chemotherapy

Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

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

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail: sychevskaya-ka@yandex.ru

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219

ABSTRACT

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

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Статистика Plumx английский

REFERENCES

  1. Foley C, Mackey MC. Dynamic hematological disease: a review. J Math Biol. 2009;58(1–2):285–322. doi: 10.1007/s00285-008-0165-3.
  2. Morley AA. A neutrophil cycle in healthy individuals. Lancet. 1966;2(7475):1220–2. doi: 10.1016/s0140-6736(66)92303-8.
  3. Mackey MC, Glass L. Oscillation and chaos in physiological control systems. Science. 1977;197(4300):287–9. doi: 10.1126/science.267326.
  4. Mackey Cell kinetic status of haematopoietic stem cells. Cell Prolif. 2001;34(2):71–83. doi: 10.1046/j.1365-2184.2001.00195.x.
  5. Pujo-Menjouet L, Mackey MC. Contribution to the study of periodic chronic myelogenous leukemia. Compt Rend Biol. 2004;327(3):235–44. doi: 10.1016/j.crvi.2003.05.004.
  6. Schirm S, Engel C, Loeffler M, Scholz M. Modelling chemotherapy effects on granulopoiesis. BMC Syst Biol. 2014;8(1):138. doi: 10.1186/s12918-014-0138-7.
  7. Dale DC, Bolyard AA, Aprikyan A. Cyclic neutropenia. Semin Hematol. 2002;39(2):89–94. doi: 10.1053/shem.2002.31917.
  8. Levy EJ, Schetman D. Cyclic neutropenia. Arch Dermatol. 1961;84(3):429–33. doi: 10.1001/archderm.1961.01580150075012.
  9. Colijn C, Mackey MC. A mathematical model of hematopoiesis: II. Cyclical neutropenia. J Theor Biol. 2005;237(2):133–46. doi: 10.1016/j.jtbi.2005.03.034.
  10. Horwitz M, Benson KF, Person RE, et al. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999;23(4):433–6. doi: 10.1038/70544.
  11. Aprikyan AA, Liles WC, Rodger E, et al. Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia. Blood. 2001;97(1):147–53. doi: 10.1182/blood.v97.1.147.
  12. Horwitz MS, Corey SJ, Grimes HL, Tidwell T. ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematol Oncol Clin N Am. 2013;27(1):19-vii. doi: 10.1016/j.hoc.2012.10.004.
  13. Welte K, Zeidler C, Dale DC. Severe congenital neutropenia. Semin Hematol. 2006;43(3):189–95. doi: 10.1053/j.seminhematol.2006.04.004.
  14. Haurie C, Dale DC, Rudnicki R, Mackey MC. Modeling complex neutrophil dynamics in the grey collie. J Theor Biol. 2000;204(4):505–19. doi: 10.1006/jtbi.2000.2034.
  15. Horwitz MS, Duan Z, Korkmaz B, et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood. 2007;109(5):1817–24. doi: 10.1182/blood-2006-08-019166.
  16. Go RS. Idiopathic cyclic thrombocytopenia. Blood Rev. 2005;19(1):53–9. doi: 10.1016/j.blre.2004.05.001.
  17. Zhuge C, Mackey MC, Lei J. Origins of oscillation patterns in cyclical thrombocytopenia. J Theor Biol. 2019;462:432–45. doi: 10.1016/j.jtbi.2018.11.024.
  18. Apostu R, Mackey MC. Understanding cyclical thrombocytopenia: a mathematical modeling approach. J Theor Biol. 2008;251(2):297–316. doi: 10.1016/j.jtbi.2007.11.029.
  19. Colijn C, Mackey MC. A mathematical model of hematopoiesis–I. Periodic chronic myelogenous leukemia. J Theor Biol. 2005;237(2):117–32. doi: 10.1016/j.jtbi.2005.03.033.
  20. Fortin P, Mackey MC. Periodic chronic myelogenous leukaemia: spectral analysis of blood cell counts and aetiological implications. Br J Haematol. 1999;104(2):336–45. doi: 10.1046/j.1365-2141.1999.01168.x.
  21. Morley A, Stohlman F Jr. Cyclophosphamide-induced cyclical neutropenia. An animal model of a human periodic disease. N Engl J Med. 1970;282(12):643–6. doi: 10.1056/NEJM197003192821202.
  22. Kennedy Cyclic leukocyte oscillations in chronic myelogenous leukemia during hydroxyurea therapy. Blood. 1970;35(6):751–60. doi: 10.1182/blood.v35.6.751.751.
  23. Zhuge C, Lei J, Mackey MC. Neutrophil dynamics in response to chemotherapy and G-CSF. J Theor Biol. 2012;293:111–20. doi: 10.1016/j.jtbi.2011.10.017.
  24. Price TH, Chatta GS, Dale DC. Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood. 1996;88(1):335–40. doi: 10.1182/blood.V88.1.335.335.
  25. Chatta GS, Price TH, Allen RC, Dale DC. Effects of in vivo recombinant methionyl human granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers. Blood. 1994;84(9):2923–9. doi: 10.1182/blood.V84.9.2923.2923.
  26. Dancey JT, Deubelbeiss KA, Harker LA, Finch CA. Neutrophil kinetics in man. J Clin Invest. 1976;58(3):705–15. doi: 10.1172/JCI108517.
  27. Kerrigan DP, Castillo A, Foucar K, et al. Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration. Am J Clin Pathol. 1989;92(3):280–5. doi: 10.1093/ajcp/92.3.280.
  28. Hakansson L, Hoglund M, Jonsson UB, et al. Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion. Br J Haematol. 1997;98(3):603–11. doi: 10.1046/j.1365-2141.1997.2723093.x.
  29. Ohsaka A, Saionji K, Sato N, et al. Granulocyte colony-stimulating factor down-regulates the surface expression of the human leucocyte adhesion molecule-1 on human neutrophils in vitro and in vivo. Br J Haematol. 1993;84(4):574–80. doi: 10.1111/j.1365-2141.1993.tb03130.x.
  30. Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in Neutropenia. J Immunol. 2015;195(4):1341–9. doi: 10.4049/jimmunol.1500861.
  31. Dale DC, Bonilla MA, Davis MW, et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood. 1993;81(10):2496–502. doi: 10.1182/blood.V81.10.2496.2496.
  32. Shinjo K, Takeshita A, Ohnishi K, Ohno R. Granulocyte colony-stimulating factor receptor at various differentiation stages of normal and leukemic hematopoietic cells. Leuk Lymphoma. 1997;25(1–2):37–46. doi: 10.3109/10428199709042494.
  33. Clark OA, Lyman GH, Castro AA, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol. 2005;23(18):4198–214. doi: 10.1200/JCO.2005.05.645.
  34. Garcia-Carbonero R, Mayordomo JI, Tornamira MV, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst. 2001;93(1):31–8. doi: 10.1093/jnci/93.1.31.
  35. Maher DW, Lieschke GJ, Green M, et al. Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial. Ann Intern Med. 1994;121(7):492–501. doi: 10.7326/0003-4819-121-7-199410010-00004.
  36. Mitchell PL, Morland B, Stevens MC, et al. Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients. J Clin Oncol. 1997;15(3):1163–70. doi: 10.1200/JCO.1997.15.3.1163.
  37. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer. 1993;29A(3):319–24. doi: 10.1016/0959-8049(93)90376-q.
  38. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991;325(3):164–70. doi: 10.1056/NEJM199107183250305.
  39. Crawford J, Becker PS, Armitage JO, et al. Myeloid Growth Factors, Version 2.2017. NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(12):1520–41. doi: 10.6004/jnccn.2017.0175.
  40. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8–32. doi: 10.1016/j.ejca.2010.10.013.
  41. Crawford J, Caserta C, Roila F, ESMO Guidelines Working Group. Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications. Ann Oncol. 2010;21(Suppl 5):v248–v251. doi: 10.1093/annonc/mdq195.
  42. Lawrence SM, Corriden R, Nizet V. The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis. Microbiol Mol Biol Rev. 2018;82(1):e00057–17. doi: 10.1128/MMBR.00057-17.
  43. Murphy P. The Neutrophil. Boston: Springer; 1976. pp. 33–67.
  44. Lord BI, Bronchud MH, Owens S, et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo. Proc Natl Acad Sci USA. 1989;86(23):9499–503. doi: 10.1073/pnas.86.23.9499.
  45. Lie AK, Hui CH, Rawling T, et al. Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF. Bone Marrow Transplant. 1998;22(9):853–7. doi: 10.1038/sj.bmt.1701463.
  46. van Der Auwera P, Platzer E, Xu ZX, et al. Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim. Am J Hematol. 2001;66(4):245–51. doi: 10.1002/ajh.1052.
  47. Morstyn G, Campbell L, Souza LM, et al. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988;1(8587):667–72. doi: 10.1016/s0140-6736(88)91475-4.
  48. Shochat E, Rom-Kedar V, Segel LA. G-CSF control of neutrophils dynamics in the blood. Bull Math Biol. 2007;69(7):2299–338. doi: 10.1007/s11538-007-9221-1.
  49. Shochat E, Rom-Kedar V. Novel strategies for granulocyte colony-stimulating factor treatment of severe prolonged neutropenia suggested by mathematical modeling. Clin Cancer Res. 2008;14(20):6354–63. doi: 10.1158/1078-0432.CCR-08-0807.
  50. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9(1):181–218. doi: 10.1146/annurev-pathol-020712-164023.
  51. Hayes MP, Enterline JC, Gerrard TL, Zoon KC. Regulation of interferon production by human monocytes: requirements for priming for lipopolysaccharide-induced production. J Leuk Biol. 1991;50(2):176–81. doi: 10.1002/jlb.50.2.176.
  52. Boneberg EM, Hareng L, Gantner F, et al. Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ. Blood. 2000;95(1):270–6. doi: 10.1182/blood.V95.1.270.
  53. de Kleijn S, Langereis JD, Leentjens J, et al. IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS One. 2013;8(8):e72249. doi: 10.1371/journal.pone.0072249.
  54. Rutella S, Zavala F, Danese S, et al. Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance. J Immunol. 2005;175(11):7085– doi: 10.4049/jimmunol.175.11.7085.
  55. Ali N. Chimeric antigen T cell receptor treatment in hematological malignancies. Blood Res. 2019;54(2):81– doi: 10.5045/br.2019.54.2.81.
  56. Bais S, Bartee E, Rahman MM, et al. Oncolytic virotherapy for hematological malignancies. Adv Virol. 2012;2012:1–8. doi: 10.1155/2012/186512.
  57. Calton CM, Kelly KR, Anwer F, et al. Oncolytic Viruses for Multiple Myeloma Therapy. Cancers (Basel). 2018;10(6):198. doi: 10.3390/cancers10060198.
  58. Matveeva OV, Chumakov PM. Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses. Rev Med Virol. 2018;28(6):e2008. doi: 10.1002/rmv.2008.

Treatment of Aggressive Non-Hodgkin’s Lymphomas in Pregnancy

AUTOIMMUNE THROMBOCYTOPENIA , ,

YaK Mangasarova1, AU Magomedova1, ES Nesterova1, LG Gorenkova1, FE Babaeva1, RG Shmakov2, SK Kravchenko1

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

2 VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina str., Moscow, Russian Federation, 117997

For correspondence: Yana Konstantinovna Mangasarova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(926)395-82-52; e-mail: v.k.jana@mail.ru

For citation: Mangasarova YaK, Magomedova AU, Nesterova ES, et al. Treatment of Aggressive Non-Hodgkin’s Lymphomas in Pregnancy. Clinical oncohematology. 2020;13(3):316–21 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-316-321

ABSTRACT

Background. The management of aggressive lymphomas in pregnancy depends on the time of diagnosis and immunomorphological variant of tumor. The rarity of aggressive lymphomas in pregnant women, the absence of consistent approaches to the treatment of such patients, the lack of data on physical growth of children as well as the incidence of newborns’ congenital and acquired pathology make this subject of vital importance.

Aim. To analyze the treatment results in patients with newly diagnosed aggressive lymphoma at different stages of pregnancy.

Materials & Methods. From 1993 to 2020 at the National Research Center for Hematology 74 pregnant women with lymphomas were treated. Aggressive tumors were detected in 17 (23 %) of them: primary mediastinal (thymic) large B-cell lymphoma (n = 14), anaplastic large-cell lymphoma ALK+ (n = 1), high-grade B-cell lymphoma, unspecified (n = 1), and diffuse large B-cell lymphoma (n = 1). The median age of patients was 30 years (range 21–37 years). The median pregnancy stage on the diagnosis of aggressive lymphoma was 21 weeks (range 11–32 weeks).

Results. In 1 case on the diagnosis of aggressive lymphoma at 11 weeks gestation dexamethasone 8 mg daily was administered up to the second trimester of pregnancy, afterwards the patient received polychemotherapy. On the diagnosis of aggressive lymphoma in the second (n = 13) and third (n = 2) trimesters of pregnancy the patients received polychemotherapy followed by delivery. In the third trimester of pregnancy delivery was performed with subsequent polychemotherapy in 1 patient. There were born 18 babies (1 pregnancy was multifetal): 8 girls and 10 boys.

Conclusion. As a result of the chosen tactics and the work of interdisciplinary team of doctors all patients, who completed the treatment, are followed-up in complete remission. All born babies, despite chemotherapy and perinatal complications, are alive and develop without abnormalities.

Keywords: malignant lymphoproliferative disorders, chemotherapy, primary mediastinal (thymic) large B-cell lymphoma, pregnancy.

Received: April 1, 2020

Accepted: June 22, 2020

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REFERENCES

  1. Lishner M, Avivi I, Apperley JF, et al. Hematologic malignancies in pregnancy: management guidelines from an international consensus meeting. J Clin Oncol. 2016;34(5):501–8. doi: 10.1200/JCO.2015.62.4445.

  2. Ortega J. Multiple agent chemotherapy including bleomycin of non-Hodgkin’s lymphoma during pregnancy. Cancer. 1977;40(6):2829–35. doi: 1002/1097-0142(197712)40:6<2829::aid-cncr2820400613>3.0.co;2-i.

  3. Amit O, Barzilai M, Avivi I. Management of hematologic malignancies: special considerations in pregnant women. Drugs. 2015;75(15):1725–38. doi: 10.1007/s40265-015-0464-0.

  4. Perez CA, Amin J, Aguina LM, et al. Primary mediastinal large B-cell lymphoma during pregnancy. Case Rep Hematol. 2012;2012:1–3. doi: 10.1155/2012/197347.

  5. Lee EJ, Ahn KH, Hong SC, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for diffuse large B-cell lymphoma in pregnancy may be associated with preterm birth. Obstet Gynecol Sci. 2014;57(6):526–9. doi: 10.5468/ogs.2014.57.6.526.

  6. Decker M, Rothermundt C, Hollander G, et al. Rituximab plus CHOP for treatment of diffuse large B-cell lymphoma during second trimester of pregnancy. Lancet Oncol. 2006;7(8):693–4. doi: 1016/s1470-2045(06)70797-5.

  7. Fiascone S, Datkhaeva I, Winer ES, et al. Primary mediastinal large B-cell lymphoma in pregnancy. Leuk Lymphoma. 2016;57(1):240–3. doi: 10.3109/10428194.2015.1049168.

  8. Evens AM, Advani R, Lossos IS, et al. Lymphoma in pregnancy: excellent fetal outcomes and maternal survival in a large multicenter analysis. Blood. 2011;118(21):94. doi: 1182/blood.v118.21.94.94.

  9. Шмаков Р.Г., Ахмедова А.И., Полушкина Е.С. и др. Современные принципы ведения беременности у пациенток с лимфомами. Акушерство и гинекология. 2019;7:40–8. doi: 10.18565/aig.2019.7.40-48.[Shmakov RG, Akhmedova AI, Polushkina ES, et al. Modern principles of pregnancy management in patients with lymphomas. Akusherstvo i ginekologiia. 2019;7:40–8. doi: 10.18565/aig.2019.7.40-48. (In Russ)]

  10. Мангасарова Я.К., Барях Е.А., Воробьев В.И. и др. Первичная медиастинальная В-крупноклеточная лимфома у беременных. Терапевтический архив. 2014;86(7):53–8.[Mangasarova YaK, Baryakh EA, Vorob’ev VI, et al. Primary mediastinal large B-cell lymphoma in pregnancy. Terapevticheskii arkhiv. 2014;86(7):53–8. (In Russ)]

  11. Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poena magna, not anymore. Eur J Cancer. 2006;42(2):126–40. doi: 10.1016/j.ejca.2005.10.014.

  12. Sica A, Vitiello P, Papa A, et al. Use of Rituximab in NHL Malt Type Pregnant in I° Trimester for Two Times. Open Med (Wars). 2019;14:757–60. doi: 10.1515/med-2019-0087.

  13. Cohen-Kerem R, Nulman I, Abramow-Newerly M, et al. Diagnostic radiation in pregnancy: perception versus true risks. J Obstet Gynaecol Can. 2006;28(1):43–8. doi: 10.1016/S1701-2163(16)32039-4.

  14. Kal HB, Struikmans H. Radiotherapy during pregnancy: fact and fiction. Lancet Oncol. 2005;6(5):328–33. doi: 10.1016/S1470-2045(05)70169-8.

  15. Horowitz NA, Benyamini N, Wohlfart K, et al. Reproductive organ involvement in non-Hodgkin lymphoma during pregnancy: a systematic review. Lancet Oncol. 2013;14(7):e275–e282. doi: 10.1016/S1470-2045(12)70589-2.

  16. Testa AC, De Blasis I, Di Legge A, et al. Burkitt’s lymphoma of the breast metastatic to the ovary diagnosed during pregnancy. Ultras Obstet Gynecol. 2013;42(3):364–6. doi: 10.1002/uog.12533.

  17. El-Messidi A, Patenaude V, Abenhaim HA. Incidence and outcomes of women with non-Hodgkin’s lymphoma in pregnancy: A population-based study on 7.9 million births. J Obstet Gynaecol Res. 2015;41(4):582–9. doi: 10.1111/jog.12597.

  18. Framarino-dei-Malatesta M, Sammartino P, Napoli A. Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus? BMC Cancer. 2017;17(1):777. doi: 10.1186/s12885-017-3772-9.

  19. Peterson C, Lester DR Jr, Sanger W. Burkitt’s lymphoma in early pregnancy. J Clin Oncol. 2010;28(9):e136–e138. doi: 10.1200/JCO.2009.24.6355.

  20. Aviles A, Neri N. Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. Clin Lymphoma. 2001;2(3):173–7. doi: 10.3816/clm.2001.n.023.

Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia

ANTINEOPLASTIC THERAPY COMPLICATIONS , , , , , ,

YuN Dubinina1, VO Sarzhevskii2, VYa Melnichenko2

1 Oncology and Hematology Outpatient Clinic, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467

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

For correspondence: Yuliya Nikolaevna Dubinina, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467; Tel.: +7(499)112-25-04; e-mail: medicinemsc@gmail.com

For citation: Dubinina YuN, Sarzhevskii VO, Melnichenko VYa. Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia. Clinical oncohematology. 2019;12(4):461–7 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-461-467

ABSTRACT

The growing number of autologous and allogeneic transplantations of bone marrow and hematopoietic stem cells as well as their technological effectiveness give rise to drug antineoplastic therapies with increased toxicity leading to development of complications. The most serious among this sort of complications are infections. Probability of infections in patients with chemotherapy-induced neutropenia reaches 90 %. In this context the search for an optimal marker of infectious complications becomes more and more important. The present review deals with basic biochemical inflammatory markers and the analysis of trials assessing diagnostic and prognostic value of C-reactive protein, procalcitonin, and presepsin.

Keywords: sepsis, autologous bone marrow transplantation, allogeneic bone marrow transplantation, chemotherapy, infection, procalcitonin, presepsin, C-reactive protein.

Received: May 7, 2019

Accepted: September 11, 2019

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REFERENCES

  1. Passweg JR, Baldomero H, Bade P, et al. Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2018;53(9):1139–48. doi: 10.1038/s41409-018-0153-1.

  2. Ochs L, Shu XO, Miller J, et al. Late infections after allogeneic bone marrow transplantation: comparison of incidence in related and unrelated donor transplant recipients. Blood. 1995;86(10):3979–86.

  3. Sorely JS, Shea TC. Prevention of infections in bone marrow transplant recipients. Infect Dis Clin North Am. 1997;11(2):459–77. doi: 10.1016/s0891-5520(05)70365-2.

  4. Massaro KSR, Costa SF, Leone C, Chamone DAF. Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults. BMC Infect Dis. 2007;7(1). doi: 10.1186/1471-2334-7-137.

  5. Саржевский В.О., Дубинина Ю.Н., Мельниченко В.Я. Диагностическое и прогностическое значение биохимических маркеров инфекционных осложнений высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток при злокачественных лимфопролиферативных заболеваниях. Клиническая онкогематология. 2017;10(1):113–9. doi: 10.21320/2500-2139-2017-10-1-113-119.

    [Sarzhevskii VO, Dubinina YuN, Mel’nichenko VYa. Diagnostic and Prognostic Value of Biochemical Markers of Infectious Complications of High-Dose Therapy with Autologous Hematopoietic Stem Cell Transplantation in Malignant Lymphoproliferative Diseases. Clinical oncohematology. 2017;10(1):113–9. doi: 10.21320/2500-2139-2017-10-1-113-119. (In Russ)]

  6. Zhang W, Zhao Q, Huang H. Febrile neutropenic infection occurred in cancer patients undergoing autologous peripheral blood stem cell transplantation. Transplant Proc. 2015;47(2):523–7. doi: 10.1016/j.transproceed.2015.01.013.

  7. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet. 2002;359(9323):2065–71. doi: 10.1016/s0140-6736(02)08938-9.

  8. Krishnamani K, Gandhi LV, Sadashivudu G, et al. Epedimiologic, clinical profile and factors affecting the outcome in febrile neutropenia. South Asian J Cancer. 2017;6(1):25–7. doi: 10.4103/2278-330X.202565.

  9. Bates DW, Sands K, Miller E, et al. Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group. J Infect Dis. 1997;176(6):1538–51. doi: 10.1086/514153.

  10. Klastersky J, de Naurois J, Rolston K, et al. Management of Febrile Neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(Suppl 5):v111–v118. doi: 10.1093/annonc/mdw325.

  11. Homsi J, Walsh D, Panta R, et al. Infectious complications of advanced cancer. Support Care Cancer. 2000;8(6):487–92.

  12. Zembower TR. Epidemiology of infections in cancer patients. Cancer Treat Res. 2014;161:43–89. doi: 10.1007/978-3-319-04220-6_2.

  13. European Medicines Agency. Guideline on clinical evaluation of diagnostic agents. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003580.pdf. (accessed 30.07.2019).

  14. Павлушкина Л.В., Черневская Е.А., Дмитриева И.Б., Белобородова Н.В. Биомаркеры в клинической практике. Поликлиника. 2013;3:10–4.

    [Pavlushkina LV, Chernevskaya EA, Dmitrieva IB, Beloborodova NV. Biomarkers in clinical practice. Poliklinika. 2013;3:10–4. (In Russ)]

  15. Sbrana A, Torchio M, Comolli G, et al. Use of procalcitonin in clinical oncology: a literature review. New Microbiol. 2016;39(3):174–80.

  16. Pierrakos C, Vincent JV. Sepsis biomarkers: a review. Crit Care. 2010;14(1):R15. doi: 10.1186/cc8872.

  17. Kustan P, Horvath-Szalai Z, Muhl D. Nonconventional Markers of Sepsis. 2017;28(2):122–33.

  18. Colak A, Yilmaz C, Toprak B, Aktogu S. Procalcitonin and Crp as biomarkers in discrimination of community-acquired pneumonia and exacerbation of COPD. J Med Biochem. 2017;36:122–6. doi: 10.1515/jomb-2017-0011.

  19. Gao LQ, Liu XH, Zhang DH, et al. Early diagnosis of bacterial infection in patients with septicopyemia by laboratory analysis of PCT, CRP and IL-6. Exp Ther Med. 2017;13(6):3479–83. doi: 10.3892/etm.2017.4417.

  20. Povoa P, Coelho L, Almeida, et al. Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study. Crit Care. 2006;10(2):R63. doi: 10.1186/cc4892.

  21. Morley JJ, Kushner I. Serum C-reactive protein levels in disease. Ann NY Acad Sci. 1982;389:(1):406–18. doi: 10.1111/j.1749-6632.1982.tb22153.x.

  22. Palmiere C, Augsburger M. Markers for sepsis diagnosis in the forensic setting: state of the art. Croat Med J. 2014;55(2):103–14. doi: 10.3325/cmj.2014.55.103.

  23. Meisner M, Tschaikowsky K, Palmers T. Procalcitonin and CRP in septic shock: Inflammatory parameters with different kinetics. Intens Care Med. 1996;22(S1):s13. doi: 10.1007/BF01921187.

  24. Samraj RS, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock. 2013;40(5):358–65. doi: 10.1097/Shk.0b013e3182a66bd6.

  25. Fujita MQ, Zhu B-L, Ishida K, et al. Serum C-reactive protein levels in postmortem blood – an analysis with special reference to the cause of death and survival time. Forensic Sci Int. 2002;130(2–3):160–6. doi: 10.1016/S0379-0738(02)00381-X.

  26. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805–12. doi: 10.1172/jci18921.

  27. Duzenli KD, Ozdemir ZC, Bor O. Evaluation of febrile neutropenic attacks of pediatric hematology-oncology patients. Turk Pediatr Ars. 2017;52(4):213–20. doi: 10.5152/TurkPediatriArs.2017.5312.

  28. Pineda-Roman M, Barlogie B, Tricot G, et al. High-dose melphalan-based autotransplants for multiple myeloma: the Arkansas experience since 1989 in 3077 patients. Cancer. 2008;112(8):1754–64. doi: 10.1002/cncr.23327.

  29. Kollu V, Mott SL, Khan R, et al. C-Reactive Protein Monitoring Predicts Neutropenic Fever Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma. Cureus. 2018;10(7):e2945. doi: 10.7759/cureus.2945.

  30. Ortega M, Rovira M, Almela M, et al. Measurement of C-reactive protein in adults with febrile neutropenia after hematopoietic cell transplantation. Bone Marrow Transplant. 2004;33(7):741–4. doi: 10.1038/sj.bmt.1704409.

  31. Schots R, Kaufman L, Van Riet I, et al. Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality. Bone Marrow Transplant. 1998;22(1):79–85. doi: 10.1038/sj.bmt.1701286.

  32. Sato M, Nakasone H, Wada H, et al. Prediction of infectious events by the high-sensitivity C-reactive protein level before autologous hematopoietic cell transplantation for lymphoma and multiple myeloma. Transplant Infect Dis. 2013;15(4):E169–E171. doi: 10.1111/tid.12102.

  33. Massaro K, Costa SF. Role of Biomarkers as Predictors of Infection and Death in Neutropenic Febrile Patients after Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis. 2015;7(1):e2015059. doi: 10.4084/MJHID.2015.059.

  34. Sato M, Nakasone H, Oshima K, et al. Prediction of transplant-related complications by C-reactive protein levels before hematopoietic SCT. Bone Marrow Transplant. 2013;48(5):698–702. doi: 10.1038/bmt.2012.193.

  35. Pavlu J, Kew AK, Taylor-Roberts B, et al. Optimizing patient selection for myeloablative allogeneic hematopoietic cell transplantation in chronic myeloid leukemia in chronic phase. Blood. 2010;115(2):4018–20. doi: 10.1182/blood-2010-01-263624.

  36. Wang XS, Shi Q, Shah ND, et al. Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation. Clin Cancer Res. 2014;20(5):1366–74. doi: 10.1158/1078-0432.ccr-13-2442.

  37. Fassas AB, Miceli MH, Grazzlutti M, et al. Serial measurement of serum C-reactive protein levels can identify patients at risk for severe complications following autologous stem cell transplantation. Leuk Lymphoma. 2005;46(8):1159–61. doi: 10.1080/10428190500086121.

  38. Teachey DT, Lacey SF, Shaw PA, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 2016;6(6):664–79. doi: 10.1158/2159-8290.cd-16-0040.

  39. Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res. 2000;49(Suppl 1):S57–61.

  40. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008;36(3):941–52. doi: 10.1097/CCM.0B013E318165BABB.

  41. Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: what is useful? Crit Care Clin. 2006;22(3):503–19. doi: 10.1016/j.ccc.2006.03.003.

  42. Picariello C, Lazzeri C, Valente S, et al. Procalcitonin in acute cardiac patients. Intern Emerg Med. 2011;6(3):245–52. doi: 10.1007/s11739-010-0462-x.

  43. Reinhart K, Bauer M, Riedelmann NC, et al. New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev. 2012;25(4):609–34. doi: 10.1128/cmr.0001612.

  44. Assicot M, Gendrel D, Carsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341(8844):515–8. doi: 10.1016/0140-6736(93)90277-n.

  45. Wu CW, Wu JY, Chen CK, et al. Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis. Support Care Cancer. 2015;23(10):2863–72. doi: 10.1007/s00520-015-2650-8.

  46. Schuttrumpf S, Binder L, Hagemann T, et al. Utility of procalcitonin concentration in the evaluation of patients with malignant diseases and elevated C-reactive protein plasma concentrations. Clin Infect Dis. 2006;43(3):468–73. doi: 10.1086/505394.

  47. Shomali W, Hachem R, Chaftari AM, et al. Can procalcitonin distinguish infectious fever from tumor-related fever in non-neutropenic cancer patients? Cancer. 2012;118(23):5823–9. doi: 10.1002/cncr.27602.

  48. Meidani M, Khorvash F, Abolghasemi H, et al. Procalcitonin and quantitative C-reactive protein role in the early diagnosis of sepsis in patients with febrile neutropenia. South Asian J Cancer. 2013;2(4):216–9. doi: 10.4103/2278-330x.119913.

  49. Ahn S, Lee YS, Lim KS, et al. Adding Procalcitonin to the MASCC risk-index score could improve risk stratification of patients with febrile neutropenia. Support Care Cancer. 2013;21(8):2303–8. doi: 10.1007/s00520-013-1787-6.

  50. Chaftari AM, Hachem R, Reitzel R, et al. Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection. PLoS One. 2015;10(7):e0130999. doi: 10.1371/journal.pone.0130999.

  51. Jimeno A, Garcia-Velasco A, Val del O, et al. Assessment of Procalcitonin as a Diagnostic and Prognostic Marker in Patients with Solid Tumors and Febrile Neutropenia. Cancer. 2004;100(11):2462–9. doi: 10.1002/cncr.20275.

  52. Carnino L, Betteto S, Loiacono M, et al. Procalcitonin as a predictive marker of infections in chemoinduced neutropenia. J Cancer Res Clin Oncol. 2010;136(4):611–5. doi: 10.1007/s00432-009-0699-9.

  53. Diness LV, Maraldo MV, Mortensen CE, et al. Procalcitonin and C-reactive protein as markers of bacterial infection in patients with solid tumors. Dan Med J. 2014;61(12):A4984.

  54. Giamarellou H, Giamarellos-Bourboulis EJ, Repoussis P, et al. Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study. Clin Microbiol Infect. 2004;10(7):628–33. doi: 10.1111/j.1469-0691.2004.00883.x.

  55. Persson L, Engervall P, Magnuson A, et al. Use of inflammatory markers for early detection of bacteraemia in patients with febrile neutropenia. Scand J Infect Dis. 2004;36(5):365–71. doi: 10.1080/00365540410020217.

  56. Ruokonen E, Nousiainen T, Pulkki K, et al. Procalcitonin concentrations in patients with neutropenic fever. Eur J Clin Microbiol Infect Dis. 1999;18(4):283–5. doi: 10.1007/s100960050277.

  57. Robinson JO, Lamoth F, Bally F, et al. Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever? PLoS One. 2011;6(4):e18886. doi: 10.1371/journal.pone.0018886.

  58. Patout M, Salaun M, Brunel V, et al. Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers. Clin Biochem. 2014;47(18):263–7. doi: 10.1016/j.clinbiochem.2014.09.002.

  59. Scheinpflug K, Schalk E, Grabert E, et al. Procalcitonin is not useful to discriminate between infectious and noninfectious CrP elevations in patients with non-small cell lung cancer. Infect Control Hosp Epidemiol. 2015;36(9):1117–8. doi: 10.1017/ice.2015.134.

  60. Yaegashi Y, Sato N, Suzuki Y, et al. Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. J Infect Chemother. 2005;11(5):234–8. doi: 10.1007/s10156-005-0400-4.

  61. Shirakawa K, Naitou K, Hirose J, et al. The new sepsis marker, sCD14-ST, induction mechanism in the rabbit sepsis models. Crit Care. 2010;14(Suppl 2):P19. doi: 10.1186/cc9122.

  62. Shozushima T, Takahashi G, Matsumoto N, et al. Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome. J Infect Chemother. 2011;17(6):764–9. doi: 10.1007/s10156-011-0254-x.

  63. Endo S, Suzuki Y, Takahashi G, et al. Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study. J Infect Chemother. 2012;18(6):891–7. doi: 10.1007/s10156-012-0435-2.

  64. Urbonas V, Eidukaite A, Tamuliene I. The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia. Cytokine. 2013;62(1):34–7. doi: 10.1016/j.cyto.2013.02.030.

  65. Olad E, Sedighi I, Mehrvar A, et al. Presepsin (scd14) as a marker of serious bacterial infections in chemotherapy induced severe neutropenia. Iran J Pediatr. 2014;24(6):715–22.

  66. Korpelainen S, Intke C, Hamalainen S, et al. Soluble CD14 as a Diagnostic and Prognostic Biomarker in Hematological Patients with Febrile Neutropenia. Dis Mark. 2017;2017:1–8. doi: 10.1155/2017/9805609.

  67. Koh H, Aimoto M, Katayama T, et al. Diagnostic value of levels of presepsin (soluble CD14-subtype) in febrile neutropenia in patients with hematological disorders. J Infect Chemother. 2016;22(7):466–71. doi: 10.1016/j.jiac.2016.04.002.

  68. Stoma I, Karpov I, Uss A, et al. Diagnostic value of sepsis biomarkers in hematopoietic stem cell transplant recipients in a condition of high prevalence of gram-negative pathogens. Hematol Oncol Stem Cell Ther. 2017;10(1):15–21. doi: 10.1016/j.hemonc.2016.09.002.

  69. Ebisawa K, Koya J, Nakazaki K, et al. Usefulness of presepsin for early detection of infections in patients with hematologic disorders. Clin Chim Acta. 2018;486:374–80. doi: 10.1016/j.cca.2018.08.032.

The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

LYMPHOID TUMORS , , ,

KD Kaplanov1,2,3, TYu Klitochenko1,3, AL Shipaeva1, MN Shirokova1, IV Matveeva1, NB Lavrishina1

1 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Research Center, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

3 Volgograd State Medical University, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

For correspondence: Kamil’ Daniyalovich Kaplanov, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Klitochenko TYu, Shipaeva АL, et al. The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity. Clinical oncohematology. 2017;10(3):358–65 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-358-365

ABSTRACT

Background. Among the newly diagnosed patients with Hodgkin’s lymphoma (HL), the proportion of elderly patients account for 15–35 %. In > 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In ≥ 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively.

Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”.

Materials & Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged ≥ 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04).

Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004).

Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

Keywords: Hodgkin’s lymphoma, elderly patients, comorbidity, chemotherapy.

Received: December 22, 2016

Accepted: March 5, 2017

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REFERENCES

  1. Landgren O, Algernon C, Axdorph U, et al. Hodgkin’s lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis. Haematologica. 2003;88(4):438–44.
  2. Engert A, Ballova V, Haverkamp H, et al. Hodgkin’s lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin’s Study Group. J Clin Oncol. 2005;23(22):5052–60. doi: 10.1200/jco.2005.11.080.
  3. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012;119(3):692–5. doi: 10.1182/blood-2011-09-378414.
  4. Stark GL, Wood KM, Jack F, et al. Hodgkin’s disease in the elderly: a population-based study. Br J Haematol. 2002;119(2):432–40. doi: 10.1046/j.1365-2141.2002.03815.x.
  5. Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506–14.
  6. Evens AM, Hong F, Gordon LI, et al. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013;161(1):76–86. doi: 10.1111/bjh.12222.
  7. Ballova V, Ruffer JU, Haverkamp H, et al. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin’s disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005;16(1):124–31. doi: 10.1093/annonc/mdi023.
  8. Halbsguth TV, Nogova L, Mueller H, et al. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide,vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2010;116(12):2026–32. doi: 10.1182/blood-2009-11-253211.
  9. Levis A, Anselmo AP, Ambrosetti A, et al. VEPEMB in elderly Hodgkin’s lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004;15(1):123–8. doi: 10.1093/annonc/mdh012.
  10. Proctor SJ, Wilkinson J, Jones G, et al. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012;119(25):6005–15. doi: 10.1182/blood-2011-12-396556.
  11. Boll B, Bredenfeld H, Gorgen H, et al. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011;118(24):6292–8. doi: 10.1182/blood-2011-07-368167.
  12. Boll B, Gorgen H, Fuchs M, et al. ABVD in older early stage Hodgkin lymphoma patients treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 Trials. J Clin Oncol. 2013;31(12):1522–9. doi: 10.1200/jco.2012.45.4181.
  13. Weekes CD, Vose JM, Lynch JC, et al. Hodgkin’s disease in the elderly: improved treatment outcome with a doxorubicin-containing regimen. J Clin Oncol. 2002;20(4):1087–93. doi: 10.1200/jco.20.4.1087.
  14. Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385(9976):1418. doi: 10.1016/s0140-6736(14)61469-0.
  15. Леонтьева А.А., Демина Е.А. Лечение распространенных стадий лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266.
    [Leont’eva AA, Demina EA. Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review. Clinical oncohematology. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266. (In Russ)]
  16. Borchmann P, Eichenauer DA, Pluetschow A, et al. Targeted BEACOPP variants in patients with newly diagnosed advanced stage classical Hodgkin lymphoma: Final analysis of a randomized phase II study. Blood. 2015;126:580 (abstract).
  17. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 29–30.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders). Moscow: Buki Vedi Publ.; 2016. pp. 29–30. (In Russ)]
  18. Forero-Torres A, Holkova B, Goldschmidt J, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015;126(26):2798–804. doi: 10.1182/blood-2015-06-644336.
  19. Enblad G, Gustavsson A, Sundstrom C, Glimelius B. Patients above sixty years of age with Hodgkin’s lymphoma treated with a new strategy. Acta Oncol. 2002;41(7):659–67. doi: 10.1080/028418602321028283.
  20. Kim HK, Silver B, Li S, et al. Hodgkin’s disease in elderly patients (≥60): Clinical outcome and treatment strategies. Int J Radiat Oncol Biol Phys. 2003;56(2):556–60. doi: 10.1016/s0360-3016(02)04596-0.
  21. Van Spronsen DJ, Janssen-Heijnen MLG, Lemmens VEPP, et al. Independent prognostic effect of co-morbidity in lymphoma patients: results of the population-based Eindhoven Cancer Registry. Eur J Cancer. 2005;41(7):1051–7. doi: 10.1016/j.ejca.2005.01.010.
  22. Macpherson N, Klasa RJ, Gascoyne R, et al. Treatment of elderly Hodgkin’s lymphoma patients with a novel 5-drug regimen (ODBEP): a phase II study. Leuk Lymphoma. 2002;43(7):1395–402. doi: 10.1080/10428190290033332.
  23. Kolstad A, Nome O, Delabie J, et al. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin’s lymphoma. Leuk Lymphoma 2007;48(3):570–6. doi: 10.1080/10428190601126610.
  24. Klimm B, Eich HT, Haverkamp H, et al. Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin’s lymphoma: an analysis from the German Hodgkin Study Group. Ann Oncol. 2007;18(2):357–63. doi: 10.1093/annonc/mdl379.

WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review)

REVIEWS , , ,

NN Mamaev, YaV Gudozhnikova, AV Gorbunova

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +(7)911-760-50-86; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gudozhnikova YaV, Gorbunova AV. WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2016;9(3):257-64 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-257-264

ABSTRACT

The article discusses recent data on the WT1 gene overexpression phenomenon in patients with acute leukemias, myelodysplastic syndromes, chronic myeloid leukemia, non-Hodgkin’s lymphomas, and multiple myeloma. It demonstrates that monitoring of the WT1 gene overexpression proves to be effective during the posttransplantation period, as well as after the induction chemotherapy. This approach may be applied in diagnosing the minimal residual disease and early detection of leukemia relapses, as well as their timely and controlled treatment. There are other promising fields of research, such as testing autografts for the presence or absence of tumor elements, as well as evaluation of the efficacy of induction chemotherapy in high risk patients.

Keywords: WT1 gene overexpression phenomenon, hematopoietic stem cell transplantation, chemotherapy, molecular treatment monitoring.

Received: February 8, 2016

Accepted: March 30, 2016

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REFERENCES

  1. Call KM, Glaser T, Ito CI, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor gene locus. Cell. 1990;60(3):509–20. doi: 10.1016/0092-8674(90)90601-a.
  2. Rose EA, Glaser T, Jones C, et al. Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms’ tumor gene. Cell. 1990;60(3):495–508. doi: 10.1016/0092-8674(90)90600-j.
  3. Miwa H, Beran M, Saunders GF. Expression of the Wilms’ tumor gene (WT1) in human leukemias. Leukemia. 1992;6(5):405–9.
  4. Inoue K, Ogawa H, Sonoda Y, et al. Aberrant overexpression of the Wilms’ tumour gene (WT1) in human leukemia. Blood. 1997;88(4):1405–12.
  5. Абдулкадыров К.М., Грицаев С.В., Капустин С.И. и др. Экспрессия гена опухоли Вилмса (WT1) в клетках крови больных миелодиспластическим синдромом. Вопросы онкологии. 2004;50(6):668–71.
    [Abdulkadyrov KM, Gritsaev SV, Kapustin SI, et al. Wilms’ tumor gene (WT1) expression in blood cells of patients with myelodysplastic syndrome. Voprosy oncologii. 2004;50(6):668–71. (In Russ)]
  6. Yang L, Han Y, Suarez Saiz F, et al. A tumor suppressor and oncogene: The WT1 story. Leukemia. 2007;21(5):868–76. doi: 1038/sj.leu.2404624.
  7. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Аллогенная трансплантация гемопоэтических стволовых клеток при миелодиспластических синдромах и клиническое значение гиперэкспрессии гена WT1. Клиническая онкогематология. 2014;7(4):551–63.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and clinical significance of WT1 gene overexpression. Klinicheskaya onkogematologiya. 2014;7(4):551–63. (In Russ)]
  8. Мамаев Н.Н., Горбунова А.В., Бархатов И.М. и др. Молекулярный мониторинг течения острых миелоидных лейкозов по уровню экспрессии гена WT1 после аллогенной трансплантации гемопоэтических столовых клеток. Клиническая онкогематология. 2015;8(3):309–20. doi: 10.21320/2500-2139-2015-8-3-309-320.
    [Mamaev NN, Gorbunova AV, Barkhatov IM, et al. Molecular monitoring of WT1 gene expression level in acute myeloid leukemias after allogeneic hematopoietic stem cell transplantation. Clinical oncohematology. 2015;8(3):309–20. doi: 10.21320/2500-2139-2015-8-3-309-320. (In Russ)]
  9. Israyelyan A, Goldstein L, Tsai W, et al. Real-time assessment of relapse risk based on the WT1 marker in acute leukemia and myelodysplastic syndrome patients after hematopoietic cell transplantation. Bone Marrow Transplant. 2015;50(1):26–33. doi: 10.1038/bmt.2014.209.
  10. Iwasaki T, Sugisaki Ch, Nagata K, et al. Wilms’ tumor 1 message and protein expression in bone marrow failure syndrome and acute leukemia. Pathol Int. 2007;57(10):645–51. doi: 10.1111/j.1440-2007.02153.x.
  11. Tatsumi N, Hojo N, Yamada O, et al. Deficiency in WT1-targeting microRNA-125a leads to myeloid malignancies and urogenital abnormalities. Oncogene. 2015;35(8):1003–14. doi: 10.1038/onc.2015.154.
  12. Inoue K, Sugiyama H, Ogawa H, et al. WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood. 1994;84(9):3071–9.
  13. Drakos E, Rassidakis GZ, Tsioli F, et al. Differential expression of WT1 gene product in non-Hodgkin lymphomas. Appl Immunohistochem. Mol Morphol. 2005;13(2):132–7. doi: 10.1097/01.pai.0000143786.62974.66.
  14. Hatta Y, Takeuchi J, Saitoh T, et al. WT1 expression level and clinical factors in multiple myeloma. J Exp Clin Cancer Res. 2005;24(4):595–9.
  15. Na I-K, Kreuzer K-A, Lupberger J, et al. Quantitative RT-PCR of Wilms tumor gene transcripts(WT1) for the molecular monitoring of patients with accelerated phase bcr/abl + CML. Leuk Res. 2005;29(3):343–5. doi: 10.1016/j.leukres.2004.08.003.
  16. Chiusa L, Francia di Celle P, Campisi P, et al. Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute lymphoblastic leukemia. Haematologica. 2006;91(2):270–1. doi: 10.0000/www.haematologica.org/content/91/2/270.short.
  17. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103(8):2794–7. doi: 10.1073/pnas.0510423103.
  18. Cao X, Gu WY, Chen ZX, et al. Bone marrow WT1 gene expression and clinical significance in chronic myelogenous leukemia. Zhonghua Nei Ke Za Zhi. 2007;46(4):277–9.
  19. Otahalova E, Ullmannova-Benson V, Klamova FI, et al. WT1 expression in peripheral leukocytes of patients with chronic myeloid leukemia serves for the prediction of imatinib resistance. Neoplasma. 2009;56(5):393–7. doi: 10.4149/neo_2009_05_393.
  20. Heesch S, Goekbuget N, Stroux A, et al. Prognostic implications and expression of the Wilms tumor 1 (WT1) gene in adult T-lymphoblastic leukemia. 2010;95(6):942–9. doi: 10.3324/haematol.2009.016386.
  21. Аксенова Е.В. Стандартизированное исследование экспрессии генов BCR-ABL, PRAME и WT1 у больных хроническим миелолейкозом: Диc. ¼ канд. мед. наук. М., 2011. 138 с.
    [Aksyenova EV. Standartizirovannoe issledovanie expressii genov BCR-ABL, PRAME I WT1 u bolnykh chronicheskim myeloleukosom. (Standardized evaluation of the BCR-ABL, PRAME and WT1 gene expression in patients with chronic myeloid leukemia.) [dissertation] Moscow; 2011. 138 p. (In Russ)]
  22. Гапонова Т.В. Экспрессия опухолеассоциированных генов PRAME, WT1 и XIAP у больных множественной миеломой в процессе интенсивной терапии и аутотрансплантации: Диc. ¼ канд. мед. наук. М., 2011. 141 с.
    [Gaponova TV. Expressia opucholeassocirovannykh genov PRAME, WT1 i XIAP u bolnykh mnozhestvennoi myelomoi v processe intensivnoi therapii I autotransplantacii. (Tumor-associated PRAME, WT1 and XIAP gene expression in patients with multiple myeloma during intensive therapy and autografting.) [dissertation] Moscow; 2011. 141 p. (In Russ)]
  23. Tyler EM, Jungbluth AA, O’Reilly RJ, Koehne G. WT1-specific responses in high-risk multiple myeloma patients undergoing allogeneic T-cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions. 2012;121(2):308–17. doi: 10.1182/blood-2012-06-435040.
  24. Ujj Z, Buglyo G, Udvardy M, et al. WT1 overexpression affecting clinical outcome in non-Hodgkin lymphomas and adult acute lymphoblastic leukemia. Pathol Oncol Res. 2013;20(3):565–70. doi: 10.1007/s12253-013-9729-
  25. Inoue K, Ogawa H, Yamagami T, et al. Long–term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels. Blood. 1996;88(6):2267–78.
  26. Kletzel N, Olzewski M, Huang W, et al. Utility of WT1 as a reliable tool for the detection of minimal disease in children with leukemia. Pediatr Dev Pathol. 2002;5(3):269–75. doi: 10.1007/s10024-001-0208-x.
  27. Cilloni D, Gottardi E, De Micheli D, et al. Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring residual disease in acute leukemia patients. 2002;16(10):2115–21. doi: 10.1038/sj.leu.2402675.
  28. Cilloni D, Giuseppe S, Gottardi E, et al. WT1 as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Hematol. 2004;112(1–2):79–84. doi: 10.1159/000077562.
  29. Cilloni D, Renneville A, Hermitte F, et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: A European LeukemiaNet study. J Clin Oncol. 2009;27(31):5195–201. doi: 10.1200/jco.2009.22.4865.
  30. Weisser M, Kern W, Rauhut S, et al. Prognostic impact of RTPCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. 2005;19(8):1416–23. doi: 10.1038/sj.leu.2403809.
  31. Candoni A, Toffoletti E, Gallina R, et al. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant. 2011;25(2):308–16. doi: 10.1111/j.1399-0012.2010.01251.x.
  32. Gray JX, McMillen L, Mollee P, et al. WT1 expression as a marker of minimal residual disease predicts outcome in acute myeloid leukemia when measured post-transplantation. Leuk Res. 2012;36(4):453–8. doi: 10.1016/j.leukres.2011.09.005.
  33. Kwon M, Martinez-Laperche C, Infante M, et al. Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ Tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell trans-plantation: Correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant. 2012;18(8):1235–42. doi: 10.1016/j.bbmt.2012.01.012.
  34. Polak J, Hajkova H, Haskovec C, et al. Quantitative monitoring of WT1 expression in peripheral blood before and after allogeneic stem cell transplantation for acute myeloid leukemia – a useful tool for early detection of minimal residual disease. 2013;60(1):74–82. doi: 10.4149/neo_2013_011.
  35. Cilloni D, Messa F, Arruga F, et al. Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1 transcript levels in peripheral blood samples collected after chemotherapy. Haematologica. 2008;93(6):921–4. doi: 10.3324/haematol.12165.
  36. Andersson C, Li X, Lorenz F, et al. Reduction in WT1 gene expression during early treatment predicts the outcome in patients with acute myeloid leukemia. Diagn Mol Pathol. 2012;21(4):225–33. doi: 10.1097/pdm.0b013e318257ddb9.
  37. Mossallam GI, Hamid TM, Mahmoud HK, et al. Prognostic significance of WT1 expression at diagnosis and end of induction in Egyptian adult acute myeloid leukemia patients. Hematology. 2013;18(2):69–73. doi: 10.1179/1607845412Y.0000000048.
  38. Ujj Z, Buglyo G, Udvardy M, et al. WT1 expression in adult acute myeloid leukemia: Assessing its presence, magnitude and temporal changes as prognostic factors. Pathol Oncol Res. 2015;22(1):217–21. doi: 10.1007/s12253-015-0002-
  39. Rein LAM, Chao NJ. WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy. Expert Opin Invest Drugs. 2014;23(3):417–26. doi: 10.1517/13543784.2014.889114.
  40. Paschka P, Marcucci G, Ruppert A.S, et al. Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol. 2008;26(28):4595–602. doi: 10.1200/jco.2007.15.2058.
  41. Sugiyama H. WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol. 2010;40(5):377–87. doi: 10.1093/jjco/hyp194.
  42. Vidovic K, Svensson T, Nilsson B, et al. Wilms’ tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells. Leukemia. 2010;24(5):9982–1000. doi: 10.1038/leu.2010.33.
  43. Essafi A, Webb A, Berry RL, et al. A WT1-controlled chromatin switching mechanism underpins tissue-specific wnt4 activation and repression. Dev Cell. 2011;21(3):559–74. doi: 10.1016/j.devcel.2011.07.014.
  44. Huff V. Wilms’ tumours: about tumour suppressor genes, an oncogene and chameleon gene. Nat Rev Cancer. 2001;11(2):111–21. doi: 10.1038/nrc3002.
  45. Morrison AA, Viney RL, Landomery MR. The post-transcriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta. 2008;1785(1):55–62. doi: 10.1016/j.bbcan.2007.10.002.
  46. Owen C, Fitzgibbon J, Paschka P. The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukemias. Hematol Onc 2010;28(1):13–9. doi: 10.1002/hon.931.
  47. Haber DA, Sohn RL, Buckler AJ, et al. Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci USA. 1991;88(21):9618–22. doi: 10.1073/pnas.88.21.9618.
  48. Keilholz U, Menssen HD, Gaiger A, et al. Wilms’ tumor gene 1(WT1) in human neoplasia. 2005;19(8):1318–23. doi: 10.1038/sj.leu.2403817.
  49. Hosen N, Shirakata T, Nishida S, et al. The Wilms’ tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis. Leukemia. 2007;21(8):1783–91. doi: 10.1038/sj.leu.2404752.
  50. Miller-Hodges E, Hohenstein P. WT1 in disease: shifting the epithelial-mesenchymal balance. J Pathol. 2012;226(2):229–40. doi: 10.1002/path.2977.
  51. Cunningham TJ, Palumbo I, Grosso M, et al. WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio. Blood. 2013;122(2):188–92. doi: 10.1182/blood-2012-11-466086.
  52. Patmasirivat P, Fraizer G, Kantarjian H, Saunders GF. WT1 and GATA1 expression in myelodysplastic syndrome and acute leukemia. Leukemia. 1999;13(6):891–900. doi: 10.1038/sj.leu.2401414.
  53. Gaiger A, Linnerth B, Mann G, et al. Wilms’ tumour gene (wt1) expression at diagnosis has no prognostic relevance in childhood acute lymphoblastic leukemia treated by an intensive chemotherapy protocol. Eur J Haematol. 2009;63(2):86–93. doi: 10.1111/j.1600-0609.1999.tb01121.x.
  54. Arlyaratana S, Loeb DM. The role of the Wilms tumour gene (WT1) in normal and malignant hematopoiesis. Expert Rev Mol Med. 2007;9(14):1–17. doi: 10.1017/s1462399407000336.
  55. Ellisen LW, Carlesso N, Cheng T, et al. The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J. 2001;20(8):1897–909. doi: 10.1093/emboj/20.8.1897.
  56. Scharnhorst V, van den Eb AJ, Jochemsen AG. WT1 proteins: functions in growth and differentiation. Gene. 2001;273(2):141–61. doi: 10.1016/s0378-1119(01)00593-5.
  57. Baird PN, Simmons PJ. Expression of the Wllms’ tumor gene (WT1) in normal hematopoiesis. Eur Haematol. 1997;25(4):312–20.
  58. Lange T, Hubmann M, Burkhard R, et al. Monitoring of WT1 expression in PB and CD34+ donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. 2011;25(3):498–505. doi: 10.1038/leu.2010.283.
  59. Schmid D, Heinze G, Linnert B, et al. Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia. Leukemia. 1997;11(5):639–43. doi: 10.1038/sj.leu.2400620.
  60. Lyu X, Xin Y, Mi R, et al. Overexpression of Wilms’ Tumor 1 gene as a negative prognostic indicator in acute myeloid leukemia. PLoS One. 2014;9(3):e92470. doi: 10.1371/journal.pone.0092470.
  61. Wochlecke C, Wittig S, Arndt C, Gruhn B. Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases. J Cancer Res Clin. Oncol. 2014;141(3):523–9. doi: 10.1007/s00432-014-1832-y.
  62. Zhao X-S, Jin S, Zhu H-H, et al. Wilms’ tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011;47(4):499–507. doi: 10.1038/bmt.2011.121.
  63. Nomdedeu JF, Hoyos M, Carricondo M, et al. Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML. Leukemia. 2013;27(11):2157–64. doi: 10.1038/leu.2013.111.
  64. Alonso-Domingues JM, Tenorio M, Velasco D, et al. Correlation of WT1 expression with the burden of total and residual leukemic blasts in bone marrow samples of acute myeloid leukemia patients. Cancer Genet. 2012;205(4):190–1. doi: 10.1016/j.cancergen.2012.02.008.
  65. Tamaki H, Ogawa H, Inoue K, et al. Increased expression of the Wilms tumor gene (WT1) at relapse in acute leukemia. Blood. 1996;88(11):4396–8.
  66. Frairia C, Aydin S, Riera L, et al. WT1 expression in аcute myeloid leukaemia: a useful marker for improving therapy response evaluation. 2013;122(21):2588 (abstract).
  67. Willasch AM, Gruhn B, Coliva T, et al. Standartization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study. 2009;23(8):1472–9. doi: 10.1038/leu.2009.51.
  68. Lapillonne H, Renneville A, Auvrignon A, et al. High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia. J Clin Oncol. 2006;24(10):1507–15. doi: 10.1200/jco.2005.03.5303.
  69. Liu J, Wang Yu, Xu L-P, et al. Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia-rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(7):929–36. doi: 10.1016/j.bbmt.2014.03.008.
  70. Ogawa H, Tamaki H, Ikegame K, et al. The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia. Blood. 2003;101(5):1698–704. doi: 10.1182/blood-2002-06-
  71. Yoon JH, Kim HJ, Shin SH, et al. BAALC and WT1 expression from diagnosis to hematopoietic stem cell transplantation: consecutive monitoring in adult patients with core-binding-factor-positive AML. Eur J Haematol. 2013;91(2):112–21. doi: 10.1111/ejh.12142.
  72. Yoon JH, Kim H-J, Kim J-W, et al. Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation. Bone Marrow Transplant. 2014;49(12):1466–74. doi: 10.1038/bmt.2014.180.
  73. Miyagi T, Ahuja H, Kudota T, et al. Expression of the candidate Wilms’ tumor gene, WT1, in human leukemia cells. Leukemia. 1993;7(7):970–7.
  74. Miyawaki S, Hatsumi N, Tamaki T, et al. Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia. Leuk Lymphoma. 2010;51(10):1855–61. doi: 10.3109/10428194.2010.507829.
  75. Little M, Wells C. A clinical overview of WT1 gene mutations. Hum Mutat. 1997;9(3):209–25. doi: 10.1002/(sici)1098-1004(1997)9:3<209::aid-humu2>3.0.co;2-2.
  76. Mori N, Okada M, Motoji T, et al. Mutation of the WT1 gene in myelodysplastic syndrome and acute myeloid leukemia post myelodysplastic syndrome. Br J Haematol. 1999;105(3):844–5. doi: 10.1046/j.1365-1999.01497.x.
  77. Damm F, Heuser M, Morgan M, et al. Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a favorable outcome in patients with cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2010;28(4):578–85. doi: 10.1200/jco.2009.23.0342.
  78. Hou HA, Huang TC, Lin LI, et al. WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system. Blood. 2010;115(25):5222–31. doi: 10.1016/s1040-1741(10)79528-
  79. Shen Y, Zhu Y-M, Fan X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood. 2011;118(20):5593–603. doi: 10.1182/blood-2011-03-
  80. Luo S, Yu K, Yan QX, et al. Analysis of WT1 mutations, expression levels and single nucleotide polymorphism rs16754 in de novo non-M3 acute myeloid leukemia. Leuk Lymphoma. 2014;56(2):349–57. doi: 10.3109/10428194.2013.791985.
  81. Park SH, Lee HJ, Kim I-S, et al. Incidences and prognostic impact of c-KIT, WT1, CEBPA, and CBL mutations, and mutations associated with epigenetic modification in core binding factor acute myeloid leukemia: a multicenter study in Korean population. Ann Lab Med. 2015;35(3):288–97. doi: 10.3343/alm.2015.35.3.288.
  82. Rampal R, Alkalin A, Madzo J, et al. DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep. 2014;9(5):1841–55. doi: 10.1016/j.celrep.2014.11.004.
  83. Zhang Q, Zhang Q, Li Q. Monitoring of WT1 and its target gene IRF8 expression in acute myeloid leukemia and their significance. Int J Lab Hematol. 2015;37(4):e67–71. doi: 10.1111/ijlh.12309.
  84. Brieger J, Weidmann E, Fenchel K, et al. The expression of the Wilms’ tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells. Leukemia. 1994;8(12):2138.
  85. Brieger J, Weidmann E, Maurer U, et al. The Wilms’ tumor gene is frequently expressed in acute myeloblastic leukemia and may provide a marker for residual blast cells detectable by PCR. Ann Oncol. 1995;6(8):811–66.
  86. Bergmann L, Miething C, Maurer U, et al. High levels of Wilms’ tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood. 1997;90(3):1217–25.
  87. Ogawa H, Ikegame K, Kawakami M, Tamaki H. WT1 gene transcript assay for relapse in acute leukemia after transplantation. Leuk Lymphoma. 2004;45(9):1747–53. doi: 10.1080/10428190410001687503.
  88. Rodrigues PC, Oliveira SN, Vaina MB, et al. Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2007;49(2):133–8. doi: 10.1002/pbc.20953.
  89. Miglino M, Colombo N, Pica C, et al. Wt1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia. Leuk Lymphoma. 2011;52(10):1961–9. doi: 10.3109/10428194.2011.585673.
  90. Zhao BR, Tang XW, Cen JN, et al. Correlation between clinical outcome and WT1 detection after hematopoietic stem cell transplantation in acute leukemia. Zhonghua Yi Xue Za Zhi. 2011;91(20):1375–8.
  91. Gaiger A, Schmid D, Heinze G, et al. Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia. Leukemia. 1998;12(12):1886–94. doi: 10.1038/sj.leu.2401213.
  92. Barragan E, Cervera J, Bolufer P, et al. Prognostic implications of Wilms’ tumor gene (WT1) expression in patients with de novo acute myeloid leukemia. Haematologica. 2004;89(8):926–33.
  93. Yi-ning Y, Xiao-rui W, Chu-xian Z, et al. Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta-analyse. Ann Hematol. 2015;94(6):929–38. doi: 10.1007/s00277-014-2295-
  94. Nowakowska-Kopera A, Sacha T, Florek I, et al. Wilms’ tumor gene 1 expression analysis by real-time quantitative polymerase chain reaction for monitoring of minimal residual disease in acute leukemia. Leuk Lymphoma. 2009;50(8):1326–32. doi: 10.1080/10428190903050021.
  95. Guillaumet-Adkins A, Richter J, Odera MD, et al. Hypermethylation of the alternative AWT1 promotor in hematological malignancies is a highly specific marker for acute myeloid leukemias despite high expression levels. J Hematol Oncol. 2014;7(1):4. doi: 10.1186/1756-8722-7-4.
  96. Capelli D, Attolico I, Saraceli F, et al Early cumulative incidence of relapse in 80 acute myeloid leukemia patients after chemotherapy and transplant post-consolidation treatment: prognostic role of post-induction WT1. 40th EBMT Meeting; 2014 30 March – 2 April; Milan, Italy; 2014: Abstract P287.
  97. Messina C, Candoni A, Carraba MG, et al. Wilms’ tumor gene 1 transcript levels in leukopheresis on peripheral blood hematopoietic cells predict relapse risk in patients autografted for acute myeloid leukemia. Biol Blood Marrow Transpl. 2014;20(10):1586–91. doi: 10.1016/j.bbmt.2014.06.017.
  98. Messina C, Sala E, Carrabba M, et al. Early post-allogeneic transplantation WT1 transcript positivity predicts AML relapse. 40th EBMT Meeting; 2014 30 March – 2 April; Milan, Italy; 2014: Abstract P239.
  99. Gianfaldoni G, Mannelli F, Ponziani V, et al. Early reduction of WT1 transcripts during induction chemotherapy predicts for longer disease free and overall survival in acute myeloid leukemia. Haematologica. 2010;95(5):833–6. doi: 10.3324/haematol.2009.011908.
  100. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Трансплантация гемопоэтических стволовых клеток при остром миелоидном лейкозе с транслокацией t(8;21)(q22;q22). Клиническая онкогематология. 2013;6(4):439–44.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Hemopoietic stem cell transplantation in AML patients with t(8;21)(q22;q22) translocation. Klinicheskaya onkogematologiya. 2013;6(4):439–44. (In Russ)]
  101. 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 post-transplantation 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 onkogematologiya. 2014;7(1):71–5. (In Russ)]
  102. Barragan E, Pajuelo JC, Ballester S, et al. Minimal residual disease detection in acute myeloid leukemia by mutant nucleophosmin (NPM1): comparison with WT1 gene expression. Clin Chim Acta. 2008;395(1–2):120–3. doi: 10.1016/j.cca.2008.05.021.
  103. Ostergaard M, Olesen LH, Hasle H, et al. WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukemia patients – results from a single-centre study. Br J Haematol. 2004;125(5):590–600. doi: 10.1111/j.1365-2004.04952.x.
  104. Zhao XS, Yan CH, Liu DH, et al. Combined use of WT1 and flow cytometry monitoring can promote sensitivity of predicting relapse after allogeneic HSCT without affecting specificity. Ann Hematol. 2013;92(8):1111–9. doi: 10.1007/s00277-013-1733-
  105. Candoni A, Tiribelli M, Toffoletti E, et al. Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia. Eur J Haematol. 2009;82(1):61–8. doi: 10.1111/j.1600-2008.01158.x.
  106. Ommen HB, Nyvold CG, Braendstrup K, et al. Relapse prediction in acute myeloid leukemia patients in complete remission using WT1 as a molecular marker: development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals. Br J Haematol. 2008;141(6):782–991. doi: 10.1111/j.1365-2008.07132.x.
  107. Yamauchi T, Negoro E, Lee S, et al. Detectable Wilms’ tumor-1 transcription at treatment completion is associated with poor prognosis of acute myeloid leukemia: a single institution’s experience. Anticancer Res. 2013;33(8):3335–40.
  108. Woehlecke C, Wittig S, Sanft J, et al. Detection of relapse after hematopoietic stem cell transplantation in childhood by monitoring of WT1 expression and chimerism. J Cancer Res Clin Oncol. 2015;141(7):1283–90. doi: 10.1007/s00432-015-1919-
  109. Jin S, Liu DH, Xu LP, et al. The significance of dynamic detection of WT1 expression on patients of hematologic malignancy following allogeneic hematopoietic stem cell transplantation. Zhonghua Nei Ke Za Zhi. 2008;47(7):578–81.
  110. Rossi G, Minervini MM, Carella AM, et al. Comparison between multiparameter flow cytometry and WT1-RNA quantification in monitoring minimal residual disease in acute myeloid leukemia without specific molecular targets. Leuk Res. 2012;36(4):401–6. doi: 10.1016/j.leukres.2011.11.020.
  111. Zhao Q, Zhao Q, Li Q, et al. Monitoring of WT1 and its target gene IRF8 expression in acute myeloid leukemia and their significance. Int J Lab Hematol. 2014;37(4):e67–71. doi: 10.1111/ijlh.12309.
  112. Mear J-B, Salaun V, Dina N, et al. WT1 and flow cytometry minimal residual disease follow-up after allogeneic transplantation in practice. 40th EBMT Meeting; 2014 30 March – 2 April; Milan, Italy; 2014: Abstract P655.
  113. Tamaki H, Ogawa H, Ohyashiki K, et al. The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. 1999;13(3):393–9. doi: 10.1038/sj.leu.2401341.
  114. Cilloni D, Gottardi E, Messa F, et al. Significant correlation between the degree of WT1 expression and the International Scoring System score in patients with myelodysplastic syndromes. J Clin Oncol. 2003;21(10):1988–95. doi: 10.1200/jco.2003.10.503.
  115. Bader P, Niemeyer C, Weber G, et al. WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelomonocytic leukemia. Eur J Haematol. 2004;73(1):25–8. doi: 10.1111/j.1600-2004.00260.x.
  116. Tamura H, Dan K, Yokose N, et al. Prognostic significance of WT1 mRNA and antiWT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes. Leuk Res. 2010;34(8):986–90. doi: 10.1016/j.leukres.2009.11.029.
  117. Yamauchi T, Matsuda Y, Takai M, et al. Wilms’ tumor-1 transcript in peripheral blood helps diagnose acute myeloid leukemia and myelodysplastic syndrome in patients with pancytopenia. Anticancer Res. 2012;32(10):4479–83.
  118. Qin Y-Z, Zhu H-H, Liu Y-R, et al. PRAME and WT1 transcripts constitute a good molecular marker combination for monitoring minimal residual disease in myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1442–9. doi: 10.3109/10428194.2012.743656.
  119. Ueda Y, Mizutani C, Nannya Y, et al. Clinical evaluation of WT1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1450–18. doi: 10.3109/10428194.2012.745074.
  120. Minetto P, Guolo F, Clavio M, et al. Combined assessment of WT1 and BAALC gene expression at diagnosis may improve leukemia-free survival prediction in patients with myelodysplastic syndrome. Leuk Res. 2015;39(8):866–73. doi: 10.1016/j.leukres.2015.04.011.
  121. Santamaria C, Ramos F, Puig N, et al. Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival. Ann Hematol. 2012;91(12):1887–95. doi: 10.1007/s00277-012-1538-
  122. Menssen HD, Renkl HJ, Rodeck U, et al. Presence of Wilms’ tumor gene wt1 transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia. 1995;9(6):1060–7.
  123. He YZ, Liang Z, Wu MR, et al. Overexpression of EPS8 is associated with poor prognosis in patients with acute lymphoblastic leukemia. Leuk Res. 2015;39(6):575–81. doi: 10.1016/j.leukres.2015.03.007.
  124. Xu B, Song S, Yip NC, et al. Simultaneous detection of MDR and WT1 gene expression to predict the prognosis of adult acute lymphoblastic leukemia. Hematology. 2010;15(2):74–80 doi: 10.1179/ 102453310X12583347009937.
  125. Azuma T, Otsuki T, Kuzushima K, et al. Myeloma cells are highly sensitive to the granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes. Clin Cancer Res. 2004;10(21):7402–12. doi: 10.1158/1078-ccr-04-0825.
  126. Hamalainen MM, Kairisto V, Junonen V, et al. Wilms tumour gene 1 overexpression in bone marrow as a marker for minimal residual disease in acute myeloid leukemia. Eur J Haematol. 2008;80(3):201–7. doi: 10.1111/j.1600-2007.01009.x.
  127. Wartheim GB, Bagg A. Minimal residual disease testing to predict relapse following transplant for AML and high-grade myelodysplastic syndromes. Expert Rev Mol Drug. 2011;11(4):361–6. doi: 10.1586/erm.11.19.
  128. Lambert J, Lambert J, Niboured O, et al. MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget. 2014;5(15):6280–8. doi: 10.18632/oncotarget.2196.
  129. Steinbach D, Bader P, Willasch A, et al. Prospective validation of a new method of monitoring minimal residual disease in childhood acute myeloid leukemia. Clin Cancer Res. 2014;21(6):1353–9. doi: 10.1158/1078-ccr-14-1999.
  130. Gray JX, McMillen L, Mollee P, et al. WT1 expression as a marker of minimal residual disease predicts outcome in acute myeloid leukemia when measured post-consolidation. Leuk Res. 2012;36(4):453–8. doi: 10.1016/j.leukres.2011.09.005.
  131. Noronha SA, Farrar JE, Alonzo TA, et al. WT1 expression at diagnosis does not predict survival in pediatric AML: a report from the children’s oncology group. Pediatr Blood Cancer. 2009;53(6):1136–9. doi: 10.1002/pbc.22142.
  132. Kim HJ, Choi EJ, Sohn HJ, et al. Combinatorial molecular marker assays of WT1, survivin, and TERT at initial diagnosis of adult acute myeloid leukemia. Eur J Haematol. 2013;91(5):411–22. doi: 10.1111/ejh.12167.
  133. Niavarani A, Currie E, Reyal Y, et al. APOBEC3A is implicated in a novel class of G-to-A mRNA editing in WT1 transcripts. PloS One. 2015;10(3):e0120089. doi: 10.1371/journal.pone.0120089.
  134. Taira C, Matsuda K, Kamijyo Y, et al. Quantitative monitoring of single nucleotide mutations by allele-specific quantitative PCR can be used for the assessment of minimal residual disease in patients with hematological malignancies throughout their clinical course. Clin Chim Acta. 2011;412(1–2):53–8. doi: 10.1016/j.cca.2010.09.011.
  135. Morita Y, Heike1 Y, Kawakami M, et al. Monitoring of WT1-specific cytotoxic T lymphocytes after allogeneic hematopoietic stem cell transplantation. Int J Cancer. 2006;119(6):1360–7. doi: 10.1002/ijc.21960.
  136. Tsuboi A, Oka Y, Nakajima H, et al. Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma. Int J Hematol. 2007;86(5):414–7. doi: 10.1007/bf02983998.
  137. Narita M, Masuko M, Kurasaki T, et al. WT1 peptide vaccination in combination with imatinib for a patient with CML in the chronic phase. Int J Med Sci. 2010;7(2):72–81. doi: 10.7150/ijms.7.72.

Low Dose Cytarabine and Cladribine for Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Clinical Experience

MYELOID TUMORS , , , , ,

SV Gritsaev, II Kostroma, AA Kuzyaeva, IM Zapreeva, EV Litvinskaya, LV Stel’mashenko, SA Tiranova, IS Martynkevich, NA Potikhonova, KM Abdulkadyrov

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

For correspondence: Sergei Vasil’evich Gritsaev, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kostroma II, Kuzyaeva AA, et al. Low Dose Cytarabine and Cladribine for Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Clinical Experience. Clinical oncohematology. 2016;9(1):48–53 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-48-53

ABSTRACT                                      

Aim. The aim of this paper is to evaluate the effectiveness of low dose cytarabine (Ara-C) combined with cladribine for the treatment of relapsed or refractory acute myeloid leukemia (AML) and to determine clinical and lab factors associated with response to the therapy.

Methods. Data of 10 patients aged 26–58 years (median 48 years) were analyzed. The diagnoses were de novo AML (7 patients), secondary AML (sAML) (2 patients) and refractory anemia with excess of blasts (RAEB-2) (1 patient). Four patients had primary refractory AML. Relapse was diagnosed in 3 patients. The induction scheme 7+3 was ineffective in patient with RAEB-2. There was no response to any kind of therapy in sAML patients. The treatment scheme under trial consisted of Ara-C 10–15 mg/m2 subcutaneously twice a day for 1–14 days and cladribine 5 mg/m2 intravenously once a day for 1–5 days. The course was repeated in case of at least two-fold decrease in bone marrow blasts level in a punctate versus baseline. Medical examination and maintenance therapy were performed in accordance with protocols approved by the clinic.

Results. According to the protocol, the patients received 1–2 courses. Response was achieved in 5 patients: 2 patients achieved complete response (CR) and 3 achieved partial response (PR). The most common complication was hematologic toxicity. All patients received transfusions of blood components. No lethal outcomes were observed within 8 weeks. The duration of the response was 2 to 3 months. During this period of time, allogeneic stem cell transplantation was performed in 2 patients with CR; however, in one patient, the conditioning regimen began at the same time with the increase in blast cell count in the bone marrow. The search for unrelated donors of hematopoietic stem cells for 2 patients with CR was begun. The distinct features of all patients with CR and PR were the following factors: de novo AML, absence of FLT3 or c-KIT mutations and the course duration was not less than 10 days.

Conclusion. Low dose Ara-C in combination with cladribine may be considered a treatment option for some patients with relapsed or refractory de novo AML.

Keywords: acute myeloid leukemia, relapse, refractory, chemotherapy, low dose cytarabine, cladribine.

Received: June 4, 2015

Accepted: October 8, 2015

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REFERENCES

  1. Weick JK, Kopecky KJ, Appelbaum FR, et al. A randomized investigation of high dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996;88(8):2841–51.
  2. Tallman MS, Gilliland G, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106(4):1154–63. doi: 10.1182/blood-2005-01-0178.
  3. Estey EH. Acute myeloid leukemia: 2014 update on risk-stratification and management. Am J Hematol. 2014;89(11):1063–81. doi: 10.1002/ajh.23834.
  4. Yanada M, Garcia-Manero G, Borthakur G, et al. Potential cure of acute myeloid leukemia. Cancer. 2007;110(12):2756–60. doi: 10.1002/cncr.23112.
  5. Mangan JK, Luger SM. Salvage therapy for relapsed or refractory acute myeloid leukemia. Ther Adv Hematol. 2011;2(2):73–82. doi: 10.1177/2040620711402533.
  6. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Национальные клинические рекомендации по диагностике лечению острых миелоидных лейкозов взрослых. Гематология и трансфузиология 2014;59(1):3–29.
    [Savchenko VG, Parovichnikova EN, Afanas’ev BV, et al. National clinical recommendations for diagnosis and treatment of acute myeloid leukemias in adults. Gematologiya i transfuziologiya. 2014;59(1):3–29. (In Russ)]
  7. Грицаев С.В., Мартынкевич И.С., Зюзгин И.С. и др. Гетерогенность острого миелоидного лейкоза с транслокацией t(8;21)(q22;q22). Терапевтический архив. 2014;86(7):45–52.
    [Gritsaev SV, Martynkevich IS, Zyuzgin IS, et al. Heterogenicity of acute myeloid leukemia with t(8;21)(q22;q22) translocation. Terapevticheskii arkhiv. 2014;86(7):45–52. (In Russ)]
  8. Milligan DW, Grimwade D, Cullis JO, et al. Guidelines on the management of acute myeloid leukemia in adults. Br J Haematol 2006; 135(4): 450–74. doi: 10.1111/j.1365-2141.2006.06314.x.
  9. Fey MF, Buske C. Acute myeloblastic leukemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl. 6):138–43. doi: 10.1093/annonc/mdt320.
  10. Parker WB, Bapat AR, Shen JX, et al. Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase. Mol Pharmacol. 1988;34(4):485–91.
  11. Hirota Y, Yoshioka A, Tanaka S, et al. Imbalance of deoxyribonucleoside triphosphates, DNA double-strand breaks, and cell death caused by 2-chlorodeoxyadenosine in mouse FM3A cells. Cancer Res. 1989;49(4):915–9.
  12. Wrzesien-Kus A, Robak T, Lech-Maranda E, et al. A multicenter, open, non-comparative, phase II study of the combination of cladribine, cytarabine, and G-CSF and induction therapy in refractory acute myeloid leukemia – a report of the Polish Adult Leukemia Group (PALG). Eur J Hematol. 2003;71(3):155–62. doi: 10.1034/j.1600-0609.2003.00122.x.
  13. Price SL, Lancet JE, George TJ, et al. Salvage chemotherapy regimens for acute myeloid leukemia: Is one better? Efficacy comparison between CLAG and MEC regimens. Leuk Res. 2011;35(3):301–4. doi: 10.1016/j.leukres.2010.09.002.
  14. Kern W, Schleyer E, Braess J, et al. Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias. Ann Hematol. 2001;80(6):334–9. doi: 10.1007/s002770100293.
  15. Hashmi KU, Khan B, Ahmed P, et al. FLAG-IDA in the treatment of refractory/relapsed acute leukaemias: single centre study. J Pak Med Assoc. 2005;55(6):234–8.
  16. Pastore D, Specchia G, Carluccio P, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003;82(4):231–5.
  17. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642–9. doi: 10.1200/jco.2003.04.036.
  18. Breems DA, van Putten WLJ, Huijgens PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005;23(9):1969–78. doi: 10.1200/jco.2005.06.027.
  19. Breems DA, van Putten WL, de Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29):4791–7. doi: 10.1200/jco.2008.16.0259.
  20. Armistead PM, de Lima M, Pierce S, et al. Quantifying the survival benefit for allogeneic stem cell transplantation in relapsed acute myeloid leukemia. Biol Blood Marrow Transplant. 2009;15(11):1431–8. doi: 10.1016/j.bbmt.2009.07.008.
  21. Kurosawa S, Yamaguchi T, Miyawaki S, et al. Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse. Haematologica. 2010;95(11):1857–64. doi: 10.3324/haematol.2010.027516.
  22. Mangan JK, Luger SM. Salvage therapy for relapsed or refractory acute myeloid leukemia. Ther Adv Hematol. 2011;2(2):73–82. doi: 10.1177/2040620711402533.
  23. Freyer CW, Gupta N, Wetzler M, Wang ES. Revisiting the role of cladribine in acute myeloid leukemia: an improvement on past accomplishments or more old news? Am J Hematol. 2015;90(1):62–72. doi: 10.1002/ajh.23862.
  24. Zhang WG, Wang FX, Chen YX, et al. Combination chemotherapy with low-dose cytarabine, homoharringtonine, and granulocyte colony-stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia. Am J Hematol. 2008;83(3):185–8. doi: 10.1002/ajh.20903.
  25. Liu L, Zhang Y, Jin Z, et al. Increasing the dose of aclarubicin in low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) can safely and effectively treat relapsed or refractory acute myeloid leukemia. Int J Hematol. 2014;99(5):603–8. doi: 10.1007/s12185-014-1528-8.
  26. Assouline S, Culjkovic-Kraljacic B, Bergeron J, et al. A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E. Haematologica. 2015;100(1):e7–9. doi: 10.3324/haematol.2014.111245.

Surgical Treatment of Perianal Infectious Complications in Hematologic Clinic

SURGICAL COMPLICATIONS IN ONCOHEMATOLOGY , , , ,

S.V. Shtyrkova, S.R. Karagyulyan, K.I. Danishyan, S.K. Kravchenko, V.V. Troitskaya, L.A. Kuz’mina

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Svetlana Vital’evna Shtyrkova, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-91; e-mail: sv-styrkova@mail.ru

For citation: Shtyrkova S.V., Karagyulyan S.R., Danishyan K.I., Kravchenko S.K., Troitskaya V.V., Kuz’mina L.A. Klin. Onkogematol. 2015; 8(3): 337-42. (In Russ.)

ABSTRACT

Background & Aims. In general surgical practice, the perianal infection is considered an emergency surgical defect and requires an urgent surgical intervention. However, the perianal infection complicating leukemia has its peculiar clinical manifestations and requires revision of the traditional approach. The aim of the study is to mark out possible risk factors of development of the perianal infection in patients with hematologic malignancy and to estimate efficacy of various treatment options.

Methods. Results of examination and treatment of 143 oncohematological patients with inflammatory anorectal pathology are presented. Among them, the largest group consisted of 110 patients with anal fissures and fistulas.

Results. The study demonstrated that the main mechanism of infection in these patients was associated with local damage of the wall of the anal canal: mechanical trauma ® crack ® paraproctitis or inflammation due to diarrhea or toxic effects of drugs ® anusitis ® cryptitis ® paraproctitis. In case of paraproctitis in patients with leukopenia, a combined parenteral antibiotic therapy is considered to be the basic treatment method.

Conclusion. In oncohematological patients when the underlying disease as well as the upcoming chemotherapy can lead to severe immunosuppression, the presence of persistent defect of the anal canal wall (anal fissure, fistula) should be considered as an indication for surgery. The surgical procedure reduces the risk of local inflammation and septic complications.

Keywords: perianal infection, disease of the anal canal, hematologic malignancies, leukemia, chemotherapy.

Received: May 19, 2015

Accepted: June 3, 2015

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REFERENCES

  1. North JH, Weber ThK, Rodriguez-Bigas MA, et al. The Management of Infectious and Noninfectious Anorectal Complications in Patients with Leukemia. J Am Coll Surg 1996;183(4):322–8.
  2. Grewall H, Giullem JG, Quan SH, Enker WE. Anorectal Disease in Neutropenic leukemic Patients. Operative vs. Nonoperative management. Dis Colon Rect. 1994;37(11):1095–9. doi: 10.1007/bf02049810.
  3. Buyukasic Y, Ozecebe O, Sayinalp N, et al. Perianal infection in Patients with Leukemia. Importance of the Course of Neutrophil Count. Dis Colon Rect. 1998;41(1):81–5. doi: 10.1007/bf02236900.
  4. Troiani RT, DuBois JJ, Boyle L. Surgical management of anorectal infection in the leukemic patient. Mil Med. 1991;156(10):558–61.
  5. Vanheuvertzvin R, Delannoy A, Michaux JL, Dive C. Anal lesions in Hematologic Diseases. Dis Colon Rect. 1980;23(5):310–2. doi: 10.1007/bf02586835.
  6. Prager D, Indru T, Khubchandani MD, et al. Proctologic Disorders and Hematologic Diseases. Dis Colon Rect. 1971;14(1):4–11. doi: 10.1007/bf02553167.
  7. Chirletti P, Beverati M, Apice N, et al. Prophylaxis and treatment of inflammatory anorectal complications in leukemia. Ital J Surg Sci. 1988;18(1):45–8.
  8. Chen CY, Cheng A, Huang SY, et al. Clinical and microbiological characteristics of perianal infections in adult patients with acute leukemia. PLoS One. 2013;8(4). doi: 10.1371/journal.pone.0060624.
  9. Lehrnbecher T, Marshall D, Gao C, Chanock SJ. A Second Look at Anorectal Infections in Cancer Patients in a Large Cancer Institute: The Success of Early Intervention with Antibiotics and Surgery. Infection. 2002;30(5):272–6. doi: 10.1007/s15010-002-2197-8.
  10. Carlson GW, Ferguson CM, Amerson JR. Perianal infection in acute leukemia. Am Surg. 1988;54:693–5.
  11. Glenn J, Cotton D, Wesley R, Pizzo Ph. Anorectal infections in patients with malignant diseases. Rev Infect Dis. 1988;10(1):42–52. doi: 10.1093/clinids/10.1.42.
  12. Corfitsen MT, Hansen CP, Christensen TH, Kaae HH. Anorectal abscesses in immunosuppressed patients. Eur J Surg. 1992;158(1):51–3.
  13. Berg A, Armitage JO, Burns CP. Fournier’s gangrene complicating aggressive therapy for hematologic malignancy. Cancer. 1986;57(12):2291–4. doi: 10.1002/1097-0142(19860615)57:12<2291::aid-cncr2820571210>3.0.co;2-4.
  14. Shake AA, Shinar E, Freund H. Managing the granulocitopenic patients with acute perianal inflammatory disease. Am J Surg. 1986;152(5):510–2. doi: 10.1016/0002-9610(86)90217-5.

Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study

AUTOIMMUNE THROMBOCYTOPENIA, LYMPHOID TUMORS , , ,

IA Kryachok1, AA Amdiev2, IB Titorenko1, EM Aleksik1, EO Ul’yanchenko1, OI Novosad1, ES Filonenko1, MI Kasich2, MYa Kiseleva2

1 National Cancer Institute, 33/43 Lomonosova str., Kyiv, Ukraine, 03022

2 V.M. Efetov Crimean National Clinical Oncology Dispensary, 49a Bespalova str., Simferopol, Russian Federation, 295023

For correspondence: Alim Anvarovich Amdiev, 49a Bespalova str., Simferopol, Russian Federation, 295023; Tel.: +38(0652)60-22-09; e-mail: amdiev@gmail.com

For citation: Kryachok IA, Amdiev AA, Titorenko IB, et al. Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study. Clinical oncohematology. 2015;8(3):281–6 (In Russ).

ABSTRACT

Objective. To study the efficacy and toxicity of various treatment schemes for patients with intermediate-risk Hodgkin’s lymphoma (HL).

Methods. This article presents an analysis of the immediate results of complex treatment of 103 intermediate-risk HL patients (stage IIA and IIB with one or more unfavorable prognostic factors), who have been treated at the National Cancer Institute (Kyiv) and the Crimean Oncology Dispensary (Simferopol) from 2009 to 2014 (study group). Patients were divided into two study groups and treated with 6xBEACOPP-esc or 2xBEACOPP-esc + 4xABVD, followed by radiotherapy on the affected areas at a dose of 30–36 Gy in both groups. The control group included 53 patients who received treatment according to the 6xABVD scheme, followed by radiotherapy on the affected areas at a dose of 30–36 Gy over the period from 2000 to 2008. The immediate efficiency of the therapy, as well as its toxicity was evaluated.

Results. The study results demonstrated that treatment of the intermediate-risk HL patients that included 6xBEACOPP-esc and 2xBEACOPP-esc + 4xABVD proved to be an effective approach. Overall immediate efficacy of 2xBEACOPP-esc + 4xABVD protocol with subsequent radiation therapy was 95.83 %, and that of the 6xBEACOPP-esc was 96.36 %, which was significantly higher than the efficacy in the control group (83.02 %; p < 0.05). The toxicity level of the therapy was lower in the 2xBEACOPP-esc + 4xABVD group than that in the 6xBEACOPP-esc group (63.19 % and 83.03 %, respectively, p < 0.001).

Conclusion. Treatment of patients with intermediate-risk HL with 2xBEACOPP-esc + 4xABVD is comparable to that with 6xBEACOPP-esc, but it demonstrates a better toxicity profile.

Keywords: Hodgkin’s lymphoma, chemotherapy, efficacy, toxicity.

Received: March 31, 2015

Accepted: May 31, 2015

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REFERENCES

  1. Diehl V, ed. 25 Years German Hodgkin Study Group. Medizin & Wissen; 2004.
  2. Демина Е.А. Лимфома Ходжкина: от Томаса Ходжкина до наших дней. Клиническая онкогематология. 2008;1(2):114–8.
    [Demina EA. Hodgkin’s lymphoma: from Thomas Hodgkin till present days. Klinicheskaya onkogematologiya. 2008;1(2):114–8. (In Russ)]
  3. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348(24):2386–95. doi: 10.1056/nejmoa022473.
  4. Федоренко З.П., Гайсенко А.В., Гулак Л.О. [та ін.] Рак в Украiні, 2009–2010. Захворюваність, смертність, показники діяльності онкологічноi служби. Бюл. Національного канцер-ре’стру Украiни. 2011;12:73–4.
    [Fedorenko ZP, Gaisenko AV, Gulak LO, et al. Cancer in Ukraine, 2009–2010. Morbidity and mortality rates and cancer service performance indicators. Byulleten’ Natsіonal’nogo kantser-re’stru Ukraini. 2011;12:73–4. (In Ukr.)]
  5. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 Study. J Clin Oncol. 2009;27(27):4548–54. doi: 10.1200/jco.2008.19.8820.
  6. Lister TA. Staging for Hodgkin’s disease. Semin Oncol. 1990;17(6):696–703.
  7. Aleman BM, Raemaekers JM, Tirelli U, et al. Involved-field radiotherapy for advanced Hodgkin’s lymphoma. N Engl J Med. 2003;348(24):2396–406. doi: 10.1056/nejmoa022628.
  8. Bonadonna G, Zucali R, Monfardini S, et al. Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975;36(1):252–9. doi: 10.1002/1097-0142(197507)36:1<252::aid-cncr2820360128>3.0.co;2-7.
  9. Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results. J Clin Oncol. 2004;22(14):2835–41. doi: 10.1200/jco.2004.12.170.
  10. Engert A, Plutschow A, Eich HT, et al. Reduced Treatment Intensity in Patients with Early-Stage Hodgkin’s Lymphoma. N Engl J Med. 2010;363(7):640–52. doi: 10.1056/nejmoa1000067.
  11. Horning SJ. Risk, cure and complications in advanced Hodgkin disease. ASH Educ Program. 2007;1:197–203. doi: 10.1182/asheducation-2007.1.197.
  12. Horning SJ, Hoppe RT, Advani R, et al. Efficacy and late effects of Stanford V chemotherapy and radiotherapy in untreated Hodgkin’s disease: mature data in early and advanced stage patients. Blood. 2004;104:92a, abstract 308.
  13. Diehl V, Haverkamp H, Mueller RP, et al. Eight Cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): final analysis of the randomised HD12 trial of the German Hodgkin Study Group (GHSG). Blood. 2008;112(11): Abstract 1558.
  14. Sieber M, Bredenfeld H, Josting А, et al. 14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced stage Hodgkin’s lymphoma: results of a pilot study of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol. 2003;21(9):1734–9. doi: 10.1200/jco.2003.06.028.
  15. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trail): a randomised, open-label, phase 3 non-inferiority trail. The Lancet. 2012;379(9828):1791–9. doi: 10.1016/s0140-6736(11)61940-5.
  16. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.
  17. Engert A, Franklin J, Eich HT, et al. Two cycles of ABVD plus extended field radiotherapy is superior to radiotherapy alone in early-favorable Hodgkin lymphoma: final results of the GHSG HD7 Trial. J Clin Oncol. 2007;10(10):3495–502. doi: 10.1200/jco.2006.07.0482.
  18. Engert A, Diehl V, Pluetschow A, et al. Two cycles of ABVD followed by involved field radiotherapy with 20 Gray (Gy) the new standard of care in the treatment of patients with early-stage Hodgkin lymphoma: final analysis of the randomized German Hodgkin Study Group (GHSG) HD10. Blood. 2009;114: Abstract 716.
  19. Diehl V, Franklin J, Pfistner B, Engert A. German Hodgkin Study Group. Ten-year results of a German Hodgkin Study Group randomized trial of standart and increased dose BEACOPP chemotherapy for advanced Hodgkin lymphoma (HD9). J Clin Oncol (Meeting Abstracts). 2007;25(Suppl 18):LBA8015.

Importance of biochemical studies of brain natriuretic peptide in patients with diffuse large B-cell lymphoma

LABORATORY DIAGNOSIS , , ,

M.O. Yegorova, Ye.N. Komolova, and S.Ye. Samsonova

Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

ABSTRACT

In this study, we measured the levels of the brain natriuretic peptide (BNP) in the blood of patients with diffuse large B-cell lymphoma (DBCL) before and after polychemotherapy. The study included 10 patients: 6 males and 4 females at the age of 39 to 63 (mean age = 51 ± 12). The control group consisted of 20 virtually healthy donors. It was shown that measurements of BNP plasma levels in DBCL could identify the patients with the high risk of heart failure. Screening tests with determination of BNP levels can influence the choice of chemotherapy for DBCL.

Keywords: diffuse large B-cell lymphoma, chemotherapy, BNP, myocardial infarction, congestive left ventricular heart failure.

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REFERENCES

  1. Морозова А.К., Звонков Е.Е., Кременецкая А.М. и др. Первый опыт применения модифицированной программы NHL-BFM-90 при лечении пер- вичной диффузной B-крупноклеточной лимфосаркомы костей и мягких тканей с факторами неблагоприятного прогноза. Тер. арх. 2009; 7: 61–5. [Morozova A.K., Zvonkov Ye.Ye., Kremenetskaya A.M., et al. Initial experience with using modified NHL-BFM-90 program in management of primary diffuse large B-cell lymphosarcoma of bones and soft tissues with unfavorable prognostic factors. Ter. arkh. 2009; 7: 61–5. (In Russ.)].
  2. Myers C. The Role of Iron in Doxorubicin-Induced Cardiomyopathy. Sem. Oncol. 1998; 25(4 Suppl. 10): 10–4.
  3. Орел Н.Ф. Кардиотоксичность антрациклинов: возможности преодо- ления. Совр. онкол. 2004; 3: 121–4. [Orel N.F. Cardiotoxicity of anthracyclines: potential overcoming. Sovr. onkol. 2004; 3: 121–4. (In Russ.)].
  4. Bhardwaj A., Rehman S.U., Mohammed A. et al. Design and methods of the Pro-B Type Natriuretic peptide outpatient tailored chronic heart failure therapy (PROTECT) Study. Am. Heart J. 2010; 159: 532–8.el.
  5. Maisel A.S., Krishnaswamy P., Nowak R.M. et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N. Engl. J. Med. 2002; 347: 161–7.
  6. Sadanandan S., Cannon C.P., Chekuri K. et al. Association of elevated B-type natriuretic peptide levels with angiographic findings among patients with unstable angina and non-ST-segment elevation myocardial infarction. J. Am. Coll. Cardiol. 2004; 44: 564–8.
  7. Елисеев О.М. Натрийуретические пептиды: эволюция знаний. Тер. арх. 2003; 9: 40–5. [Yeliseyev O.M. Natriuretic peptides: knowledge evolution. Ter. arkh. 2003; 9: 40–5. (In Russ.)].
  8. Gackowskia A., Isnarda R., Golmardc J.-L. et al. Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure. Eur. Heart J. 2004; 25: 1788–96.
  9. Days J., Lehman R., Glasziou P. The Role of BNP Testing in Heart Failure. Am. Fam. Phys. 2006; 74(11): 1893–900.
  10. Harrison A., Morrison L.K., Krishnaswamy P. et al. B-Type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann. Emerg. Med. 2002; 39: 131–8.
  11. Leya F.S., Arab D., Joyal D. et al. The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy. J. Am. Coll. Cardiol. 2005; 45: 1900–2.

Pulmonary MALT-lymphoma: case report and literature review

LYMPHOID TUMORS , ,

A.K. Morozova, N.G. Gabeeva, and E.E. Zvonkov

Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

ABSTRACT

This article presents a rare case of pulmonary MALT-lymphoma and literature review. An elderly patient with pulmonary MALT lymphoma was successfully treated according to R-B (rituximab + bendamustine) chemotherapy program. After 6 R-B courses, sustained remission with minimal toxicity and good tolerability was achieved.

Keywords: pulmonary MALT-lymphoma, chemotherapy, bendamustine

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REFERENCES

  1. Cadranel J., Wislez M., Antoine M. et al. Primary pulmonary lymphoma. Eur. Respir. 2002; 20: 750–62.
  2. Isaacson P., Wright D.H. Malignant lymphoma of mucosa associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983; 52: 1410–6.
  3. Zinzani P.L., Vittorio Stefoni V., Musuraca G. et al. Fludarabine-Containing Chemotherapy as Frontline Treatment of Nongastrointestinal Mucosa-Associated Lymphoid Tissue Lymphoma. Cancer 2004; 100(10): 2190–4.
  4. Hui H., Zhi-wei L., Chun-guo J. et al. Clinical and prognostic characteristics of pulmonary mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 23 cases in a Chinese population. Med. J. 2011; 124(7): 1026–30.
  5. Воробьев А.И. Руководство по гематологии. Т. 2. М.: Ньюдиамед, 2003: 92–100. [Vorobyev A.I. Rukovodstvo po gematologii. T. 2 (Manual of hematology, Vol. 2). M.: Nyudiamed, 2003: 92–100.]
  6. Программное лечение заболеваний системы крови. Под ред. В.Г. Сав- ченко. Т. 2. М.: Практика, 2012: 579–93. [Programmnoye lecheniye zabolevaniy sistemy krovi. Pod red. V.G. Savchenko. T. 2 (Program therapy for hematological disorders. Ed. by V.G. Savchenko. 2). M.: Praktika, 2012: 579–93.]
  7. Zvonkov E., Krasilnikova B., Magomedova A. et al. FMC/FMC-R regimens efficiency in treatment primary extragastric MALT-lymphomas. Abstract book 2007; 92(1): 444.
  8. Красильникова Б.Б., Звонков Е.Е., Кравченко С.К. и др. Первый опыт применения программ FNC и FNC-R в лечении первичной лимфоцитомы орбиты. Гематол. и трансфузиол. 2008; 6: 3–7. [Krasilnikova B.B., Zvonkov Ye.Ye., Kravchenko S.K. i dr. Pervyy opyt primeneniya programm FNC i FNC-R v lechenii pervichnoy limfotsitomy orbity (Initial experience with FNC and FNC-R programs usage in therapy for primary orbital lymphocytoma. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2008; 6: 3–7.]
  9. Yoon R.G., Kim M.Y., Songb J.W. Primary Endobronchial Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue: CT Findings in 7 Patients. Korean J. Radiol. 2013; 14(2): 366–74.
  10. Zucca E., Conconi A., Laszlo D. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study. Clin. Oncol. 2013; 31(5): 565–72.
  11. Domingo S., Canales M., Nicolas C. et al. Bendamustine and rituximab as first line treatment for patients with MALT lymphoma. An interim report of a phase 2 trial in Spain (MALT-2008–10). 11th International Conference on Malignant Lymphoma. Lugano, 2011. Abstract 299.
  12. Cordier J.F., Chailleux E., Lauque D. Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients. Chest 1993; 103(1): 201–8.
  13. Imai Н., Sunaga N., Kaira K. et al. Clinicopathological Features of Patients with Bronchial-Associated Lymphoid Tissue Lymphoma. Med. 2009; 48: 301–6.
  14. Thieblemont C., Berger F., Dumontet C. et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2013; 2000(95): 802–6.
  15. Borie R., Wislez M., Thabut G. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Respir. J. 2009; 34: 1408–16.
  16. Troch M., Streubel B., Petkov V. et al. Does MALT Lymphoma of the Lung Require Immediate Treatment? An Analysis of 11 Untreated Cases with Longterm Follow-up. Anticancer Res. 2007; 27: 3633–8.
  17. Zinzani P.L., Magagnoli M., Galieni P. et al. Nongastrointestinal LowGrade Mucosa-Associated Lymphoid Tissue Lymphoma: Analysis of 75 Patients. Clin. Oncol. 1999; 17: 1254–8.
  18. Kocaturk C.I., Seyhan E.C., Zeki M. et al. Primary pulmonary nonHodgkin’s lymphoma: ten cases with a review of the literature. Toraks. 2012; 60(3): 246–53.
  19. Zinzani P.L., Pellegrini C., Gandolfi L. et al. Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantronecontaining regimens. Oncol. 2012 Dec 5. doi: 10.1002/hon.2039.
  20. Brown J.R., Friedberg J.W., Feng Y. et al. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. J. Haematol. 2009; 145(6): 741–8.
  21. Prabhash K., Vikram G.S., Nair R. et al. Fludarabine in lymphoproliferative malignancies: a single-centre experience. Med. J. India 2008; 21(4): 171–4.
  22. Rummel M.J., Kaiser U., Balser C. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas — Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting Abstracts 2010; 116: 856.
  23. Rummel M.J., Niederle N., Maschmeyer G. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 noninferiority trial. Lancet, Early Online Publication, 20 February 2013. doi: 10.1016/ S0140-6736(12)61763.