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97. doi: 10.1016/j.ccr.2005.03.023.
  14. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61. doi: 10.1016/s0140-6736(05)71142-9.
  15. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8. doi: 10.1038/nature03546.
  16. Scott LM. The JAK2 exon 12 mutations: A comprehensive review. Am J Hematol. 2011;86(8):668–76. doi: 10.1002/ajh.22063.
  17. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):1140–51. doi: 10.1371/journal.pmed.0030270.
  18. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients. Blood. 2006;108(10):3472–6. doi: 10.1182/blood-2006-04-018879.
  19. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90. doi: 10.1056/NEJMoa1311347.
  20. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405. doi: 10.1056/NEJMoa1312542.
  21. Harrison CN, Vannucchi AM. Closing the gap: Genetic landscape of MPN. Blood. 2016;127(3):276–8. doi: 10.1182/blood-2015-10-674101.
  22. Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15. doi: 10.1038/s41408-018-0054-y.
  23. Меликян А.Л., Ковригина А.М., Суборцева И.Н. и др. Ph-негативные миелопролиферативные заболевания. Клинические рекомендации. 2018 г. [электронный документ]. Доступно по: http://cr.rosminzdrav.ru/#!/recomend/96. Ссылка активна на 21.10.2020.
    [Melikyan AL, Kovrigina AM, Subortseva IN, et al. Ph-negative myeloproliferative neoplasms. Clinical guidelines. 2018. [Internet] Available from: http://cr.rosminzdrav.ru/#!/recomend/96. (accessed 21.10.2020) (In Russ)]
  24. Tefferi A. Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93(12):1551–60. doi: 10.1002/ajh.25230.
  25. Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013;27(9):1861–9. doi: 10.1038/leu.2013.119.
  26. Vannucchi AM, Guglielmelli P, Rotunno G, et al. Mutation-Enhanced International Prognostic Scoring System (MIPSS) for Primary Myelofibrosis: An AGIMM & IWG-MRT Project. Blood. 2014;124(21):405. doi: 10.1182/blood.v124.21.405.405.
  27. Barbui T, Tefferi A, Vannucchi AM, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet HHS Public Access. Leukemia. 2018;32(5):1057–69. doi: 10.1038/s41375-018-0077-1.
  28. NCCN Clinical Practice Guidelines in Oncology. Myeloproliferative Neoplasms. Version 2.2017. Available from: https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf (accessed 11.2020).
  29. Vannucchi AM, Barbui T, Cervantes F, et al. Philadelphia Chromosome-Negative Chronic Myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v85–v99. doi: 10.1093/annonc/mdv203.
  30. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera. N Engl J Med. 2015;372(5):426–35. doi: 10.1056/NEJMoa1409002.
  31. Griesshammer M, Saydam G, Palandri F, et al. Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial. Ann Hematol. 2018;97(9):1591–600. doi: 10.1007/s00277-018-3365-y.
  32. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. 2014;120(4):513–20. doi: 10.1002/cncr.28441.
  33. Распоряжение Правительства Российской Федерации от 12 октября 2019 г. № 2406-р [электронный документ]. Доступно по: http://static.government.ru/media/files/K1fPEUszF2gmvwTkw74iPOASarj7KggI.pdf. Ссылка активна на 21.10.2020.
    [Russian Federation government resolution of October 12, 2019 No. 2406-r. [Internet] Available from: http://static.government.ru/media/files/K1fPEUszF2gmvwTkw74iPOASarj7KggI.pdf. (accessed 10.2020) (In Russ)]
  34. Постановление Правительства РФ от 26 апреля 2012 г. № 403 «О порядке ведения Федерального регистра лиц, страдающих жизнеугрожающими и хроническими прогрессирующими редкими (орфанными) заболеваниями, приводящими к сокращению продолжительности жизни граждан или их инвалидности, и его регионального сегмента» (с изменениями и дополнениями) [электронный документ]. Доступно по: http://base.garant.ru/70168888/. Ссылка активна на 21.10.2020.
    [Russian Federation government decree of April 26, 2012 No. 403 “On the rules for Federal Register of persons with life-threatening and chronic progressive rare (orphan) diseases leading to the reduction in life expectancy or disability, and its regional segment” (amended and revised.) [Internet] Available from: http://base.garant.ru/70168888/. (accessed 10.2020) (In Russ)]

Gynecological Myeloid Sarcoma: Literature Review and a Case Report

AUTOIMMUNE THROMBOCYTOPENIA

AA Shatilova1, LL Girshova1, DV Zaitsev1, IG Budaeva1, YuV Mirolyubova1, DV Ryzhkova1, RV Grozov1, KV Bogdanov1, TS Nikulina1, DV Motorin1, DB Zammoeva1, SV Efremova1, VV Ivanov1, AV Petukhov1,2, YuA Alekseeva1, AYu Zaritskey1

1 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

2 Institute of Cytology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064

For correspondence: Aleksina Alekseevna Shatilova, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(911)476-35-58; e-mail: alexina-96@list.ru

For citation: Shatilova AA, Girshova LL, Zaitsev DV, et al. Gynecological Myeloid Sarcoma: Literature Review and a Case Report. Clinical oncohematology. 2021;14(1):31–44. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-31-44

ABSTRACT

Myeloid sarcoma, also known as chloroma or granulocytic sarcoma, is a rare disease characterized by the proliferation of immature myeloid cells in extramedullary lesions. Chloroma is more commonly observed in patients with acute myeloid leukemias, other myeloproliferative neoplasms, or myelodysplastic syndrome. However, it can also manifest itself as solitary tumor. Sarcoma can develop in different organs and tissues, but most frequently it appears in lymph nodes, soft tissues, and bones. Myeloid sarcoma with primary gynecological lesion is very rarely mentioned. In literature cases of cervical lesions are described. The present article summarizes the literature data concerning different aspects of myeloid sarcoma diagnosis and treatment. The issue under discussion is the role of chemotherapy, radiotherapy, surgery, and bone marrow transplantation in the treatment of this malignant tumor. It appears that whatever the primary tumor localization, the best treatment options are chemotherapy and allogeneic bone marrow transplantation (allo-BMT). A promising trend is the use of novel targeted drugs improving outcomes of treatment. The article provides a case report of a female patient with cervical myeloid sarcoma and concomitant bone marrow involvement, as well as the description of clinical course, diagnosis, and treatment. The patient received chemotherapy with subsequent allo-BMT. The pre-transplant therapy enabled allo-BMT with the deepest response possible. The patient achieved PET- and MRD-negative complete remission of cervical myeloid sarcoma and bone marrow.

Keywords: cervical myeloid sarcoma, gynecologic tract, acute myeloid leukemias.

Received: August 12, 2020

Accepted: December 4, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена, 2019. С. 10, 34, 125.
    [Kaprin AD, Starinskii VV, Petrova GV, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2018 godu (zabolevaemost i smertnost). (Malignant neoplasms in Russia in 2018: incidence and mortality.) Moscow: MNIOI im. P.A. Gertsena Publ.; 2019. pp. 10, 34, 125. (In Russ)]
  2. Michelle SР, Karen JK, Ursula AM. Gynecologic Tumors and Malignancies. In: Atlas of Diagnostic Oncology. 4th edition. Philadelphia: Mosby Elsevier; рр. 278–324.
  3. Онкогинекология: национальное руководство. Под ред. А.А. Каприна. М.: ГЭОТАР-Медиа, 2019. С. 27–31, 114–115, 161.
    [Kaprin AD, ed. Onkoginekologiya: natsionalnoe rukovodstvo. (Oncogynecology: national guide.) Moscow: GEOTAR-Media Publ.; 2019. pp. 27–31, 114–115, 161. (In Russ)]
  4. Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO Classification of Tumours of Female Reproductive Organs. Lyon: IARC Press; 2014.
  5. Almond L, Charalampakis M, Ford S, et al. Myeloid Sarcoma: Presentation, Diagnosis, and Treatment. Clin Lymphoma Myel Leuk. 2017;17(5):263–7. doi: 10.1016/j.clml.2017.02.027.
  6. Swerdlow SH. WHO Classification Of Tumours Of Haematopoietic And Lymphoid Tissues. Lyon: IARC Press; 2017. рр. 167–8.
  7. Kawamoto K, Miyoshi H, Yoshida N, et al. Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients. Am J Surg Pathol. 2016;40(11):1473–83. doi: 10.1097/PAS.0000000000000727.
  8. Campidelli C, Agostinelli C, Stitson R, et al. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol. 2009;132(3):426–37. doi: 10.1309/AJCP1ZA7HYZKAZHS.
  9. Byrd JC, Edenfield WJ, Shields DJ, et al. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol. 1995;13(7):1800–16. doi: 10.1200/JCO.1995.13.7.1800.
  10. Goyal G, Bartley AC, Patnaik MM, et al. Clinical features and outcomes of extramedullary myeloid sarcoma in the United States: analysis using a national data set. Blood Cancer J. 2017;7(8):e592. doi: 10.1038/bcj.2017.79.
  11. Bakst RL, Tallman MS, Douer D, et al. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118(14):3785–93. doi: 10.1182/blood-2011-04-347229.
  12. Shahin O, Ravandi F. Myeloid sarcoma. Curr Opin Hematol. 2020;27(2):88–94. doi: 10.1097/moh.0000000000000571.
  13. Avni B, Koren-Michowitz M. Myeloid sarcoma: current approach and therapeutic options. Ther Adv Hematol. 2011;2(5):309–16. doi: 10.1177/2040620711410774.
  14. Claerhout H, Van Aelst S, Melis C, et al. Clinicopathological characteristics of de novo and secondary myeloid sarcoma: A monocentric retrospective study. Eur J Haematol. 2018;100(6):603–12. doi: 10.1111/ejh.13056.
  15. Pathak B, Bruchim I, Brisson ML, et al. Granulocytic sarcoma presenting as tumors of the cervix. Gynecol Oncol. 2005;98(3):493–7. doi: 10.1016/j.ygyno.2005.04.028.
  16. Gui W, Li J, Zhang Z, et al. Primary hematological malignancy of the uterine cervix: A case report. Oncol Lett. 2019;18(3):3337–41. doi: 10.3892/ol.2019.10652.
  17. Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21(2):340–50. doi: 10.1038/sj.leu.2404491.
  18. Sharma V, Dora T, Patel M, et al. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India. Case Rep Hematol. 2016;2016:1–4. doi: 10.1155/2016/3042531.
  19. Lee J, Kim Y, Min Y, et al. Granulocytic sarcoma of the uterine cervix. Int J Gynecol Cancer. 2004;14(3):553–7. doi: 10.1111/j.1048-891x.2004.014321.x.
  20. Yu Y, Qin X, Yan S, et al. Non-leukemic myeloid sarcoma involving the vulva, vagina, and cervix: a case report and literature review. Onco Targets Ther. 2015;8:3707–13. doi: 10.2147/OTT.S92815.
  21. Kaur V, Swami A, Alapat D, et al. Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years. Hematology. 2018;23(1):17–24. doi: 10.1080/10245332.2017.1333275.
  22. Kashofer K, Gornicec M, Lind K, et al. Detection of prognostically relevant mutations and translocations in myeloid sarcoma by next generation sequencing. Leuk Lymphoma. 2018;59(2):501–4. doi: 10.1080/10428194.2017.1339879.
  23. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-235358.
  24. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Клинические рекомендации российских экспертов по лечению больных острыми миелоидными лейкозами в возрасте моложе 60 лет. Терапевтический архив. 2014;86(7):4–13.
    [Savchenko VG, Parovichnikova EN, Afanasyev BV, et al. Russian experts’ clinical guidelines for acute myeloid leukemia treatment in patients less than 60 years of age. Terapevticheskii arkhiv. 2014;86(7):4–13. (In Russ)]
  25. Гиршова Л.Л., БудаеваИ.Г., Овсянникова Е.Г. и др. Прогностическое значение и корреляция динамики гиперэкспрессии гена WT1 и мутации гена NPM1 у пациентов с острым миелобластным лейкозом. Клиническая онкогематология. 2017;10(4):485–93. doi: 10.21320/2500-2139-2017-10-4-485-493.
    [Girshova LL, Budaeva IG, Ovsyannikova EG, et al. Prognostic Value and Correlation Between WT1 Overexpression and NPM1 Mutation in Patients with Acute Myeloblastic Leukemia. Clinical oncohematology. 2017;10(4):485–93. doi: 10.21320/2500-2139-2017-10-4-485-493. (In Russ)]
  26. Adams HJ, Kwee TC. Prognostic value of pretransplant FDG-PET in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation: systematic review and meta-analysis. Ann Hematol. 2016;95(5):695–706. doi: 10.1007/s00277-016-2619-9.
  27. Aschoff P, Hantschel M, Oksuz M, et al. Integrated FDG-PET/CT for detection, therapy monitoring and follow-up of granulocytic sarcoma. Initial results. Nuklearmedizin. 2009;48(5):185–91. doi: 10.3413/nukmed-0236.
  28. NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 3.2020. Available from: https://www.nccn.org/professionals/physician_gls/pdf/aml_blocks.pdf. (accessed 12.11.2020).
  29. Kahn RM, Gordhandas S, Chapman-Davis E, et al. Acute Myeloid Leukemia Presenting as Myeloid Sarcoma with a Predisposition to the Gynecologic Tract. Case Rep Oncol Med. 2019;2019:1–5. doi: 10.1155/2019/4189275.
  30. Modi G, Madabhavi I, Panchal H, et al. Primary vaginal myeloid sarcoma: a rare case report and review of the literature. Case Rep Obstet Gynecol. 2015;2015:1–4. doi: 10.1155/2015/957490.
  31. Hernandez J-A, Navarro J-T, Rozman M, et al. Primary myeloid sarcoma of the gynecologic tract: a report of two cases progressing to acute myeloid leukemia. Leuk Lymphoma. 2002;43(11):2151–3. doi: 10.1080/1042819021000016096.
  32. Ucar M, Guryildirim M. Granulocytic Sarcoma of the Uterus: A Rare Presentation of Extramedullary Relapse of AML and Importance of MRI. Case Rep Radiol. 2014;2014:1–4. doi: 10.1155/2014/501342.
  33. Garcia MG, Deavers MT, Knoblock RJ, et al. Myeloid sarcoma involving the gynecologic tract: a report of 11 cases and review of the literature. Am J Clin Pathol. 2006;125(5):783–90. doi: 10.1309/H9MM-21FP-T7YB-L3PW.
  34. Kim SCН, Natarajan-Ame S, Lioure B, et al. Successful treatment of a granulocytic sarcoma of the uterine cervix in complete remission at six-year follow-up. J Oncol. 2010;2010:1–3. doi: 10.1155/2010/812424.
  35. Gill H, Loong F, Mak V, et al. Myeloid sarcoma of the uterine cervix presenting as missed abortion. Arch Gynecol Obstet. 2012;286(5):1339–41. doi: 10.1007/s00404-012-2454-8.
  36. Weingertner AS, Wilt M, Atallah I, et al. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature. Case Rep Oncol. 2009;2(1):1–6. doi: 10.1159/000191215.
  37. Bao H, Gao J, Chen YH, et al. Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass. Diagn Pathol. 2019;14(1):26. doi: 10.1186/s13000-019-0804-6.
  38. Otoukesh S, Zhang J, Nakamura R, et al. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement. Leuk Lymphoma. 2020;61(8):2020–3. doi: 10.1080/10428194.2020.1742908.
  39. Kanate AS, Vos J, Chargualaf MJ. Venetoclax for Refractory Myeloid Sarcoma. J Oncol Pract. 2019;15(7):413–5. doi: 10.1200/JOP.18.00753.
  40. Girshova L, Romanova E, Kholopova I, et al. Isolated Myeloid Sarcoma Involving the Breast. Blood. 2012;120(21):4345. doi: 10.1182/blood.v120.21.4345.4345.
  41. Chevallier P, Labopin M, Cornelissen J, et al. Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation. Haematologica. 2011;96(9):1391–4. doi: 10.3324/haematol.2011.041418.
  42. Lachowiez C, DiNardo CD, Konopleva M. Venetoclax in acute myeloid leukemia – current and future directions. Leuk Lymphoma. 2020;61(6):1313–22. doi: 10.1080/10428194.2020.1719098.
  43. Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981;48(6):1426–37. doi: 10.1002/1097-0142(19810915)48:6<1426::aid-cncr2820480626>3.0.co;2-g.
  44. Meyer HJ, Ponisch W, Schmidt SA, et al. Clinical and imaging features of myeloid sarcoma: a German multicenter study. BMC Cancer. 2019;19(1):1150. doi: 10.1186/s12885-019-6357-y.
  45. Wang HQ, Li J. Clinicopathological features of myeloid sarcoma: Report of 39 cases and literature review. Pathol Res Pract. 2016;212(9):817–24. doi: 10.1016/j.prp.2016.06.014.