AUTOIMMUNE THROMBOCYTOPENIA

Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis

AUTOIMMUNE THROMBOCYTOPENIA , ,

DI Chebotarev, AM Kovrigina, AL Melikyan

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

For correspondence: Dmitrii Ilich Chebotarev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)091-27-09; e-mail: chebadmitry@gmail.com

For citation: Chebotarev DI, Kovrigina AM, Melikyan AL. Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis. Clinical oncohematology. 2022;15(1):76–84. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-76-84

ABSTRACT

Background. As morphological pattern of bone marrow (BM) biopsy samples at advanced stages of clonal evolution in essential thrombocythemia (ET) appears similar to that in the development of post-thrombocythemic myelofibrosis and primary myelofibrosis (PMF), the expression of fibrogenesis factors by atypical megakaryocytes (MKC) acquires increased interest.

Aim. To study the expression of the transforming growth factor TGFβF1 by atypical MKC; to relate the number of TGFβF1-positive MKCs with the degree of BM stroma fibrosis and trabecular bone changes in patients with ET and different PMF stages.

Materials & Methods. BM biopsy samples of ET and PMF patients, obtained before cytoreductive therapy, were subjected to histochemical study with Gomori stain and Masson trichrome as well as to CD42b and TGFβF1 antibody immunohistochemical assays. The degree of myelofibrosis and osteosclerosis was estimated by semi-quantitative method in accordance with the European Consensus guidelines. The morphological characteristics of atypical MKC included the comparative evaluation of nuclear-cytoplasmic ratio.

Results. The number of MKCs with high nuclear-cytoplasmic ratio was significantly higher in BM biopsy samples of patients with pre-fibrosis/early PMF (pre-PMF) stage and fibrosis stage of PMF (f-PMF) compared with BM biopsy samples of ET patients. The analysis of TGFβF1 expression showed different numbers of positive MKCs in the study groups. The matching of the number of TGFβF1-positive MKCs with the degree of myelofibrosis and osteosclerosis, with no regard to nosologic entities, revealed significant moderate correlation between these features (r = 0.431, p = 0.001 и r = 0.499, p = 0.001, respectively). In 55 % of pre-PMF patients’ BM biopsy samples, histochemical study with Masson trichrome stain visualized minimal immature osteoid deposits on bone trabeculae. Similar changes were also identified in f-PMF patients’ BM biopsy samples, whereas the ET patients’ samples featured none of them.

Conclusion. The results of the study prove that the pathological clone of MKC with TGFβF1 expression affects myelofibrosis and osteosclerosis processes whose manifestation in BM biopsy samples is associated with the number of TGFβF1-expressing atypical MKCs.

Keywords: primary myelofibrosis, pre-fibrosis and fibrosis stages, essential thrombocythemia, osteosclerosis, TGFβF1, pathomorphology, immunohistochemistry.

Received: August 12, 2021

Accepted: November 30, 2021

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REFERENCES

  1. Swerdlow S, Campo E, Harris N, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. рр. 174–7.
  2. Kreipe H, Busche G, Bock O, Hussein K. Myelofibrosis: molecular and cell biological aspects. Fibrogen Tiss Repair. 2012;5(Suppl 1):S21. doi: 10.1186/1755-1536-5-S1-S21.
  3. Buhr T, Choritz H, Georgii A. The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia. Virchows Arch A Pathol Anat Histopathol. 1992;420(6):473–8. doi: 10.1007/BF01600251.
  4. Martyre MC. Platelet PDGF and TGF-β Levels in Myeloproliferative Disorders. Leuk Lymphoma. 1991;6(1):1–6. doi: 10.3109/10428199109064872.
  5. Wang JC. Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia. Leuk Lymphoma. 2005;46(9):1261–8. doi: 10.1080/10428190500126463.
  6. Bock O, Loch G, Schade U, et al. Aberrant expression of transforming growth factor beta-1 (TGF beta-1) per se does not discriminate fibrotic from non-fibrotic chronic myeloproliferative disorders. J Pathol. 2005;205(5):548–57. doi: 10.1002/path.1744.
  7. Agarwal A, Morrone K, Bartenstein M, et al. Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell Investig. 2016;3:5. doi: 10.3978/j.issn.2306-9759.2016.02.03.
  8. Jacquelin S, Kramer F, Mullally A, Lane SW. Murine Models of Myelofibrosis. Cancers (Basel). 2020;12(9):2381. doi: 10.3390/cancers12092381.
  9. Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.
  10. Krystal G, Lam V, Dragowska W, et al. Transforming growth factor beta 1 is an inducer of erythroid differentiation. J Exp Med. 1994;180(3):851–60. doi: 10.1084/jem.180.3.851.
  11. Wickenhauser C, Hillienhof A, Jungheim K, et al. Detection and quantification of transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) release by normal human megakaryocytes. Leukemia. 1995;9(2):310–5.
  12. Sennikov SV, Eremina LV, Samarin DM, et al. Cytokine gene expression in erythroid cells. Eur Cytokine Netw. 1996;7(4):771–4.
  13. Di Giandomenico S, Kermani P, Molle N, et al. Megakaryocyte TGFβ1 partitions erythropoiesis into immature progenitor/stem cells and maturing precursors. Blood. 2020;136(9):1044–54. doi: 10.1182/blood.2019003276.
  14. Tang Y, Hu M, Xu Y, et al. Megakaryocytes promote bone formation through coupling osteogenesis with angiogenesis by secreting TGF-β Theranostics. 2020;10(5):2229–42. doi: 10.7150/thno.40559.
  15. Malara A, Abbonante V, Zingariello M, et al. Megakaryocyte contribution to bone marrow fibrosis: many arrows in the quiver. Mediterr J Hematol Infect Dis. 2018;10(1):e2018068. doi: 10.4084/MJHID.2018.068.
  16. Bonewald LF, Mundy GR. Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res. 1990;250:261–76. doi: 10.1097/00003086-199001000-00036.
  17. Wu M, Chen G, Li YP. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4(1):16009. doi: 10.1038/boneres.2016.9.
  18. Jann J, Gascon S, Roux S, Faucheux N. Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions. Int J Mol Sci. 2020;21(20):7597. doi: 10.3390/ijms21207597.
  19. Zhang Z, Zhang X, Zhao D, et al. TGF β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. Mol Med Rep. 2019;19(5):3505–18. doi: 10.3892/mmr.2019.10051.
  20. Murshed M. Mechanism of Bone Mineralization. Cold Spring Harb Perspect Med. 2018;8(12):a031229. doi: 10.1101/cshperspect.a031229.
  21. Чеботарев Д.И., Ковригина А.М., Меликян А.Л., Кузьмина Л.А. Сравнительная характеристика изменений клеточного состава, стромы костного мозга и трабекулярной кости при трансплантации аллогенных гемопоэтических стволовых клеток у больных первичным миелофиброзом. Гематология и трансфузиология. 2021;66(1):68–78. doi: 10.35754/0234-5730-2021-66-1-68-78.
    [Chebotarev DI, Kovrigina AM, Melikyan AL, Kuzmina LA. Comparative characteristics of bone marrow cell composition, stroma, and trabecular bone in allogenic hematopoietic stem cell transplantation in patients with primary myelofibrosis. Russian journal of hematology and transfusiology. 2021;66(1):68–78. doi: 10.35754/0234-5730-2021-66-1-68-78. (In Russ)]
  22. Szuber N, Mudireddy M, Nicolosi M, et al. 3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups. Mayo Clin Proc. 2019;94(4):599–610. doi: 10.1016/j.mayocp.2018.08.022.

Current State of Diagnosis and Treatment of Acute Myeloid Leukemias in Adult Patients in the Republic of Kazakhstan

AUTOIMMUNE THROMBOCYTOPENIA ,

AA Klodzinskii1, IA Pivovarova1, LG Turgunova2, AZh Anafina2, AV Zinchenko1

1 Center for Hematology, branch of Karaganda Center for Hematology, 41/43 Erubaeva str., Karaganda, Republic of Kazakhstan, 100012

2 Medical University of Karaganda, 40 Gogolya str., Karaganda, Republic of Kazakhstan, 100008

For correspondence: Aimzhan Zharkynovna Anafina, 40 Gogolya str., Karaganda, Republic of Kazakhstan, 100008; Tel.: +7(701)493-54-16; e-mail: aimzhan_31_08@mail.ru

For citation: Klodzinskii AA, Pivovarova IA, Turgunova LG, et al. Current State of Diagnosis and Treatment of Acute Myeloid Leukemias in Adult Patients in the Republic of Kazakhstan. Clinical oncohematology. 2022;15(1):69–75. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-69-75

ABSTRACT

Background. In recent years, the incidence of acute myeloid leukemias (AML) globally has continued to increase. Current approaches to AML treatment remain a challenge for the healthcare in many countries. There are only single studies on the analysis of AML state in adult patients in Kazakhstan. Over the last 10 years in Kazakhstan, no results of AML monitoring in adult patients have been available.

Aim. To study the characteristics of clinical course and treatment outcomes in AML in the Central Kazakhstan and in the city of Ust-Kamenogorsk, East Kazakhstan Region.

Materials & Methods. The study enrolled 86 AML patients (46 men and 40 women), the median age was 60.5 years (range 19–86 years); 64 (74.4 %) patients were from Karaganda Region, 15 (17.4 %) patients were from Ust-Kamenogorsk, and 7 (8.1 %) patients were from other regions of Kazakhstan. The analysis covered the structure and treatment outcomes in newly diagnosed AML patients within the period from 2018 to June, 2021. Statistical analysis of data was made using SPSS Statistics 23.0.

Results. The analysis of diagnostic techniques showed that myelogram and immunophenotyping were used in 98.8 %, cytogenetic assay was made in 18 %, and molecular analysis was performed in 59.3 % of patients. The “7+3” remission induction was administered in 54.6 % of patients, 20.9 % of patients were treated with hypomethylating agents and low doses of cytarabine, and 24.4 % of patients were on palliative and supportive therapy. Out of 47 patients treated with the “7+3” remission induction, complete clinical hematological remission was reached in 29 (61.7 %) patients. Primary resistance was reported in 21.3 % of patients. Early mortality (death within 30 days from the start of induction) rate was 17 %. High-dose cytarabine consolidation (1.5–3 g/m2 twice every other day, 2–3 courses) was administered to 75.8 % of patients. All the allogeneic bone marrow transplantations (n = 7) were performed at the National Research Center for Oncology and Transplantology in Nur-Sultan. The median overall survival in the group of standard “7+3” chemotherapy recipients was 11 months (range 1–83 months), and the median disease-free survival was 9 months (range 2–79 months).

Conclusion. The study presents the characteristics and short-term outcomes of treatment of adult AML patients in Kazakhstan. The study limitations were a short follow-up period and enrollment of patients only from two regions of Kazakhstan. It is necessary to continue improving the current standards of AML diagnosis and treatment of adult patients.

Keywords: Kazakhstan, acute myeloid leukemias, diagnosis, treatment.

Received: September 7, 2021

Accepted: December 10, 2021

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REFERENCES

  1. Miranda-Filho A, Pineros M, Ferlay J, et al. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol. 2018;5(1):e14–e24. doi: 10.1016/S2352-3026(17)30232-6.
  2. The global burden of haematological diseases. Lancet Haematol. 2020;7(12):e851. doi: 10.1016/S2352-3026(20)30370-7.
  3. Igissinov N, Kulmirzayeva D, Moore MA, et al. Epidemiological Assessment of Leukemia in Kazakhstan, 2003–2012. Asian Pac J Cancer Prev. 2014;15(16):6969–72. doi: 10.7314/apjcp.2014.15.16.6969.
  4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30. doi: 10.3322/caac.21387.
  5. Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392(10147):593–606. doi: 10.1016/S0140-6736(18)31041-9.
  6. Dong Y, Shi O, Zeng Q, et al. Leukemia incidence trends at the global, regional, and national level between 1990 and 2017. Exp Hematol Oncol. 2020;9:14. doi: 10.1186/s40164-020-00170-6.
  7. Meillon-Garcia LA, Demichelis-Gomez R. Access to Therapy for Acute Myeloid Leukemia in the Developing World: Barriers and Solutions. Curr Oncol Rep. 2020;22(12):125. doi: 10.1007/s11912-020-00987-8.
  8. Колеснев А.В., Клодзинский А.А., Гайнутдинова О.В. и др. Острый миелобластный лейкоз у взрослых: первые результаты лечения по протоколу AML 2012/203KZ/VII. Международный симпозиум, посвященный памяти Раисы Максимовны Горбачевой «Трансплантация гемопоэтических стволовых клеток у детей и взрослых», 19–21 сентября 2013 г. Астана, Республика Казахстан.
    [Kolesnev AV, Klodzinskii AA, Gainutdinova OV, et al. Acute myeloblastic leukemia in adults: first outcomes of treatment according to AML 2012/203KZ/VII regimen. International symposium in memory of Raisa Maksimovna Gorbacheva “Hematopoietic Stem Cell Transplantation in Children and Adults”. Astana; September 19–21, 2013. (In Russ)]
  9. Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47. doi: 10.1182/blood-2016-08-733196.
  10. Тургунова Л.Г., Шилова В.Н., Недова О.И. и др. Результаты лечения острых лейкозов у взрослых. Астана медициналык журналы. 2005;3:94–6.
    [Turgunova LG, Shilova VN, Nedova OI, et al. Outcomes of acute leukemia treatment in adults. Astana meditsinalyk zhurnaly. 2005;3:94–6. (In Russ)]
  11. Jacob S, Jacob SE, Suryanarayana BS, et al. Clinical Profile and Short Term Outcome of Adult Patients with Acute Myeloid Leukemia. Indian J Hematol Blood Transfus. 2019;5(3):431–6. doi: 10.1007/s12288-018-1051-9.
  12. Noone AM, Howlader N, Krapcho M, et al. SEER cancer statistics review, 1975–2015. Bethesda: National Cancer Institute; 2018.
  13. Colunga-Pedraza PR, Gomez-Cruz GB, Colunga-Pedraza JE, Ruiz-Arguelles GJ. Geographic hematology: some observations in Mexico. Acta Haematol. 2018;140(2):114–20. doi: 10.1159/000491989.
  14. Gomez-Almaguer D, Marcos-Ramirez ER, Montano-Figueroa EH, et al. Acute leukaemia characteristics are different around the world: the Mexican perspective. Clin Lymphoma Myeloma Leuk. 2017;17(1):46–51. doi: 10.1016/j.clml.2016.09.003.
  15. Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program. 2016;2016(1):339–47. doi: 10.1182/asheducation-2016.1.339.
  16. Kayal S, Sengar M, Jain H, et al. Induction Related Mortality in Acute Myeloid Leukemia: Multivariate Model of Predictive Score from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC). Blood. 2019;134(Suppl_1):2615. doi: 10.1182/blood-2019-127623.
  17. Othus M, Kantarjian H, Petersdorf S, et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. Leukemia. 2014;28(2):289–92. doi: 10.1038/leu.2013.176.
  18. Ho G, Jonas BA, Li Q, et al. Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia. Br J Haematol. 2017;177(5):791–9. doi: 10.1111/bjh.14631.
  19. Demichelis R, Zapata N, Leyto F, et al. Survival analysis of adult patients with acute myeloid leukemia (AML) treated with intensive chemotherapy: results of a Mexican national AML registry. Clin Lymphoma Myeloma Leuk. 2019;19(1):S209–S2010. doi: 10.1016/j.clml.2019.07.074.
  20. Benicio MTL, Ribeiro AFT, Americo AD, et al. Evaluation of the European LeukemiaNet recommendations for predicting outcomes of patients with acute myeloid leukemia treated in low- and middle-income countries (LMIC): a Brazilian experience. Leuk Res. 2017;60:109–14. doi: 10.1016/j.leukres.2017.07.005.
  21. Malkan UY, Gunes G, Eliacik E. The factors affecting early death after the initial therapy of acute myeloid leukemia. Int J Clin Exp Med. 2015;8(12):22564–9.
  22. Reville PK, Gonzalez GMN, Ravandi F, et al. Predictors of Early Mortality, Response, and Survival in Newly Diagnosed Acute Myeloid Leukemia (AML) Using a Contemporary Academic Cohort. Blood. 2020;136(Suppl 1):44–5. doi: 10.1182/blood-2020-141837.
  23. Master S, Mansour R, Devarakondaet SS, et al. Predictors of Survival in Acute Myeloid Leukemia by Treatment Modality. Anticancer Res. 2016;36(4):1719–27.
  24. Schuurhuis GJ, Heuser M, Freeman S, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131(12):1275–91. doi: 10.1182/blood-2017-09-801498.
  25. Philip C, George B, Ganapule A, et al. Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol. 2015;170(1):110–7. doi: 10.1111/bjh.13406.
  26. Loke J, Malladi R, Moss P, et al. The role of allogeneic stem cell transplantation in the management of acute myeloid leukaemia: a triumph of hope and experience. Br J Haematol. 2020;188(1):129–46. doi: 10.1111/bjh.16355.

The Role of BAALC-Expressing Leukemia Precursor Cells in the Pathogenesis of Myelodysplastic Syndromes

AUTOIMMUNE THROMBOCYTOPENIA , ,

NN Mamaev, MV Latypova, AI Shakirova, TL Gindina, MM Kanunnikov, NYu Tsvetkov, IM Barkhatov, SN Bondarenko, MD Vladovskaya, EV Morozova

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

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

For citation: Mamaev NN, Latypova MV, Shakirova AI, et al. The Role of BAALC-Expressing Leukemia Precursor Cells in the Pathogenesis of Myelodysplastic Syndromes. Clinical oncohematology. 2022;15(1):62–8. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-62-68

ABSTRACT

The present paper provides evidence for a high detection rate of BAALC gene overexpression, also combined with WT1 gene overexpression, in patients with myelodysplastic syndromes (MDS) and FISH-verified chromosome defects. The BAALC and WT1 gene expression profiling in 16 MDS patients (6 out of them received allogeneic hematopoietic stem cell transplantation) showed an increased BAALC expression in 14 patients. The expression level in 2 patients was near the cut-off. Low expression levels were identified in a female patient with isolated 5q deletion in karyotype and also with its combination with complex karyotype. On the other hand, the highest expression levels were reported in patients with normal karyotype and 3q26 locus rearrangement, which was associated with EVI1 gene overexpression. Since the BAALC expression level, at least in patients with the major (except for М3 and М7) FAB-variants of acute myeloid leukemias (AML), was closely associated with BAALC-producing precursor cells of leukemia clone, a profound study of this phenomenon in MDS patients seems to be important for understanding the finest mechanisms underlying the pathogenesis of AML and AML relapses on the level of precursor cells.

Keywords: myelodysplastic syndromes, BAALC and WT1 genes, overexpression, post-transplantation relapses, BAALC-producing precursor cells, pathogenesis, prognosis.

Received: July 7, 2021

Accepted: November 4, 2021

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REFERENCES

  1. Gadji M, Pozzo AR. From cellular morphology to molecular and epigenetic anomalies of myelodysplastic syndromes. Genes Chromos Cancer. 2019;58(7):474–83. doi: 10.1002/gcc.22689.
  2. Schanz J, Cevik N, Fonatsch C, et al. Detailed analysis of clonal evolution and cytogenetic evolution patterns in patients with myelodysplastic syndromes (MDS) and related myeloid disorders. Blood Cancer J. 2018;8(3):28. doi: 10.1038/s41408-018-0061-z.
  3. Bersanelli M, Travaglino E, Meggendorfer M, et al. Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes. J Clin Oncol. 2021;39(11):1223–33. doi: 10.1200/JCO.20.01659.
  4. Papaemmanuil E, Gerstung M, Malcovati L, et al. Сlinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27. doi: 10.1182/blood-2013-08-518886.
  5. Minetto P, Guolo F, Cavio M, et al. Combined assessment of WT1 and BAALC gene expression at diagnosis may improve leukemia-free survival prediction in patients with myelodysplastic syndromes. Leuk Res. 2015;39(8):866–73. doi: 10.1016/leukres.2015/04/011.
  6. Мамаев Н.Н., Шакирова А.И., Бархатов И.М. и др. Ведущая роль BAALC-экспрессирующих клеток-предшественниц в возникновении и развитии посттрансплантационных рецидивов у больных острыми миелоидными лейкозами. Клиническая онкогематология. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88.
    [Mamaev NN, Shakirova AI, Barkhatov IM, et al. Crucial Role of BAALC–Expressing Progenitor Cells in Emergence and Development of Post-Transplantation Relapses in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88. (In Russ)]
  7. Mamaev NN, Shakirova AI, Barkhatov IM, et al. Crucial role of BAALC-expressing leukemic precursors in origin and development of posttransplant relapses in patients with acute myeloid leukemias. Int J Hematol. 2020;8(6):127–31. doi: 10.15406/htij.2020.08.00240.
  8. Mamaev NN, Shakirova AI, Barkhatov IM, et al. New opportunities for assay of leukemia initiating cells (LICs) participating in post-transplant relapse development in the patients with acute myeloid leukemia. 3rd Annual IACH Meeting, 1–3 October, 2020, Paris. Report #12.
  9. Mamaev NN, Shakirova AI, Gindina TL, et al. Quantitative study of BAALC- and WT1-expressing cell precursors in the patients with different cytogenetic and molecular AML variants treated with Gemtuzumab ozogamicin and hematopoietic stem cell transplantation. Cell Ther Transplant. 2021;10(1):55–62. doi: 10.18620/ctt-1866-8836-2021-10-1-55-62.
  10. Thol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood. 2012;119(15):3578–84. doi: 10.1182/blood-2011-12-399337.
  11. Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodyspl astic sendromes. Leukemia. 2014;18(2):241–7. doi: 10.1038/leu.2013.336.
  12. Pauebelle E, Piesa A, Hayette S, et al. Efficacy of all-trans-retinoic acid in high risk acute myeloid leukemia with overexpression of EVI1. Oncol Ther. 2019;7(2):121–30. doi: 10.1007/s40487-019-0095-9.
  13. Field T, Perkins KJ, Huang Y, et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010;45(2):255–60. doi: 10.1038/bmt.2009.134.
  14. Мамаев Н.Н., Шакирова А.И., Морозова Е.В., Гиндина Т.Л. EVI1-позитивные лейкозы и миелодиспластические синдромы: теоретические и клинические аспекты (обзор литературы). Клиническая онкогематология. 2021;14(1):103–17. doi: 10.21320/2500-2139-2021-14-1-103-117.
    [Mamaev NN, Shakirova AI, Morozova EV, Gindina TL. EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2021;14(1):103–17. doi: 10.21320/2500-2139-2021-14-1-103-117. (In Russ)]
  15. Geoffroy М-С, Esnault C, de The H. Retinoids in hematology: a timely revival? Blood. 2021;137(18):2429–37. doi: 10.1182/blood.2020010100.

Russian Prospective Non-Randomized Clinical Study on Dose Reduction of Tyrosine Kinase Inhibitors with Subsequent Complete Therapy Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response (READIT-2020): Background, Aim, Main Objectives, Design, and Expected Results

AUTOIMMUNE THROMBOCYTOPENIA ,

AG Turkina, MA Gurianova, EYu Chelysheva, OA Shukhov

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

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

For citation: Turkina AG, Gurianova MA, Chelysheva EYu, Shukhov OA. Russian Prospective Non-Randomized Clinical Study on Dose Reduction of Tyrosine Kinase Inhibitors with Subsequent Complete Therapy Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response (READIT-2020): Background, Aim, Main Objectives, Design, and Expected Results. Clinical oncohematology. 2022;15(1):54–61. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-54-61

ABSTRACT

Background. A withdrawal of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients with optimal response, especially in patients with drug toxicity, is a matter of current interest. According to the results of numerous clinical studies, the probability of sustaining treatment-free remission (TFR) in CML patients with deep molecular response (DMR) is about 40–60 %. Great attention has recently been paid to personalized therapy consisting in TKI dose modification aimed at reducing or preventing therapy adverse events. Many large retrospective studies showed that reduced TKI doses in CML patients with major molecular response (MMR) and DMR is a safe therapy option. The follow-up of patients receiving reduced TKI doses is also carried out under prospective clinical studies as a stage prior to therapy discontinuation. This approach shows that the probability of sustaining TFR after the stage of TKI dose reduction is about 70 % which is higher than that after the withdrawal of standard TKI doses.

Aim. To present the background, aim, and main objectives of the study as well as the design and expected results.

Materials & Methods. READIT-2020 (Russian prospective study of REduction And DIscontinuation Treatment of TKI) is a Russian prospective non-randomized clinical study with the main aim of developing a safe management regimen for CML patients with MMR and DMR, who receive reduced TKI doses, with subsequent follow-up in the period of TFR under the control of minimal residual disease. The study is going to enroll 100 patients. Each stage of the clinical study will include a regular molecular genetic monitoring at the central laboratory (National Research Center for Hematology, Moscow). The primary objective is to assess survival without MMR loss (BCR-ABL > 0.1 %) both on reduced TKI doses and during TFR. The primary endpoint is the follow-up period of 12 months after TKI discontinuation.

Trial Registration No.: NCT04578847 (Clinicaltrial.gov).

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

Received: June 2, 2021

Accepted: November 1, 2021

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REFERENCES

  1. Bower H, Bjorkholm M, Dickman PV, et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–7. doi: 10.1200/JCO.2015.66.2866.
  2. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–27. doi: 10.1056/NEJMoa1609324.
  3. Шухов О.А. Молекулярно-цитогенетическая характеристика Ph-позитивного клона у больных хроническим миелолейкозом при длительном воздействии ингибиторов тирозинкиназ: Дис. … канд. мед. наук. М., 2015. 114 с.
    [Shukhov OA. Molekulyarno-tsitogeneticheskaya kharakteristika Ph-pozitivnogo klona u bol’nykh khronicheskim mieloleikozom pri dlitel’nom vozdeistvii ingibitorov tirozinkinaz. (Molecular and cytogenetic characteristics of the Ph-positive clone in patients with chronic myeloid leukemia with prolonged exposure to tyrosine kinase inhibitors.) [dissertation] Moscow; 2015. 114 p. (In Russ)]
  4. Туркина А.Г., Челышева Е.Ю. Стратегия терапии хронического миелоидного лейкоза: возможности и перспективы. Терапевтический архив. 2013;85(7):4–9.
    [Turkina AG, Chelysheva EYu. Therapeutic strategy for chronic myeloid leukemia: possibilities and prospects. Terapevticheskii arkhiv. 2013;85(7):4–9. (In Russ)]
  5. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747–57. doi: 10.1016/S1470-2045(18)30192-X.
  6. Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French Stop Imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2017;35(3):298–305. doi: 10.1200/jco.2016.68.2914.
  7. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846–54. doi: 10.1182/blood-2016-09-742205.
  8. Hughes T, Boquimpani C, Takahashi N, et al. Durable treatment free remission after stopping second-line nilotinib in patients with chronic myeloid leukemia in chronic phase: ENESTOP 96-wk update. Haematologica. 2017;102(S2):75.
  9. Туркина А.Г., Петрова А.Н., Челышева Е.Ю. и др. Результаты проспективного исследования по наблюдению больных хроническим миелолейкозом после прекращения терапии ингибиторами тирозинкиназ. Гематология и трансфузиология. 2020;65(4):370–85. doi: 10.35754/0234-5730-2020-65-4-370-385.
    [Turkina AG, Petrova AN, Chelysheva EYu, et al. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian journal of hematology and transfusiology. 2020;65(4):370–85. doi: 10.35754/0234-5730-2020-65-4-370-385. (In Russ)]
  10. Ломаиа Е.Г., Романова Е.Г., Сбитякова Е.И., Зарицкий А.Ю. Эффективность и безопасность ингибиторов тирозинкиназ 2-го поколения (дазатиниб, нилотиниб) в терапии хронической фазы хронического миелолейкоза. Онкогематология. 2013;2:22–33.
    [Lomaia EG, Romanova EG, Sbityakova EI, Zaritskiy AYu. Efficacy and safety of tyrosine kinase inhibitors (dasatinib, nilotinib) in the treatment of chronic phase chronic myeloid leukemia. 2013;2:22–33. (In Russ)]
  11. Лазорко Н.С., Ломаиа Е.Г., Романова Е.Г. и др. Ингибиторы тирозинкиназ второго поколения и их токсичность у больных в хронической фазе хронического миелолейкоза. Клиническая онкогематология. 2015;8(3):302–8. doi: 10.21320/2500-2139-2015-8-3-302-308.
    [Lazorko NS, Lomaia EG, Romanova EG, et al. Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia. Clinical oncohematology. 2015;8(3):302–8. doi: 10.21320/2500-2139-2015-8-3-302-308. (In Russ)]
  12. Гурьянова М.А., Челышева Е.Ю., Туркина А.Г. Возможности терапии ингибиторами тирозинкиназ в сниженных дозах у пациентов с хроническим миелолейкозом. Клиническая онкогематология. 2021;14(1):118–28. doi: 10.21320/2500-2139-2021-14-1-118-128.
    [Gurianova MA, Chelysheva EYu, Turkina AG. Opportunities of Chronic Myeloid Leukemia Treatment with Reduced Doses of Tyrosine Kinase Inhibitors. Clinical oncohematology. 2021;14(1):118–28. doi: 10.21320/2500-2139-2021-14-1-118-128. (In Russ)]
  13. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531–41. doi: 10.1056/NEJMoa055229.
  14. Santana-Hernandez P, Pedraza RCP, Duque SG, et al. Low-Dose Dasatinib as First-Line Treatment for Chronic Myeloid Leukemia: Preliminary Blood. 2017;130(Suppl 1):5254. doi: 10.1182/blood.V130.Suppl_1.5254.5254.
  15. Naqvi K, Jabbour E, Skinner J, et al. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2020;126(1):67–75. doi: 10.1002/cncr.32504.
  16. Cervantes F, Correa J-G, Perez I, et al. Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response. Ann Hematol. 2017;96(1):81–5. doi: 10.1007/s00277-016-2839-z.
  17. Iriyama N, Ohashi K, Hashino S, et al. The efficacy of reduced-dose dasatinib as a subsequent therapy in patients with chronic myeloid leukemia in the chronic phase: the LD-CML study of the Kanto CML Study Group. Intern Med. 2018;57(1):17–23. doi: 10.2169/internalmedicine.9035-17.
  18. Faber E, Divoka M, Skoumalova I, et al. A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment. Leuk Lymphoma. 2016;57(2):370–5. doi: 3109/10428194.2015.1056184.
  19. Шухов О.А., Гурьянова М.А., Челышева Е.Ю. и др. Оценка стабильности молекулярного ответа у больных хроническим миелоидным лейкозом на сниженных дозах ингибиторов тирозинкиназ второго поколения. Гематология и трансфузиология. 2020;65(1, прил. 1):111–2.
    [Shukhov OA, Gurianova MA, Chelysheva EYu, et al. Assessment of the molecular response stability in patients with chronic myeloid leukemia on reduced doses of second-generation tyrosine kinase inhibitors. Gematologiya i transfuziologiya. 2020;65(1 Suppl 1):111–2. (In Russ)]
  20. Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 2017;4(7):e310–e316. doi: 10.1016/s2352-3026(17)30066-
  21. Rea D, Cayuela J-M, Dulucq S, et al. Molecular responses after switching from a standard-dose twice-daily nilotinib regimen to a reduced-dose once-daily schedule in patients with chronic myeloid leukemia: a real life observational study (NILO-RED). 2017;130(Suppl 1):318. doi: 10.1182/blood.V130.Suppl_1.318.318.
  22. Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019;6(7):e375–e383. doi: 10.1016/S2352-3026(19)30094-8.
  23. Claudiani S, Apperley J, Khan A, et al. Dose reduction of first and second generation TKIs is effective in the maintenance of major molecular response and may predict successful Tfr in CML patients. 2018;132(Suppl 1):3007. doi: 10.1182/blood-2018-99-119602.
  24. Cayssials E, Torregrosa‐Diaz J, Gallego‐Hernanz P, et al. Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: results of a retrospective study. Cancer. 2020;126(15):3438–47. doi: 10.1002/cncr.32940.
  25. Kim DDH, Busque L, Forrest DL, et al. Second attempt of TKI discontinuation with dasatinib for treatment-free remission after failing first attempt with imatinib: treatment-free remission accomplished by dasatinib (TRAD) trial. 2018;132(Suppl 1):787. doi: 10.1182/blood-2018-99-114656.
  26. Legros L, Nicolini F-Е, Etienne G, et al. The TKI-Free Duration after a First Discontinuation Attempt That Failed in CP CML Patients Is a Predictive Factor of TKI-Free Remission after a Second Attempt. 2019;134(Suppl 1):28. doi: 10.1182/blood-2019-123719.
  27. Шуваев В.А., Абдулкадыров К.М., Мартынкевич И.С., Фоминых М.С. Фармакоэкономическое моделирование таргетной терапии у больных хроническим миелолейкозом в ремиссии. Онкогематология. 2014;9(3):16–24. doi: 17650/1818-8346-2014-9-3-16-24.
    [Shuvaev VA, Abdulkadyrov KM, Martynkevich IS, Fominykh MS. Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission. Oncohematology. 2014;9(3):16–24. doi: 10.17650/1818-8346-2014-9-3-16-24. (In Russ)]

The Efficacy of Brentuximab Vedotin in Relapsed/Refractory Classical Hodgkin’s Lymphoma and Quality of Life: Results of a Multi-Center Observational Prospective Study in the Context of Real Clinical Practice

AUTOIMMUNE THROMBOCYTOPENIA , ,

TI Ionova1,2, AA Amdiev3, MI Andrievskikh4, EA Baryakh5, EV Vasilev6, MV Volkov7, EM Volodicheva8, VV Ivanov9, OV Kaverina10, KD Kaplanov11, TYu Klitochenko12, VI Kurakin13, DG Lazareva10, OG Larionova7, KV Lepik14, IB Lysenko15, VYa Melnichenko16, RI Minullina17, OV Mironov18, EN Misyurina5, NB Mikhailova14, NE Mochkin16, TP Nikitina1,2, TS Petrova17, NM Porfireva1, OA Rukavitsyn19, AA Samoilova16, RN Safin17, PI Simashova19, EG Smirnova16, NA Trenina13, NV Fadeeva4, GN Khusainova17, VL Chang18, TV Shelekhova20, DG Sherstnev20

1 Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014

2 NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 154 Fontanki emb., Saint Petersburg, Russian Federation, 198103

3 VM Efetov Crimea Republican Clinical Oncology Dispensary, 49A Bespalova str., Simferopol, Russian Federation, 295007

4 Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087

5 Municipal Clinical Hospital No. 52, 5 Marshala Katukova str., Moscow, Russian Federation, 123181

6 Krasnoyarsk Krai Clinical Hospital, 3A Partizana Zheleznyaka str., Krasnoyarsk, Russian Federation, 660022

7 Primorsky Krai Oncology Dispensary, 59 Russkaya str., Vladivistok, Russian Federation, 690105

8 Tula Regional Clinical Hospital, 1A bld. 1 Yablochkova str., Tula, Russian Federation, 300053

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

10 Altai Krai Oncology Dispensary, 110 Zmeinogorskii passage, Barnaul, Russian Federation, 656045

11 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

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

13 Clinical Oncology Dispensary, 9 bld. 1 Zavertyaeva str., Omsk, Russian Federation, 644013

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

15 National Medical Cancer Research Center, 63 bld. 8 14th line str., Rostov-on-Don, Russian Federation, 344037

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

17 Tatarstan Republican Clinical Oncology Dispensary, 29 bld. A Sibirskii passage, Kazan, Russian Federation, 420029

18 Tambov Regional Clinical Oncology Dispensary, 29B Moskovskaya str., Tambov, Russian Federation, 392000

19 NN Burdenko Central Military Clinical Hospital, 3 Gospital’naya sq., Moscow, Russian Federation, 105229

20 VI Razumovskii Saratov State Medical University, 6/9 53rd Strelkovoi Divizii str., Saratov, Russian Federation, 410028

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014; e-mail: qolife@mail.ru

For citation: Ionova TI, Amdiev AA, Andrievskikh MI, et al. The Efficacy of Brentuximab Vedotin in Relapsed/Refractory Classical Hodgkin’s Lymphoma and Quality of Life: Results of a Multi-Center Observational Prospective Study in the Context of Real Clinical Practice. Clinical oncohematology. 2022;15(1):42–53. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-42-53

ABSTRACT

Aim. To study the quality of life and symptoms, to assess the clinical effect and treatment safety in relapsed/refractory classical Hodgkin’s lymphoma (r/r cHL) patients treated with brentuximab vedotin (BV) as ≥ 3rd-line therapy in the context of real clinical practice.

Materials & Methods. The study enrolled 62 r/r cHL patients after the second- and subsequent-line chemotherapies, who are either ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) at the time of their enrollment into the study or after the failure of high-dose chemotherapy (HDCT) with auto-HSCT. The median age was 31 years; 46.8 % of patients were women. The patients received BV 1.8 mg/kg intravenously every 3 weeks. Clinical parameters, quality of life, and symptoms were assessed prior to BV therapy and in 3, 6, 9, 12, and 15 months after therapy onset. The RAND SF-36 form was used to assess the quality of life, and the ESAS-R tool was applied to report on symptoms.

Results. Objective response was observed in 68.3 % of patients, 40 % out of them showed complete response. The median progression-free survival was 10.6 months (95% confidence interval 7.4–12.9 months). Safety profile corresponded to the published data. Adverse events of grade 3/4 were identified in 1.6 % of patients. In the period of 15 months after therapy onset, quality of life improvement or stabilization was reported based on all the scales of RAND SF-36 (GEE, p < 0.001), and symptom abatement was proved based on ESAS-R total score (GEE, p < 0.001).

Conclusion. In the context of real clinical practice, BV appeared to be effective in r/r cHL patients either after the second- or subsequent-line chemotherapies or after the failure of HDCT with auto-HSCT. The study demonstrated that BV was well tolerated by the patients. BV therapy contributes to the improvement of r/r cHL patients’ quality of life. Positive changes in quality of life and symptoms on BV therapy testify to its patient-assessed efficacy.

Keywords: classical Hodgkin’s lymphoma, relapsed/refractory form, brentuximab vedotin, quality of life, real clinical practice.

Received: June 29, 2021

Accepted: November 19, 2021

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REFERENCES

  1. Демина Е.А. Руководство по лечению лимфомы Ходжкина. М.: Ремедиум, 2018. 72 с.
    [Demina EA. Rukovodstvo po lecheniyu limfomy Khodzhkina. (Guidelines for the treatment of Hodgkin’s lymphoma.) Moscow: Remedium Publ.; 2018. 72 p. (In Russ)]
  2. Engert A, Younes A. Hematologic malignancies: Hodgkin lymphoma (2nd ed.). A Comprehensive Update on Diagnostics and Clinics. Berlin Heidelberg: Springer; 2015. 437 p. doi: 10.1007/978-3-319-12505-3.
  3. Canellos G, Anderson J, Propert K, et al. Chemotherapy of Advanced Hodgkin’s Disease with MOPP, ABVD, or MOPP Alternating with ABVD. N Engl J Med. 1992;327(21):1478–84. doi: 10.1056/nejm199211193272102.
  4. Rancea M, Monsef I, von Tresckow B, et al. High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev. 2013;(6):CD009411. doi: 10.1002/14651858.CD009411.pub2.
  5. Демина Е.А. Брентуксимаб ведотин: новые возможности лечения рецидивов и рефрактерных форм лимфомы Ходжкина. Клиническая онкогематология. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405.
    [Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405. (In Russ)]
  6. Yi J, Kim S, Kim W. Brentuximab vedotin: clinical updates and practical guidance. Blood Res. 2017;52(4):243–53. doi: 10.5045/br.2017.52.4.243.
  7. Gravanis I, Tzogani K, Hennik P, et al. The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. 2015;21(1):102–9. doi: 10.1634/theoncologist.2015-0276.
  8. Younes A, Bartlett N, Leonard J, et al. Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas. N Engl J Med. 2010;363(19):1812–21. doi: 10.1056/nejmoa1002965.
  9. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183–9. doi: 10.1200/JCO.2011.38.0410.
  10. Forero‐Torres A, Fanale M, Advani R, et al. Brentuximab Vedotin in Transplant‐Naive Patients with Relapsed or Refractory Hodgkin Lymphoma: Analysis of Two Phase I Studies. Oncologist. 2012;17(8):1073–80. doi: 10.1634/theoncologist.2012-0133.
  11. Chen R, Gopal A, Smith S, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. 2016;128(12):1562–6. doi: 10.1182/blood-2016-02-699850.
  12. Zinzani P, Corradini P, Gianni A, et al. Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. Clin Lymphoma Myeloma Leuk. 2015;15(9):507–13. doi: 10.1016/j.clml.2015.06.008.
  13. Rothe A, Sasse S, Goergen H, et al. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. 2012;120(7):1470–2. doi: 10.1182/blood-2012-05-430918.
  14. Gibb A, Jones C, Bloor A, et al. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. 2012;98(4):611–4. doi: 10.3324/haematol.2012.069393.
  15. Perrot A, Monjanel H, Bouabdallah R, et al. Brentuximab vedotin as single agent in refractory or relapsed CD30-positive Hodgkin lymphoma: the French name patient program experience in 241 patients. 2014;99(1):498.
  16. Zinzani P, Viviani S, Anastasia A, et al. Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials. 2013;98(8):1232–6. doi: 10.3324/haematol.2012.083048.
  17. Linendoll N, Saunders T, Burns R, et al. Health-related quality of life in Hodgkin lymphoma: a systematic review. Health Qual Life Outcomes. 2016;14(1):114. doi: 10.1186/s12955-016-0515-6.
  18. Kreissl S, Muller H, Goergen H, et al. Health-Related Quality of Life in Patients With Hodgkin Lymphoma: A Longitudinal Analysis of the German Hodgkin Study Group. J Clin Oncol. 2020;38(25):2839–48. doi: 10.1200/jco.19.03160.
  19. Parsons S. Longitudinal Assessment of Health-Related Quality of Life Among Survivors of Hodgkin Lymphoma: It Is About Time! J Clin Oncol. 2020;38(25):2821–3. doi: 10.1200/jco.20.01585.
  20. Pophali P, Larson M, Rosenthal A, et al. The association of health behaviors with quality of life in lymphoma survivors. Leuk Lymphoma. 2020;62(2):271–80. doi: 10.1080/10428194.2020.1830389.
  21. Novik A, Salek S, Ionova T. Guidelines. Patient-reported outcomes in. Genoa: Forum service editore, 2012. Available from: https://ehaweb.org/assets/Uploads/EHA-Guideline-libro.pdf (accessed 24.06.2021).
  22. Chen R, Bartlett N, Brice P, et al. Patient-reported outcomes of brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma. Onco Targets Ther. 2016;9:2027–34. doi: 10.2147/ott.s96175.
  23. Ramsey S, Nademanee A, Masszi T, et al. Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma. Br J Haematol. 2016;175(5):860–7. doi: 10.1111/bjh.14316.
  24. Parker C, Woods B, Eaton J, et al. Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous stem cell transplant: a cost-effectiveness analysis in Scotland. J Med Econ. 2016;20(1):8–18. doi: 10.1080/13696998.2016.1219358.
  25. Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. doi: 10.1016/j.ejca.2008.10.026.
  26. Moghbel M, Kostakoglu L, Zukotynski K, et al. Response Assessment Criteria and Their Applications in Lymphoma: Part 1. J Nucl Med. 2016;57(6):928–35. doi: 10.2967/jnumed.115.166280.
  27. Common Terminology Criteria for Adverse Evens (CTCAE 4) Version 4.0. Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5х11.pdf (accessed 24.06.2021).
  28. Charlson M, Pompei P, Ales K, MacKenzie C. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8.
  29. Hays RD, Sherbourne CD, Mazel RM. User’s Manual for Medical Outcomes Study (MOS) Core measures of health-related quality of life. RAND Corporation, 1995. Available from: www.rand.org (accessed 24.06.2021).
  30. Mols F, Aaronson N, Vingerhoets A, et al. Quality of life among long-term non-Hodgkin lymphoma survivors. 2007;109(8):1659–67. doi: 10.1002/cncr.22581.
  31. Новик А.А., Ионова Т.И., Гандек Б. и др. Показатели качества жизни населения Санкт-Петербурга. Проблемы стандартизации в здравоохранении. 2003;8:14–26.
    [Novik AA, Ionova TI, Gandek B, et al. Quality of life indicators for Saint Petersburg citizens. Problemy standartizatsii v zdravookhranenii. 2003;8:14–26. (In Russ)]
  32. Bruera E, Kuehn N, Miller M, et al. The Edmonton Symptom Assessment System (ESAS): A Simple Method for the Assessment of Palliative Care Patients. J Palliat Care. 1991;7(2):6–9. doi: 10.1177/082585979100700202.
  33. Chen R, Gopal AK, Smith SE, et al. Five-Year Survival Data Demonstrating Durable Responses From a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma. Clin Adv Hematol Oncol. 2016;4(2 Suppl 1):6.
  34. Gopal A, Chen R, Smith S, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. 2015;125(8):1236–43. doi: 10.1182/blood-2014-08-595801.
  35. Kuruvilla J, Ramchandren R, Santoro A, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22(4):512–24. doi: 10.1016/s1470-2045(21)00005-x.
  36. Gandolfi L, Pellegrini C, Casadei B, et al. Long‐Term Responders After Brentuximab Vedotin: Single‐Center Experience on Relapsed and Refractory Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma Patients. 2016;21(12):1436–41. doi: 10.1634/theoncologist.2016-0112.
  37. Donato E, Fernandez-Zarzoso M, Hueso J, de la Rubia J. Brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma: an evidence-based review. Onco Targets Ther. 2018;11:4583–90. doi: 10.2147/ott.s141053.

Plasmablastic Lymphoma in HIV-Positive Patients: A Literature Review and Results of a Russian Multi-Center Retrospective Study

AUTOIMMUNE THROMBOCYTOPENIA , ,

MO Popova1, IV Tsygankov1, YaV Gudozhnikova1, YuA Rogacheva1, NP Volkov1, KV Lepik1, MV Demchenkova2, MV Grigoreva2, AYu Efirkina2, TV Shneider3, YuV Kopeikina3, SA Stepanova3, VG Potapenko4, AV Klimovich4, NV Medvedeva4, MA Kolesnikova5, TI Pospelova5, NB Mikhailova1, VV Baikov1, AD Kulagin1

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

2 Irkutsk Regional Cancer Center, 32 Frunze str., Irkutsk, Russian Federation, 664035

3 Leningrad Regional Clinical Hospital, 45 bld. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

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

5 Municipal Center for Hematology, 21 Polzunova str., Novosibirsk, Russian Federation, 630051

For correspondence: Marina Olegovna Popova, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(911)711-39-77; e-mail: marina.popova.spb@gmail.com

For citation: Popova MO, Tsygankov IV, Gudozhnikova YaV, et al. Plasmablastic Lymphoma in HIV-Positive Patients: A Literature Review and Results of a Russian Multi-Center Retrospective Study. Clinical oncohematology. 2022;15(1):28–41. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-28-41

ABSTRACT

Background. Plasmablastic lymphoma (PBL) is a rare lymphoproliferative disease which is almost exclusively associated with immunodeficiency. Most ample experience of chemotherapy and hematopoietic stem cells transplantation (HSCT) in this lymphoma variant has been accumulated in HIV-positive patients.

Aim. To describe the current approaches to PBL diagnosis and treatment in HIV-positive patients as well as to provide the results of the first multi-center retrospective study on PBL epidemiology and therapy efficacy in HIV-positive patients in the Russian Federation.

Materials & Methods. The study included 26 HIV-positive patients with PBL who were treated and followed-up at 5 Russian centers during 2012–2019. The present study is a part of multi-center retrospective study on lymphoma epidemiology in HIV-positive patients in Russia.

Results. PBL accounted for 9.5 % of all lymphomas in HIV-positive patients enrolled in multi-center retrospective study on lymphoma epidemiology in HIV-positive patients in Russia. Epidemiological characteristics of these patients corresponded to those described in previously published literature: the disease being diagnosed mainly at late stages (88 %), oral and nasal mucosa lesions with a common involvement of facial bones (65 %), and lack of optimal HIV-infection control (66.7 %). Most commonly, the patients received EPOCH-like treatment as first-line therapy (50 %). However, the efficacy of primary therapy appeared to be low. Overall survival (OS) and progression-free survival (PFS) during a year after first-line therapy onset was 57 % and 46 %, respectively. Bortezomib included in first-line therapy was associated with a trend to a more favorable prognosis. Half of patients showed a lymphoma relapse or progression after first-line therapy. Most used second-line regimen was DHAP. Overall response to second-line therapy was 38.5 %. After second-line therapy onset, 1-year OS and PFS were 26 % and 15 %, respectively.

Conclusion. HIV-positive patients with PBL have poor prognosis. Efforts to improve the prognosis for HIV-positive patients with PBL should be aimed at increasing the efficacy of first-line therapy and should involve the use of intensive chemotherapy regimens with bortezomib. The role of auto- and allo-HSCTs in the treatment of PBL has not been clearly determined, however, PBL patients, despite their HIV-infection, should be regarded as auto-HSCT-eligible in the first remission and allo-HSCT-eligible in case of relapse. Further prospective multi-center studies are needed to optimize the treatment of HIV-positive patients with PBL.

Keywords: plasmablastic lymphoma, HIV-infection, Epstein-Barr virus, MYC, PD-1/PD-L1/2, auto-HSCT, allo-HSCT, bortezomib, nivolumab, immunotherapy.

Received: July 20, 2021

Accepted: November 27, 2021

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REFERENCES

  1. World Health Organization. HIV data and statistics. Available from: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics (accessed 20.07.2021).
  2. Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103(9):753–62. doi: 10.1093/jnci/djr076.
  3. Heron M. Deaths: Leading Causes for 2017. Natl Vital Stat Rep. 2019;68(6):1–77.
  4. Selik RM, Mokotoff ED, Branson B, et al. Revised Surveillance Case Definition for HIV Infection — United States, 2014. Morbid Mortal Weekly Rep. 2014;63(RR-03):1–10.
  5. Robbins HA, Shiels MS, Pfeiffer RM, et al. Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States. AIDS. 2014;28(6):881–90. doi: 10.1097/QAD.0000000000000163.
  6. Goncalves PH, Montezuma-Rusca JM, Yarchoan R, Uldrick TS. Cancer prevention in HIV-infected populations. Semin Oncol. 2016;43(1):173–88. doi: 10.1053/j.seminoncol.2015.09.011.
  7. Delecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. 1997;89(4):1413–20.
  8. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32. doi: 10.1182/blood-2011-01-293050.
  9. Knowles DM, Chadburn A Lymphadenopathy and the lymphoid neoplasms associated with the acquired immune deficiency syndrome (AIDS). In: Knowles DM, ed. Neoplastic Hematopathology. Baltimore: Williams and Walker; 1992. pp. 773.
  10. Zuze T, Painschab MS, Seguin R, et al. Plasmablastic lymphoma in Malawi. Infect Agent Cancer. 2018;13:22. doi: 10.1186/s13027-018-0195-4.
  11. Liu JJ, Zhang L, Ayala E, et al. Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review. Leuk Res. 2011;35(12):1571–7. doi: 10.1016/j.leukres.2011.06.023.
  12. Tchernonog E, Faurie P, Coppo P, et al. Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group. Ann Oncol. 2017;28(4):843–8. doi: 10.1093/annonc/mdw684.
  13. Castillo JJ, Winer ES, Stachurski D, et al. Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma. Leuk Lymphoma. 2010;51(11):2047–53. doi: 10.3109/10428194.2010.516040.
  14. Morscio J, Dierickx D, Nijs J, et al. Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases. Am J Surg Pathol. 2014;38(7):875–86. doi: 10.1097/PAS.0000000000000234.
  15. Loghavi S, Alayed K, Aladily TN, et al. Stage, age, and EBV status impact outcomes of plasmablastic lymphoma patients: a clinicopathologic analysis of 61 patients. J Hematol Oncol. 2015;8:65. doi: 10.1186/s13045-015-0163-z.
  16. Bibas M, Antinori A. EBV and HIV-Related Lymphoma. Mediterr J Hematol Infect Dis. 2009;1(2):e2009032. doi: 10.4084/MJHID.2009.032.
  17. Castillo J, Pantanowitz L, Dezube BJ. HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases. Am J Hematol. 2008;83(10):804–9. doi: 10.1002/ajh.21250.
  18. Dolcetti R, Gloghini A, Caruso A, Carbone A. A lymphomagenic role for HIV beyond immune suppression? Blood. 2016;127(11):1403–9. doi: 10.1182/blood-2015-11-681411.
  19. Valera A, Balague O, Colomo L, et al. IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol. 2010;34(11):1686–94. doi: 10.1097/PAS.0b013e3181f3e29f.
  20. Montes-Moreno S, Martinez-Magunacelaya N, Zecchini-Barrese T, et al. Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1. Mod Pathol. 2017;30(1):85–94. doi: 10.1038/modpathol.2016.162.
  21. Garcia JF, Roncador G, Garcia JF, et al. PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma. Haematologica. 2006;91(4):467–74.
  22. Liu F, Asano N, Tatematsu A, et al. Plasmablastic lymphoma of the elderly: a clinicopathological comparison with age-related Epstein-Barr virus-associated B cell lymphoproliferative disorder. Histopathology. 2012;61(6):1183–97. doi: 10.1111/j.1365-2559.2012.04339.x.
  23. Boy SC, van Heerden MB, Babb C, et al. Dominant genetic aberrations and coexistent EBV infection in HIV-related oral plasmablastic lymphomas. Oral Oncol. 2011;47(9):883–7. doi: 10.1016/j.oraloncology.2011.06.506.
  24. Gruhne B, Sompallae R, Masucci MG. Three Epstein-Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints. Oncogene. 2009;28(45):3997–4008. doi: 10.1038/onc.2009.258.
  25. Price AM, Luftig MA. Dynamic Epstein-Barr virus gene expression on the path to B-cell transformation. Adv Virus Res. 2014;88:279–313. doi: 10.1016/B978-0-12-800098-4.00006-4.
  26. Ma SD, Hegde S, Young KH, et al. A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol. 2011;85(1):165–77. doi: 10.1128/JVI.01512-10.
  27. Shannon-Lowe C, Adland E, Bell AI, et al. Features distinguishing Epstein-Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J Virol. 2009;83(15):7749–60. doi: 10.1128/JVI.00108-09.
  28. Di Pietro A. Epstein-Barr Virus Promotes B Cell Lymphomas by Manipulating the Host Epigenetic Machinery. Cancers (Basel). 2020;12(10):3037. doi: 10.3390/cancers12103037.
  29. Montes-Moreno S, Gonzalez-Medina AR, Rodriguez-Pinilla SM, et al. Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype. Haematologica. 2010;95(8):1342–9. doi: 10.3324/haematol.2009.016113.
  30. Harmon CM, Smith LB. Plasmablastic Lymphoma: A Review of Clinicopathologic Features and Differential Diagnosis. Arch Pathol Lab Med. 2016;140(10):1074–8. doi: 10.5858/arpa.2016-0232-RA.
  31. Grimm KE, O’Malley DP. Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues. Ann Diagn Pathol. 2019;38:6–10. doi: 10.1016/j.anndiagpath.2018.09.014.
  32. Ramis-Zaldivar JE, Gonzalez-Farre B, Nicolae A, et al. MAP-kinase and JAK-STAT pathways dysregulation in plasmablastic lymphoma. Haematologica. 2021;106(10):2682–93. doi: 10.3324/haematol.2020.271957.
  33. Nasta SD, Carrum GM, Shahab I, et al. Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy. Leuk Lymphoma. 2002;43(2):423–6. doi: 10.1080/10428190290006260.
  34. Lester R, Li C, Phillips P, et al. Improved outcome of human immunodeficiency virus-associated plasmablastic lymphoma of the oral cavity in the era of highly active antiretroviral therapy: a report of two cases. Leuk Lymphoma. 2004;45(9):1881–5. doi: 10.1080/10428190410001697395.
  35. Armstrong R, Bradrick J, Liu YC. Spontaneous regression of an HIV-associated plasmablastic lymphoma in the oral cavity: a case report. J Oral Maxillofac Surg. 2007;65(7):1361–4. doi: 10.1016/j.joms.2005.12.039.
  36. Yordanova K, Stilgenbauer S, Bohle RM, et al. Spontaneous regression of a plasmablastic lymphoma with MYC rearrangement. Br J Haematol. 2019;186(6):e203–e207. doi: 10.1111/bjh.16082.
  37. Natkunam Y, Gratzinger D, Chadburn A, et al. Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal? Blood. 2018;132(18):1871–8. doi: 10.1182/blood-2018-04-842559.
  38. Vaubell JI, Sing Y, Ramburan A, et al. Pediatric plasmablastic lymphoma: a clinicopathologic study. Int J Surg Pathol. 2014;22(7):607–16. doi: 10.1177/1066896914531815.
  39. Jariwal R, Raza N, Bhandohal J, Cobos E. Non-Hodgkin’s Plasmablastic Lymphoma as Initial Presentation of Human Immunodeficiency Virus. J Investig Med High Impact Case Rep. 2021;9:23247096211014689. doi: 10.1177/23247096211014689.
  40. Little RF, Dunleavy K. Update on the treatment of HIV-associated hematologic malignancies. Hematology Am Soc Hematol Educ Program. 2013;2013(1):382–8. doi: 10.1182/asheducation-2013.1.382.
  41. Schommers P, Wyen C, Hentrich M, et al. Poor outcome of HIV-infected patients with plasmablastic lymphoma: results from the German AIDS-related lymphoma cohort study. AIDS. 2013;27(5):842–5. doi: 10.1097/QAD.0b013e32835e069d.
  42. Dittus C, Grover N, Ellsworth S, et al. Bortezomib in combination with dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) induces long-term survival in patients with plasmablastic lymphoma: a retrospective analysis. Leuk Lymphoma. 2018;59(9):2121–7. doi: 10.1080/10428194.2017.1416365.
  43. Barta SK, Xue X, Wang D, et al. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013;122(19):3251–62. doi: 10.1182/blood-2013-04-498964.
  44. Castillo JJ, Furman M, Beltran BE, et al. Human immunodeficiency virus-associated plasmablastic lymphoma: poor prognosis in the era of highly active antiretroviral therapy. Cancer. 2012;118(21):5270–7. doi: 10.1002/cncr.27551.
  45. Ibrahim IF, Shapiro GA, Naina HVK. Treatment of HIV-associated plasmablastic lymphoma: A single-center experience with 25 patients. J Clin Oncol. 2014;32(5 Suppl):8583. doi: 10.1200/jco.2014.32.15_suppl.8583.
  46. NCCN Guidelines Version: 4.2021. B-Cell Lymphomas. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. (accessed 20.07.2021).
  47. Antinori A, Cingolani A, Alba L, et al. Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS. 2001;15(12):1483–91. doi: 10.1097/00002030-200108170-00005.
  48. Guan B, Zhang X, Ma H, et al. Meta-analysis of highly active anti-retroviral therapy for treatment of plasmablastic lymphoma. Hematol Oncol Stem Cell Ther. 2010;3(1):7–12. doi: 10.1016/s1658-3876(10)50050-5.
  49. Francischini E, Martins FM, Braz-Silva PH, et al. HIV-associated oral plasmablastic lymphoma and role of adherence to highly active antiretroviral therapy. Int J STD AIDS. 2010;21(1):68–70. doi: 10.1258/ijsa.2008.008476.
  50. Re A, Cattaneo C, Michieli M, et al. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003;21(23):4423–7. doi: 10.1200/JCO.2003.06.039.
  51. Re A, Michieli M, Casari S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood. 2009;114(7):1306–13. doi: 10.1182/blood-2009-02-202762.
  52. Popova MO, Rogacheva YA, Nekrasova AV, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of a single center (CIC725) matched case-control study. Cell Ther Transplant. 2017;6(4):42–51. doi: 10.18620/ctt-1866-8836-2017-6-4-42-51.
  53. Popova M, Tsygankov I, Rogacheva Y, et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with HIV-related lymphoma. Annals Oncol. 2020;31(Suppl 4):S651. doi: 10.1016/j.annonc.2020.08.010.
  54. Younan P, Kowalski J, Kiem HP. Genetic modification of hematopoietic stem cells as a therapy for HIV/AIDS. Viruses. 2013;5(12):2946–62. doi: 10.3390/v5122946.
  55. Mock U, Machowicz R, Hauber I, et al. mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5. Nucl Acids Res. 2015;43(11):5560–71. doi: 10.1093/nar/gkv469.
  56. Wang CX, Cannon PM. The clinical applications of genome editing in HIV. 2016;127(21):2546–52. doi: 10.1182/blood-2016-01-678144.
  57. Попова М.О., Сергеев В.С., Лепик К.В. и др. Генная клеточная терапия ВИЧ и злокачественных опухолей кроветворной и лимфатической ткани на основе трансплантации гемопоэтических стволовых клеток с использованием сайт-специфического редактирования генома. Журнал инфектологии. 2017;9(1):31–9. doi: 10.22625/2072-6732-2017-9-1-31-39.
    [Popova MО, Sergeev VS, Lepik KV, et al. Gene-Cell Therapy of HIV and Hematological Malignances Based on Hematopoietic Stem Cell Transplantation and Site-Specific Genome Editing. Journal Infectology. 2017;9(1):31–9. doi: 10.22625/2072-6732-2017-9-1-31-39. (In Russ)]
  58. Morgan RA, Gray D, Lomova A, et al. Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned. Cell Stem Cell. 2017;21(5):574–90. doi: 10.1016/j.stem.2017.10.010.
  59. Popova MO, Lepik KV, Sergeev VS, et al. Clinical implementation of genome editing for correction of human diseases. Cell Ther Transplant. 2017;6(1):37–43. doi: 10.18620/ctt-1866-8836-2017-6-1-37-43.
  60. Serrano D, Carrion R, Balsalobre P, et al. Spanish Cooperative Groups GELTAMO and GESIDA. HIV-associated lymphoma successfully treated with peripheral blood stem cell transplantation. Exp Hematol. 2005;33(4):487–94. doi: 10.1016/j.exphem.2004.12.008.
  61. Bowden RA, Coombs RW, Nikora BH, et al. Progression of human immunodeficiency virus type-1 infection after allogeneic marrow transplantation. Am J Med. 1990;88(5N):49N–52N.
  62. Al-Malki MM, Castillo JJ, Sloan JM, et al. Hematopoietic cell transplantation for plasmablastic lymphoma: a review. Biol Blood Marrow Transplant. 2014;20(12):1877–84. doi: 10.1016/j.bbmt.2014.06.009.
  63. Gupta V, Tomblyn M, Pedersen TL, et al. Allogeneic hematopoietic cell transplantation in human immunodeficiency virus-positive patients with hematologic disorders: a report from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15(7):864–71. doi: 10.1016/j.bbmt.2009.03.023.
  64. Hamadani M, Devine SM. Reduced-intensity conditioning allogeneic stem cell transplantation in HIV patients with hematologic malignancies: yes, we can. Blood. 2009;114(12):2564–6. doi: 10.1182/blood-2009-06-229666.
  65. Afanasyev BV, Popova MO, Bondarenko SN, et al. St. Petersburg experience of allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and human immunodeficiency virus. Cell Ther Transplant. 2015;4(1–2):24–30. doi: 10.18620/1866-8836-2015-4-1-2-24-30.
  66. Yoon JH, Jeon YW, Lee SE, et al. Allogeneic stem cell transplantation using lymphoablative rather than myeloablative conditioning regimen for relapsed or refractory lymphomas. Hematol Oncol. 2017;35(1):17–24. doi: 10.1002/hon.2201.
  67. Rong C, Sheng L, Wu A, et al. Allogeneic hematopoietic stem cell transplantation in a patient with HIV-negative recurrent plasmablastic lymphoma: A case report. Medicine (Baltimore). 2021;100(7):e24498. doi: 10.1097/MD.0000000000024498.
  68. Lepik KV, Mikhailova NB, Moiseev IS, et al. Nivolumab for the treatment of relapsed and refractory classical Hodgkin lymphoma after ASCT and in ASCT-naive patients. Leuk Lymphoma. 2019;60(9):2316–9. doi: 10.1080/10428194.2019.1573368.
  69. Ambinder RF, Wu J, Logan B, et al. Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies: The BMT CTN-0903/AMC-080 Trial. Biol Blood Marrow Transplant. 2019;25(11):2160–6. doi: 10.1016/j.bbmt.2019.06.033.
  70. Umeanaeto O, Gamboa J, Diaz J, et al. Incorporating Bortezomib in the Management of Plasmablastic Lymphoma. Anticancer Res. 2019;39(9):5003–7. doi: 10.21873/anticanres.13690.
  71. Castillo JJ, Reagan JL, Sikov W, et al. Bortezomib in combination with infusional dose-adjusted EPOCH for the treatment of plasmablastic lymphoma. Br J Haematol. 2015;169(3):352–5. doi: 10.1111/bjh.1330.
  72. Cao C, Liu T, Zhu H, et al. Bortezomib-contained chemotherapy and thalidomide combined with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) play promising roles in plasmablastic lymphoma: a case report and literature review. Clin Lymphoma Myeloma Leuk. 2014;14(5):e145–е150. doi: 10.1016/j.clml.2014.03.002.
  73. Cencini E, Fabbri A, Guerrini S, et al. Long-term remission in a case of plasmablastic lymphoma treated with COMP (cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) and bortezomib. Eur J Haematol. 2016;96(6):650–4. doi: 10.1111/ejh.12732.
  74. Colomo L, Loong F, Rives S, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol. 2004;28(6):736–47. doi: 10.1097/01.pas.0000126781.87158.e3.
  75. Holderness BM, Malhotra S, Levy NB, Danilov AV. Brentuximab vedotin demonstrates activity in a patient with plasmablastic lymphoma arising from a background of chronic lymphocytic leukemia. J Clin Oncol. 2013;31(12):e197–е199. doi: 10.1200/JCO.2012.46.9593.
  76. Pretscher D, Kalisch A, Wilhelm M, et al. Refractory plasmablastic lymphoma-a review of treatment options beyond standard therapy. Ann Hematol. 2017;96(6):967–70. doi: 10.1007/s00277-016-2904-7.
  77. Laurent C, Fabiani B, Do C, et al. Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients. Haematologica. 2016;101(8):976–84. doi: 10.3324/haematol.2016.141978.
  78. Damlaj M, Alzayed M, Alahmari B, et al. Therapeutic Potential of Checkpoint Inhibitors in Refractory Plasmablastic Lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19(10):e559–e563. doi: 10.1016/j.clml.2019.06.008.
  79. Popova M, Rogacheva Y, Tsygankov I, et al. Immunotherapy in patients with relapsed/refractory HIV-related lymphomas. Annals Oncol. 2019;30(11):XI22. doi: 10.1093/annonc/mdz449.015.
  80. Lepik KV, Mikhailova NB, Kondakova EV, et al. A Study of Safety and Efficacy of Nivolumab and Bendamustine (NB) in Patients With Relapsed/Refractory Hodgkin Lymphoma After Nivolumab Monotherapy Failure. Hemasphere. 2020;4(3):e401. doi: 10.1097/HS9.0000000000000401.
  81. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/JCO.2013.54.8800.
  82. Каприн А.Д., Старинский В.В., Шахзадова А.О. Состояние онкологической помощи населению России в 2019 году. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020. [Kaprin AD, Starinskii VV, Shakhzadova AO. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2019 godu. (The state of cancer care in Russia in 2019.) Moscow: MNIOI im. P.A. Gertsena — filial FGBU “NMITs radiologii” Publ.; (In Russ)]
  83. Информационные бюллетени Федерального научно-методического центра по профилактике и борьбе со СПИДом: Бюллетень № 40 (электронный документ). Доступно по: http://www.hivrussia.ru/files/bulpdf. Ссылка активна на 20.07.2021.
    [Information Bulletins of Federal Scientific and Methodological Center for the Prevention and Control of AIDS: Bulletin No. 40 (Internet). Available from: http://www.hivrussia.ru/files/bul_40.pdf. (accessed 20.07.2021) (In Russ)]

Artificial Intelligence in Hematology

AUTOIMMUNE THROMBOCYTOPENIA

“Artificial intelligence will not replace physicians, however, those physicians who use artificial

intelligence will replace those who don’t.”

Dr. Bertalan Mesko, the medical futurist

AS Luchinin

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

For correspondence: Aleksandr Sergeevich Luchinin, MD, PhD, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS. Artificial Intelligence in Hematology. Clinical oncohematology. 2022;15(1):16–27. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-16-27

ABSTRACT

‘Artificial Intelligence’ is a general term to designate computer technologies for solving the problems that require implementation of human intelligence, for example, human voice or image recognition. Most artificial intelligence products with application in healthcare are associated with machine learning, i.e., a field of informatics and statistics dealing with the generation of predictive or descriptive models through data-based learning, rather than programming of strict rules. Machine learning has been widely used in pathomorphology, radiology, genomics, and electronic medical record data analysis. In line with the current trend, artificial intelligence technologies will most likely become increasingly integrated into health research and practice, including hematology. Thus, artificial intelligence and machine learning call for attention and understanding on the part of researchers and clinical physicians. The present review covers important terms and basic concepts of these technologies, as well as offers examples of their actual use in hematological research and practice.

Keywords: artificial intelligence, machine learning, neural network.

Received: September 23, 2021

Accepted: December 15, 2021

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Статистика Plumx английский

REFERENCES

  1. Muhsen IN, Shyr D, Sung AD, Hashmi SK. Machine Learning Applications in the Diagnosis of Benign and Malignant Hematological Diseases. Clin Hematol Intern. 2021;3(1):13–20. doi: 10.2991/chi.k.201130.001.
  2. Radakovich N, Nagy M, Nazha A. Machine learning in haematological malignancies. Lancet Haematol. 2020;7(7):e541–e550. doi: 10.1016/S2352-3026(20)30121-6.
  3. Deo RC. Machine Learning in Medicine. Circulation. 2015;132(20):1920–30. doi: 10.1161/CIRCULATIONAHA.115.001593.
  4. Miotto R, Wang F, Wang S, et al. Deep learning for healthcare: review, opportunities and challenges. Brief Bioinform. 2018;19(6):1236–46. doi: 10.1093/bib/bbx044.
  5. Esteva A, Robicquet A, Ramsundar B, et al. A guide to deep learning in healthcare. Nat Med. 2019;25(1):24–9. doi: 10.1038/s41591-018-0316-z.
  6. Komura D, Ishikawa S. Machine learning approaches for pathologic diagnosis. Virchows Arch. 2019;475(2):131–8. doi: 10.1007/s00428-019-02594-w.
  7. Sha L, Osinski BL, Ho IY, et al. Multi-Field-of-View Deep Learning Model Predicts Nonsmall Cell Lung Cancer Programmed Death-Ligand 1 Status from Whole-Slide Hematoxylin and Eosin Images. J Pathol Inform. 2019;10(1):24. doi: 10.4103/jpi.jpi_24_19.
  8. Abramoff MD, Lavin PT, Birch M, et al. Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices. NPJ Digit Med. 2018;1(1):39. doi: 10.1038/s41746-018-0040-6.
  9. Benjamens S, Dhunnoo P, Mesko B. The state of artificial intelligence-based FDA-approved medical devices and algorithms: an online database. NPJ Digit Med. 2020;3(1):118. doi: 10.1038/s41746-020-00324-0.
  10. Shouval R, Fein JA, Savani B, et al. Machine learning and artificial intelligence in haematology. Br J Haematol. 2021;192(2):239–50. doi: 10.1111/bjh.16915.
  11. Shahid AH, Singh MP. Computational intelligence techniques for medical diagnosis and prognosis: problems and current developments. Biocybern Biomed Eng. 2019;39(3):638–72. doi: 10.1016/j.bbe.2019.05.010.
  12. Морозов С.П., Владзимирский А.В., Кляшторный В.Г. и др. Клинические испытания программного обеспечения на основе интеллектуальных технологий (лучевая диагностика). Лучшие практики лучевой и инструментальной диагностики. Препринт № ЦДТ-2019-1. М., 2019. 34 с.
    [Morozov SP, Vladzimirskii AV, Klyashtornyi VG, et al. Clinical acceptance of software based on artificial intelligence technologies (radiology). Preprint No. CDT-2019-1. Luchshie praktiki luchevoi i instrumental’noi diagnostiki. (Best practices in medical imaging.) Moscow; 2019. 34 (In Russ)]
  13. Shekelle PG, Shetty K, Newberry S, et al. Machine Learning Versus Standard Techniques for Updating Searches for Systematic Reviews: A Diagnostic Accuracy Study. Ann Intern Med. 2017;167(3):213–5. doi: 10.7326/L17-0124.
  14. Kimura K, Tabe Y, Ai T, et al. A novel automated image analysis system using deep convolutional neural networks can assist to differentiate MDS and AA. Sci Rep. 2019;9(1):13385. doi: 10.1038/s41598-019-49942-z.
  15. Wang Q, Bi S, Sun M, et al. Deep learning approach to peripheral leukocyte recognition. PLoS One. 2019;14(6):e0218808. doi: 10.1371/journal.pone.0218808.
  16. Hegde RB, Prasad K, Hebbar H, Singh BMK. Comparison of traditional image processing and deep learning approaches for classification of white blood cells in peripheral blood smear images. Biocybern Biomed Eng. 2019;39(2):382–92. doi: 10.1016/j.bbe.2019.01.005.
  17. Syrykh C, Abreu A, Amara N, et al. Accurate diagnosis of lymphoma on whole-slide histopathology images using deep learning. NPJ Digit Med. 2020;3(1):63. doi: 10.1038/s41746-020-0272-0.
  18. Achi HE, Belousova T, Chen L, et al. Automated Diagnosis of Lymphoma with Digital Pathology Images Using Deep Learning. Ann Clin Lab Sci. 2019;49(2):153–60.
  19. Sheng B, Zhou M, Hua M, et al. A blood cell dataset for lymphoma classification using faster R-CNN. Biotechnol Biotechnol Equip. 2020;34(1):413–20. doi: 10.1080/13102818.2020.1765871.
  20. Xu L, Tetteh G, Lipkova J, et al. Automated Whole-Body Bone Lesion Detection for Multiple Myeloma on (68)Ga-Pentixafor PET/CT Imaging Using Deep Learning Methods. Contrast Media Mol Imaging. 2018;2018:1–11. doi: 10.1155/2018/2391925.
  21. Martinez-Martinez F, Kybic J, Lambert L, Meckova Z. Fully automated classification of bone marrow infiltration in low-dose CT of patients with multiple myeloma based on probabilistic density model and supervised learning. Comput Biol Med. 2016;71:57–66. doi: 10.1016/j.compbiomed.2016.02.001.
  22. Wang L, Zhao Z, Luo Y, et al. Classifying 2-year recurrence in patients with DLBCL using clinical variables with imbalanced data and machine learning methods. Comput Meth Program Biomed. 2020;196:105567. doi: 10.1016/j.cmpb.2020.105567.
  23. Biccler JL, Eloranta S, de Nully Brown P, et al. Optimizing Outcome Prediction in Diffuse Large B-Cell Lymphoma by Use of Machine Learning and Nationwide Lymphoma Registries: A Nordic Lymphoma Group Study. JCO Clin Cancer Inform. 2018;2:1–13. doi: 10.1200/CCI.18.00025.
  24. Guncar G, Kukar M, Notar M, et al. An application of machine learning to haematological diagnosis. Sci Rep. 2018;8(1):411. doi: 10.1038/s41598-017-18564-8.
  25. Breiman L. Random forests. Machine Learning. 2001;45:5–32. doi: 1023/A:1010933404324.
  26. Nazha A, Komrokji RS, Meggendorfer M, et al. A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes. Blood. 2018;132(Suppl 1):793. doi: 10.1182/blood-2018-99-114774.
  27. Hu SB, Wong DJ, Correa A, et al. Prediction of Clinical Deterioration in Hospitalized Adult Patients with Hematologic Malignancies Using a Neural Network Model. PLoS One. 2016;11(8):e0161401. doi: 10.1371/journal.pone.0161401.
  28. Prochazka VK, Matustikova S, Furst T, et al. Bayesian Network Modelling As a New Tool in Predicting of the Early Progression of Disease in Follicular Lymphoma Patients. Blood. 2020;136(Suppl 1):20–1. doi: 10.1182/blood-2020-139830.
  29. Mahmood N, Shahid S, Bakhshi T, et al. Identification of significant risks in pediatric acute lymphoblastic leukemia (ALL) through machine learning (ML) approach. Med Biol Eng Comput. 2020;58(11):2631–40. doi: 10.1007/s11517-020-02245-2.
  30. Gandelman JS, Byrne MT, Mistry AM, et al. Machine learning reveals chronic graft-versus-host disease phenotypes and stratifies survival after stem cell transplant for hematologic malignancies. Haematologica. 2019;104(1):189–96. doi: 10.3324/haematol.2018.193441.
  31. Chen D, Goyal G, Go RS, et al. Improved Interpretability of Machine Learning Model Using Unsupervised Clustering: Predicting Time to First Treatment in Chronic Lymphocytic Leukemia. JCO Clin Cancer Inform. 2019;3:1–11. doi: 10.1200/CCI.18.00137.
  32. Coombes CE, Abrams ZB, Li S, et al. Unsupervised machine learning and prognostic factors of survival in chronic lymphocytic leukemia. J Am Med Inform Assoc. 2020;27(7):1019–27. doi: 10.1093/jamia/ocaa060.
  33. Shah P, Kendall F, Khozin S, et al. Artificial intelligence and machine learning in clinical development: a translational perspective. NPJ Digit Med. 2019;2(1):69. doi: 10.1038/s41746-019-0148-3.
  34. Shouval R, Labopin M, Bondi O, et al. Prediction of Allogeneic Hematopoietic Stem-Cell Transplantation Mortality 100 Days After Transplantation Using a Machine Learning Algorithm: A European Group for Blood and Marrow Transplantation Acute Leukemia Working Party Retrospective Data Mining Study. J Clin Oncol. 2015;33(28):3144–51. doi: 10.1200/JCO.2014.59.1339.
  35. Nazha A, Hu ZH, Wang T, et al. A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Cell Transplant in Patients with Myelodysplastic Syndromes. Biol Blood Marrow Transplant. 2020;26(11):2139–46. doi: 10.1016/j.bbmt.2020.08.003.
  36. Bigorra L, Larriba I, Gutierrez-Gallego R. Machine learning algorithms for accurate differential diagnosis of lymphocytosis based on cell population data. Br J Haematol. 2019;184(6):1035–7. doi: 10.1111/bjh.15230.
  37. Nazha A, Sekeres MA, Bejar R, et al. Genomic Biomarkers to Predict Resistance to Hypomethylating Agents in Patients with Myelodysplastic Syndromes Using Artificial Intelligence. JCO Precis Oncol. 2019;3:1–11. doi: 10.1200/po.19.00119.
  38. Milgrom SA, Elhalawani H, Lee J, et al. A PET Radiomics Model to Predict Refractory Mediastinal Hodgkin Lymphoma. Sci Rep. 2019;9(1):1322. doi: 10.1038/s41598-018-37197-z.
  39. Moraes LO, Pedreira CE, Barrena S, et al. A decision-tree approach for the differential diagnosis of chronic lymphoid leukemias and peripheral B-cell lymphomas. Comput Meth Program Biomed. 2019;178:85–90. doi: 10.1016/j.cmpb.2019.06.014.
  40. Ni W, Hu B, Zheng C, et al. Automated analysis of acute myeloid leukemia minimal residual disease using a support vector machine. Oncotarget. 2016;7(44):71915–21. doi: 10.18632/oncotarget.12430.
  41. Fuse K, Uemura S, Tamura S, et al. Patient-based prediction algorithm of relapse after allo-HSCT for acute Leukemia and its usefulness in the decision-making process using a machine learning approach. Cancer Med. 2019;8(11):5058–67. doi: 10.1002/cam4.2401.
  42. Goswami C, Poonia S, Kumar L, Sengupta D. Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation. Front Oncol. 2019;9:633. doi: 10.3389/fonc.2019.00633.
  43. Gal O, Auslander N, Fan Y, Meerzaman D. Predicting Complete Remission of Acute Myeloid Leukemia: Machine Learning Applied to Gene Expression. Cancer Inform. 2019;18:1–5. doi: 10.1177/1176935119835544.
  44. Huang S, Yang J, Fong S, Zhao Q. Artificial intelligence in cancer diagnosis and prognosis: Opportunities and challenges. Cancer Lett. 2020;471:61–71. doi: 10.1016/j.canlet.2019.12.007.
  45. Ubels J, Sonneveld P, van Beers EH, et al. Predicting treatment benefit in multiple myeloma through simulation of alternative treatment effects. Nat Commun. 2018;9(1):2943. doi: 10.1038/s41467-018-05348-5.
  46. Shain KH, Hart D, Silva AS, et al. Reinforcement Learning to Optimize the Treatment of Multiple Myeloma. Blood. 2019;134(Suppl_1):5511. doi: 10.1182/blood-2019-132234.
  47. Mateos MV, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019;6(9):e459–e469. doi: 10.1016/S2352-3026(19)30110-3.
  48. Liao JJZ, Farooqui MZH, Marinello P, et al. Using artificial intelligence tools in answering important clinical questions: The KEYNOTE-183 multiple myeloma experience. Contemp Clin Trials. 2020;99:106179. doi: 10.1016/j.cct.2020.106179.
  49. Третье мнение. AI для клинической лабораторной диагностики (электронный документ). Доступно по: https://thirdopinion.ai/ru#rec Ссылка активна на 06.10.2021.
    [Third Opinion. AI for clinical laboratory diagnostics (Internet). Available from: https://thirdopinion.ai/ru#rec354556522 (accessed 06.10.2021). (In Russ)]

A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation

AUTOIMMUNE THROMBOCYTOPENIA , ,

EN Parovichnikova1, TTs Garmaeva1, OV Lazareva1, KA Lukina1, YuA Chabaeva1, SM Kulikov1, VV Troitskaya1, TV Gaponova1, LI Menshikova2, VG Savchenko1

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

2 Federal Research Institute for Health Organization and Informatics, 11 Dobrolyubova str., Moscow, Russian Federation, 127254

For correspondence: Elena Nikolaevna Parovichnikova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: parovichnikova@gmail.com

For citation: Parovichnikova EN, Garmaeva TTs, Lazareva OV, et al. A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation. Clinical oncohematology. 2022;15(1):1–15. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-1-15

ABSTRACT

Background. Since 2018 a widespread national project “Healthcare” has been implemented in the Russian Federation (RF) to improve the quality, efficiency, availability, and affordability of medical care in the profiles of specialties in constituent entities of the RF. Modern hematology as a medical field of high technology and crucial solutions is notable for its multi- and interdisciplinarity of most nosological forms, complexity of diagnostic process, multi-structuredness and diversity of related physician teams in different structural units and subdivisions. One of the key issues in federal projects is to determine the indicators for assessing the efficiency of regional hematological services in constituent entities of the RF.

Aim. To elaborate and substantiate a new integrated operational efficiency index for hematological services in constituent entities of the RF.

Materials & Methods. The analysis of data and assessment of feasibility of a new integrated operational index “early mortality in acute leukemia” (AL) were based on the results of 5 multi-center trials, including an epidemiological one.

Results. Multi-center clinical studies on AL are the only objective tools for assessing the treatment efficacy, its improvement, and further training of hematologists taking part in the trials. AL treatment requires well-developed infrastructure of hematological services involving not only staff matters and organization of hematologists’ activities, but also management of many highly important related subdivisions and laboratories, logistics of their interaction, time specifications, meeting clinical guidelines, and lastly, and most importantly, financial support.

Conclusion. The Unified State Information System “Hematology” is the only platform providing the objective information on patients’ vital status and enabling the use of the suggested integrated index for assessing the quality and efficiency of hematological services in the regions of the RF. This indicator of early mortality in AL patients less than 60 years of age is 15 % for acute myeloid leukemias and 10 % for acute lymphoblastic leukemias. Its low values would demonstrate that this or that constituent entity of the RF is provided with sufficient infrastructure, technologies, and a professional team to keep those patients alive who have severe but curable hematological diseases. The indicator of long-term survival or “life years gained” should become the main strategic criterion for the therapy efficacy in hematological diseases.

Keywords: hematological services, assessment of the medical care quality, early mortality, overall survival, acute leukemia, acute myeloid leukemia, acute lymphoblastic leukemia.

Received: September 27, 2021

Accepted: December 15, 2021

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REFERENCES

  1. Приказ Минздрава России от 29.12.2012г. № 1706 «Об утверждении методических рекомендаций по разработке органами исполнительной власти субъектов Российской Федерации планов мероприятий («дорожных карт») «Изменения в отраслях социальной сферы, направленные на повышение эффективности здравоохранения в субъекте Российской Федерации».
    [Decree No. 1706 of the Ministry of Health of the Russian Federation dated December 29, 2012. On the approval of methodological guidelines for the development of action plans (roadmaps) by the executive authorities of constituent entities of the Russian Federation. Changes in the social sectors aimed at improving the efficiency of healthcare in constituent entities of the Russian Federation. (In Russ)]
  2. Валиев Т.Т., Шервашидзе М.А., Осипова И.В. и др. Лечение острого лимфобластного лейкоза у детей по протоколу ALL IC-BFM 2002: результаты мультицентрового ретроспективного исследования. Российский журнал детской гематологии и онкологии. 2021;8(3):59–70. doi: 10.21682/2311-1267-2021-8-3-59-70.
    [Valiev TT, Shervashidze MA, Osipova IV, et al. Treatment of acute lymphoblastic leukemia in children by ALL IC-BFM 2002 protocol: results of multicenter retrospective study. Russian Journal of Pediatric Hematology and Oncology. 2021;8(3):59–70. doi: 10.21682/2311-1267-2021-8-3-59-70. (In Russ)]
  3. Шервашидзе М.А., Валиев Т.Т. Совершенствование программ терапии острого лимфобластного лейкоза у детей: акцент на минимальную остаточную болезнь. Онкогематология. 2020;15(3):12–26. doi: 10.17650/1818­8346­2020­15­3­12­26.
    [Shervashidze MA, Valiev TT. Pediatric acute lymphoblastic leukemia treatment protocols improvement: emphasis on minimal residual disease. Oncohematology. 2020;15(3):12–26. doi: 10.17650/1818­8346­2020­15­3­12­26. (In Russ)]
  4. Berwick D, Fox D. Evaluating the Quality of Medical Care: Donabedian’s Classic Article 50 Years Later. Milbank Q. 2016;94(2):237–41. doi: 10.1111/1468-0009.12189.
  5. Donabedian A. Evaluating the quality of medical care. Milbank Q. 2005;83(4):691–729. doi: 10.1111/j.1468-0009.2005.00397.x.
  6. Mengis C, Aebi S, Tobler A, et al. Assessment of differences in patient populations selected for excluded from participation in clinical phase III acute myelogenous leukemia trials. J Clin Oncol. 2003;21(21):3933–9. doi: 10.1200/JCO.2003.03.186.
  7. Гармаева Т.Ц., Савченко В.Г., Лазарева О.В. и др. Организация выездных мероприятий с посещением профильных медицинских организаций (МО) субъектов РФ. Гематология и трансфузиология. 2020;65(S1):65.
    [Garmaeva TTs, Savchenko VG, Lazareva OV, et al. Organization of offsite events with visiting specialized healthcare organizations (HO) of constituent entities of the Russian Federation. Gematologiya i transfuziologiya. 2020;65(S1):65. (In Russ)]
  8. Федеральный закон от 29.07.2017 № 242-ФЗ «О внесении изменений в отдельные законодательные акты Российской Федерации по вопросам применения информационных технологий в сфере охраны здоровья».
    [Federal Law No. 242-FZ dated July 29, 2017. On amendments to certain legislative acts of the Russian Federation on information technology for health protection. (In Russ)]
  9. Злокачественные новообразования в России в 2019году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020. 252 с.
    [Kaprin AD, Starinskii VV, Shakhzadova AO, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2019 godu (zabolevaemost’ i smertnost’). (Malignant neoplasms in Russia in 2019 (incidence and mortality.) Moscow: MNIOI im. P.A. Gertsena — filial FGBU “NMITs radiologii” Publ.; 252 p. (In Russ)]
  10. Савченко В.Г., Паровичникова Е.Н., Клясова Г.А. и др. Итоги многоцентрового кооперированного исследования по лечению острых миелоидных лейкозов взрослых. Терапевтический архив. 1994;66(7):11–7.
    [Savchenko VG, Parovichnikova EN, Klyasova GA, et al. Results of a multicenter collaborative study on the treatment of acute myeloid leukemia in adults. Terapevticheskii arkhiv. 1994;66(7):11–7. (In Russ)]
  11. Савченко В.Г., Паровичникова Е.Н., Клясова Г.А., Исаев В.Г. Итоги двух с половиной лет работы российского многоцентрового исследования по лечению острых лейкозов взрослых. Терапевтический архив. 1995;67(7):8–12.
    [Savchenko VG, Parovichnikova EN, Klyasova GA, Isaev VG. Results of a two-and-a-half-year Russian multicenter study on the treatment of acute leukemia in adults. Terapevticheskii arkhiv. 1995;67(7):8–12. (In Russ)]
  12. Савченко В.Г., Паровичникова Е.Н., Клясова Г.А. и др. Результаты проводимых в течение 7 лет клинических исследований по лечению острых миелоидных лейкозов взрослых. Терапевтический архив. 1999;71(7):13–20.
    [Savchenko VG, Parovichnikova EN, Klyasova GA, et al. Results of 7-year clinical studies on the treatment of acute myeloid leukemia in adults. Terapevticheskii arkhiv. 1999;71(7):13–20. (In Russ)]
  13. Савченко В.Г., Паровичникова Е.Н., Исаев В.Г. и др. Лечение острых лимфобластных лейкозов взрослых как нерешенная проблема. Терапевтический архив. 2001;73(7):6–15.
    [Savchenko VG, Parovichnikova EN, Isaev VG, et al. Treatment of acute lymphoblastic leukemia in adults as an unsolved problem. Terapevticheskii arkhiv. 2001;73(7):6–15. (In Russ)]
  14. Савченко В.Г., Паровичникова Е.Н., Менделеева Л.П. и др. Многоцентровая кооперация — основа прогресса в лечении лейкозов. Терапевтический архив. 2005;77(7):5–11.
    [Savchenko VG, Parovichnikova EN, Mendeleeva LP, et al. Multicenter cooperation is a basis of progress in the treatment of leukemia. Terapevticheskii arkhiv. 2005;77(7):5–11. (In Russ)]
  15. Паровичникова Е.Н., Савченко В.Г., Исаев В.Г. и др. Итоги многоцентрового рандомизированного исследования по лечению острых миелоидных лейкозов взрослых. Терапевтический архив. 2007;79(7):14–9.
    [Parovichnikova EN, Savchenko VG, Isaev VG, et al. Results of a multicenter randomized study on the treatment of acute myeloid leukemia in adults. Terapevticheskii arkhiv. 2007;79(7):14–9. (In Russ)]
  16. Паровичникова Е.Н., Савченко В.Г., Клясова Г.А. и др. Токсичность различных протоколов лечения острых миелоидных лейкозов взрослых: результат четырех российских многоцентровых исследований. Терапевтический архив. 2010;82(7):5–11.
    [Parovichnikova EN, Savchenko VG, Klyasova GA, et al. Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies. Terapevticheskii arkhiv. 2010;82(7):5–11. (In Russ)]
  17. Соколов А.Н., Паровичникова Е.Н., Куликов С.М. и др. Долгосрочные результаты лечения острых миелоидных лейкозов у взрослых в многоцентровом клиническом исследовании ОМЛ 06.06. Клиническая онкогематология. 2012;5(1):30–8.
    [Sokolov AN, Parovichnikova EN, Kulikov SM, et al. Long-term results of acute myeloid leukemia treatment in adults in a multicenter clinical study of AML 06.06. Klinicheskaya onkogematologiya. 2012;5(1):30–8. (In Russ)]
  18. Паровичникова Е.Н., Клясова Г.А., Соколов А.Н. и др. Первые результаты лечения острых миелоидных лейкозов взрослых по протоколу ОМЛ-01.10 Научно-исследовательской группы гематологических центров России. Терапевтический архив. 2012;84(7):10–5.
    [Parovichnikova EN, Klyasova GA, Sokolov AN, et al. The first results of acute myeloid leukemia treatment in adults according to the AML-01.10 protocol of the Research Group of Hematological Centers in Russia. Terapevticheskii arkhiv. 2012;84(7):10–5. (In Russ)]
  19. Паровичникова Е.Н., Троицкая В.В., Клясова Г.А. и др. Лечение больных острыми миелоидными лейкозами по протоколу российского многоцентрового рандомизированного исследования ОМЛ-01.10: результаты координационного центра. Терапевтический архив. 2014;86(7):14–23.
    [Parovichnikova EN, Troitskaya VV, Klyasova GA, et al. Treating patients with acute myeloid leukemias (AML) according to the protocol of the AML-01.10 Russian multicenter randomized trial: the coordinating center’s results. Terapevticheskii arkhiv. 2014;86(7):14–23. (In Russ)]
  20. Паровичникова Е.Н., Лукьянова И.А., Троицкая В.В. и др. Результаты программной терапии острых миелоидных лейкозов в ФГБУ «НМИЦ гематологии» Минздрава России. Терапевтический архив. 2018;90(7):14–22.
    [Parovichnikova EN, Lukyanova IA, Troitskaya VV, et al. Results of the program therapy of acute myeloid leukemia in the FGBU “NMITS Gematologii” of the Ministry of Health of Russia. Terapevticheskii arkhiv. 2018;90(7):14–22. (In Russ)]
  21. Buchner T, Schlenk RF, Schaich M, et al. Acute Myeloid Leukemia (AML): Different Treatment Strategies Versus a Common Standard Arm—Combined Prospective Analysis by the German AML Intergroup. J Clin Oncol. 2012;30(29):3604–10. doi: 10.1200/JCO.2012.42.2907.
  22. Othus M, Kantarjian H, Petersdorf S, et al Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. 2013;28(2):289–92. doi: 10.1038/leu.2013.176.
  23. Паровичникова Е.Н., Давидян Ю.Р., Исаев В.Г. и др. Итоги лечения острых лимфобластных лейкозов взрослых по протоколу ОЛЛ-2005 как основа для новых исследований. Терапевтический архив. 2009;81(7):8–15.
    [Parovichnikova EN, Davidyan YuR, Isaev VG, et al. Results of acute lymphoblastic leukemia treatment in adults according to the ALL-2005 protocol as a basis for new research. Terapevticheskii arkhiv. 2009;81(7):8–15. (In Russ)]
  24. Паровичникова Е.Н., Клясова Г.А., Троицкая В.В. и др. Эффективность лечения взрослых больных острым Т-лимфобластным лейкозом по протоколу ОЛЛ-2009 российской научно-исследовательской группы по изучению острых лейкозов. Терапевтический архив. 2013;85(8):29–34.
    [Parovichnikova EN, Klyasova GA, Troitskaya VV, et al. The efficacy of acute T-lymphoblastic leukemia treatment in adults according to the ALL-2009 protocol of the Russian research group for the study of acute leukemia. Terapevticheskii arkhiv. 2013;85(8):29–34. (In Russ)]
  25. Паровичникова Е.Н., Троицкая В.В., Соколов А.Н. и др. Промежуточные результаты по лечению острых Ph-негативных лимфобластных лейкозов у взрослых больных (итоги российской исследовательской группы по лечению острых лимфобластных лейкозов (RALL)). Онкогематология. 2014;9(3):6–15.
    [Parovichnikova EN, Troitskaya VV, Sokolov AN, et al. Interim outcomes of acute Ph-negative lymphoblastic leukemia treatment in adults (results of the Russian research group on the treatment of acute lymphoblastic leukemias (RALL)). Onkogematologiya. 2014;9(3):6–15. (In Russ)]
  26. Паровичникова Е.Н., Соколов А.Н., Троицкая В.В. и др. Острые Ph-негативные лимфобластные лейкозы взрослых: факторы риска при использовании протокола ОЛЛ-2009. Терапевтический архив. 2016;88(7):15–24.
    [Parovichnikova EN, Sokolov AN, Troitskaya VV, et al. Acute Ph-negative lymphoblastic leukemias in adults: ALL-2009 protocol risk factors. Terapevticheskii arkhiv. 2016;88(7):15–24. (In Russ)]
  27. Паровичникова Е.Н., Троицкая В.В., Соколов А.Н. и др. Острые В-лимфобластные лейкозы взрослых: выводы из российского проспективного многоцентрового исследования ОЛЛ-2009. Терапевтический архив. 2017;89(7):10–7.
    [Parovichnikova EN, Troitskaya VV, Sokolov AN, et al. Acute B-lymphoblastic leukemia in adults: findings of the Russian prospective multicenter study ALL-2009. Terapevticheskii arkhiv. 2017;89(7):10–7. (In Russ)]
  28. Gokbuget N, Beck J, Brandt K. Significant Improvement Of Outcome In Adolescents and Young adults (AYAs) Aged 15–35 Years With Acute Lymphoblastic Leukemia (ALL) With a Pediatric Derived Adult ALL Protocol; Results Of 1529 AYAs In 2 Consecutive Trials Of The German Multicenter Study Group For Adult ALL (GMALL). 2013;22(21):839. doi: 10.1182/blood.V122.21.839.839.
  29. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. 2005;106(12):3760–7. doi: 10.1182/blood-2005-04-1623.
  30. Francoise H, Thibaut L, Emmanuel R, et al. Pediatric-Inspired Therapy in Adults With Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 Study. J Clin Oncol. 2009;27(6):911–8. doi:1200/JCO.2008.18.6916.
  31. Гайдамака Н.В., Паровичникова Е.Н., Гармаева Т.Ц. и др. Длительные аплазии костного мозга после химиотерапии у больных острыми лейкозами. Терапевтический архив. 2010;82(7):29–34.
    [Gaidamaka NV, Parovichnikova EN, Garmaeva TTs, et al. Long-term bone marrow aplasias after chemotherapy in acute leukemia patients. Terapevticheskii arkhiv. 2010;82(7):29–34. (In Russ)]
  32. Алгоритмы диагностики и программная терапия заболеваний системы крови. Под ред. В.Г. Савченко. М.: Практика, 2018.
    [Savchenko VG, ed. Algoritmy diagnostiki i programmnaya terapiya zabolevanii sistemy krovi. (Diagnostic algorithms and program therapy for hematological diseases.) Moscow: Praktika Publ.; 2018. (In Russ)]
  33. Ахмерзаева З.Х., Паровичникова Е.Н., Русинов М.А. и др. Эпидемиологическое исследование острых лейкозов в пяти регионах Российской Федерации. Гематология и трансфузиология. 2017;62(1):46–51. doi: 10.18821/0234-5730-2017-62-1-46-51.
    [Akhmerzaeva ZKh, Parovichnikova EN, Rusinov MA, et al. The epidemiological study of acute leukemia in five regions of the Russian Federation. Gematologiya i transfuziologiya. 2017;62(1):46–51. doi: 10.18821/0234-5730-2017-62-1-46-51. (In Russ)]
  34. Лукина К.А., Зайцев Д.А., Гармаева Т.Ц., Менделеева Л.П. Телемедицина как инструмент межрегионального дистанционного взаимодействия с профильными медицинскими организациями субъектов Российской Федерации: 5-летний опыт ФГБУ «НМИЦ гематологии» Минздрава России. Врач и информационные технологии. 2020;4:68–77. doi: 10.37690/1811-0193-2020-4-68-77.
    [Lukina KA, Zaytsev DA, Garmaeva TT, Mendeleeva LP. Telemedicine as a tool for remote interaction with regional hospitals: 5-year experience of the National Research Center for Hematology. Vrach i informatsionnye tekhnologii, 2020;4:68–77. doi: 10.37690/1811-0193-2020-4-68-77. (In Russ)]
  35. Железнякова И.А., Серяпина Ю.В., Михайлов И.А. и др. Методологические подходы к внедрению системы контроля качества медицинской помощи в медицинских организациях. Медицинские технологии. Оценка и выбор. 2020;42(4):13–20. doi: 10.17116/medtech
    [Zheleznyakova IA, Seryapina YuV, Mikhailov IA, et al. Methodological approaches to the development of medical care quality control at medical organizations. Medical Technologies. Assessment and Choice. 2020;42(4):13–20. doi: 10.17116/medtech20204204113. (In Russ)]
  36. Брескина Т.Н. Карта экспертизы качества медицинской помощи как основа организации контроля качества медицинской помощи в многопрофильном стационаре. Вестник Росздравнадзора. 2016;1:21–31.
    [Breskina TN. Medical quality evaluation card as a basis for medical care quality control at a multidisciplinary hospital. Vestnik Roszdravnadzora. 2016;1:21–31. (In Russ)]
  37. Сухоруких О.А., Лукьянцева Д.В., Омельяновский В.В. Критерии оценки качества медицинской помощи. Менеджмент качества в медицине. 2018;2:15–21.
    [Sukhorukikh OA, Lukyantseva DV, Omelyanovskii VV. Criteria for quality assessment of medical care. Menedzhment kachestva v meditsine. 2018;2:15–21. (In Russ)]
  38. Семочкин С.В., Толстых Т.Н., Архипова Н.В. и др. Клинико-эпидемиологическая характеристика острых миелоидных лейкозов у взрослых по данным муниципальных отделений гематологии Москвы. Терапевтический архив. 2015;87(7):26–32. doi: 10.17116/terarkh201587726-32.
    [Semochkin SV, Tolstykh TN, Arkhipova NV, et al. Clinical and epidemiological characteristics of acute myeloid leukemias in adults according to the data of the municipal hematology departments of Moscow. Terapevticheskii arkhiv. 2015;87(7):26–32. doi: 10.17116/terarkh201587726-32. (In Russ)]
  39. Лазарева О.В., Куликов С.М., Чабаева Ю.А. и др. Единая информационная система (ЕИС) «Гематология» — учет, регистрация и мониторинг пациентов с заболеваниями системы крови в РФ. Гематология и трансфузиология. 2020;65(S1):33.
    [Lazareva OV, Kulikov SM, Chabaeva YuA, et al. Unified information system (UIE) “Hematology”: administration, registration, and monitoring of patients with hematological diseases in the Russian Federation. Gematologiya i transfuziologiya, 2020;65(S1):33. (In Russ)]
  40. Куликов С.М., ГармаеваТ.Ц., Русинов М.А., Паровичникова Е.Н. Понятия, принципы и задачи популяционной гематологии. Клиническая онкогематология. 2017;10(2):250–7. doi: 10.21320/2500-2139-2017-10-2-250-257.
    [Kulikov SM, Garmaeva TTs, Rusinov MA, Parovichnikova EN. Concept, Principles, and Objectives of Population Hematology. Clinical oncohematology. 2017;10(2):250–7. doi: 10.21320/2500-2139-2017-10-2-250-257. (In Russ)]
  41. Куликов С.М., Чабаева Ю.А., Лазарева О.В. Цель создания новой национальной системы кодирования заболеваний системы крови. Гематология и трансфузиология. 2020;65(S1):32–3.
    [Kulikov SM, Chabaeva YuA, Lazareva OV. The purpose of creating a new national coding system for hematological diseases. Gematologiya i transfuziologiya. 2020;65(S1):32–3. (In Russ)]
  42. Баженов А.В., Галстян Г.М., Паровичникова Е.Н. и др. Роль интенсивной терапии в лечении больных острыми миелоидными лейкозами. Терапевтический архив. 2019;91(7):14–24. doi: 10.26442/00403660.2019.07.000321.
    [Bazhenov AV, Galstyan GM, Parovichnikova EN, et al. Role of the intensive care in treatment of patients with acute myeloid leukemia. Terapevticheskii arkhiv. 2019;91(7):14–24. doi: 10.26442/00403660.2019.07.000321. (In Russ)]
  43. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. Национальные клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых. Гематология и трансфузиология. 2014;59(1-S2):2–29.
    [Savchenko VG, Parovichnikova EN, Afanasyev BV. National clinical guidelines for the diagnosis and treatment of acute myeloid leukemia in adults. Gematologiya i transfuziologiya. 2014;59(1-S2):2–29. (In Russ)]
  44. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. Клинические рекомендации российских экспертов по лечению больных острыми миелоидными лейкозами в возрасте моложе 60 лет. Терапевтический архив. 2014;86(7):4–13.
    [Savchenko VG, Parovichnikova EN, Afanasyev BV. Clinical guidelines of Russian experts for the treatment of acute myeloid leukemia patients less than 60 years of age. Terapevticheskii arkhiv. 2014;86(7):4–13. (In Russ)]
  45. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. Клинические рекомендации по диагностике и лечению острых лимфобластных лейкозов взрослых (редакция 2018 г.) Гематология и трансфузиология. 2018;63(1-S2):5–52.
    [Savchenko VG, Parovichnikova EN, Afanasyev BV. Clinical guidelines for the diagnosis and treatment of acute lymphoblastic leukemia in adults (edition 2018). Gematologiya i transfuziologiya. 2018;63(1-S2):5–52. (In Russ)]
  46. Приказ Минздрава России от 15 ноября 2012 г. № 930н «Об утверждении Порядка оказания медицинской помощи населению по профилю «гематология»». [Decree No. 930n of the Ministry of Health of the Russian Federation dated November 15, 2012. On the approval of medical care provision in the field of hematology. (In Russ)]

Treatment Opportunities in Relapsed Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphomas (Resolution of Expert Panel)

AUTOIMMUNE THROMBOCYTOPENIA

28 июня 2021 г. в дистанционном режиме состоялся междисциплинарный совет экспертов по проблемам терапии рецидивов лимфомы Ходжкина (ЛХ) и неходжкинских лимфом (НХЛ), проведенный в целях адаптации текущих подходов к лечению этих заболеваний.

Совет прошел под председательством экспертов: профессора Норберта Шмитца, главного врача департамента гематологии, онкологии и трансплантации гемопоэтических стволовых клеток в Центре гематологии и онкологии клиники St. Georg (Гамбург, Германия), д-ра мед. наук, заведующего отделением интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационарами Евгения Евгеньевича Звонкова и д-ра мед. наук, ведущего научного сотрудника отделения высокодозной химиотерапии лимфом Аминат Умарасхабовны Магомедовой ФГБУ «НМИЦ гематологии» Минздрава России (Москва). В мероприятии также приняли участие ведущие специалисты федеральных и региональных центров гематологии и онкологии России.

Участники совета экспертов:

Норберт Шмитц (Германия), Евгений Евгеньевич Звонков (Москва), Аминат Умарасхабовна Магомедова (Москва), Наталья Александровна Фалалеева (Обнинск), Алена Юрьевна Терехова (Обнинск), Татьяна Семеновна Константинова (Екатеринбург), Ридван Казимович Ильясов (Симферополь), Татьяна Владимировна Шелехова (Саратов), Татьяна Михайловна Сычева (Астрахань), Марина Михайловна Чукавина (Коломна), Валерий Альбертович Лапин (Ярославль), Александр Абрамович Мясников (Петрозаводск), Татьяна Юрьевна Клиточенко (Волгоград), Андрей Владимирович Губкин (Москва).

В ходе работы совета экспертов были рассмотрены данные по эффективности и безопасности применения кармустина у пациентов с рецидивами ЛХ и НХЛ. Эксперты представили на обсуждение результаты собственных научных работ и наблюдений, а также поделились обширными данными международных клинических исследований.

Кармустин (БиКНУ) представляет собой производное нитрозомочевины с алкилирующим механизмом действия. Основным показанием для применения кармустина в монотерапии являются опухоли головного мозга (глиобластомы, глиомы ствола мозга, эпендимомы, астроцитомы, метастазы рака). В составе комбинированной лекарственной терапии кармустин применяется в противорецидивных режимах и схемах кондиционирования для лечения лимфом и множественной миеломы. В монотерапии препарат применяется при опухолях головного мозга (глиобластомы, глиомы ствола мозга, эпендимомы, астроцитомы, метастазы злокачественных новообразований).

Кармустин вызывает цитотоксические эффекты вследствие переноса своих алкильных групп на различные биомолекулы. Алкилирование ядерной ДНК является наиболее важным звеном в механизме действия препарата и приводит к гибели клетки. Помимо этого некоторые метаболиты кармустина обладают способностью подавлять активность ферментов окислительного фосфорилирования, энергообеспечение синтетических процессов и митоз.

Вторым механизмом действия кармустина является карбамоилирование лизиновых остатков белков через образование изоцианатов (возникают разрывы в молекуле ДНК, образуются внутри- и межмолекулярные сшивки цепей и нарушается синтез ДНК).

Кармустин относится к циклонеспецифичным препаратам. По данным большинства исследований, препарат не обладает перекрестной устойчивостью с другими алкилирующими агентами, хотя и встречаются единичные сообщения о возможной перекрестной рефрактерности с ломустином.

В рамках дискуссии были обозначены группы пациентов, которым показана терапия с использованием кармустинсодержащих режимов.

По результатам обсуждения перечисленных выше данных совет экспертов заключил:

  1. В связи со сменой производителя и затянувшимся процессом перерегистрации препарата применение кармустина (БиКНУ) в Российской Федерации было прервано. В условиях отсутствия препарата предпринимались попытки разработать альтернативные программы высокодозной химиотерапии. К настоящему времени возобновлены регулярные и непрерывные поставки кармустина (БиКНУ) на территорию РФ, что позволяет применять его в составе различных схем противоопухолевой лекарственной терапии.
  2. Несмотря на существование альтернативных схем терапии, рандомизированные исследования по сравнению их эффективности с кармустинсодержащими режимами ограничены и их недостаточно для выбора оптимальной схемы.
  3. Программа BEAM является оптимальным режимом кондиционирования для больных ЛХ и НХЛ. Она позволяет достичь до 70 % полных ремиссий при рецидивах и рефрактерных формах ЛХ и до 50 % — при рецидивах и рефрактерных формах НХЛ.
  4. Применение кармустина оправдано в составе схем лекарственной противорецидивной терапии у больных НХЛ. Режимы dexa-BEAM и mini-BEAM являются эффективными в индукционной химиотерапии рецидивов лимфом, признанными на международном уровне.
  5. В соответствии с клиническими рекомендациями по лечению злокачественных лимфопролиферативных заболеваний кармустин (БиКНУ) рекомендуется пациентам с рецидивами ЛХ, диффузной В-крупноклеточной лимфомы, первичной медиастинальной (тимической) В-крупноклеточной лимфомы, лимфомы Беркитта, нодальных Т-клеточных лимфом, лимфомы из клеток мантии.
  6. Переносимость кармустинсодержащих режимов приемлемая и сопоставима с уровнем переносимости ломустин- и бендамустинсодержащих режимов.

Участники совета экспертов пришли к единодушному заключению, что возобновление применения кармустина в схемах лечения злокачественных лимфопролиферативных заболеваний позволит значительно улучшить показатели выживаемости пациентов, у которых не могут быть применены иные схемы терапии, уменьшить смертность от основного заболевания и осложнений, а также оптимизировать финансовые затраты на ведение этой категории больных.

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Low-Risk Myelodysplastic Syndromes

AUTOIMMUNE THROMBOCYTOPENIA

SV Gritsaev

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

For correspondence: Sergei Vasilevich Gritsaev, MD, PhD, Head of Republican Center for Bone Marrow Transplantation, Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: gritsaevsv@mail.ru

Interview conducted by Prof. E.A. Osmanov, MD, PhD.

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