zdorПроблемы здоровья и экологииHealth and Ecology Issues2220-09672708-6011Gomel State Medical University10.51523/2708-6011.2014-11-4-15zdor-1555Research ArticleКЛИНИЧЕСКАЯ МЕДИЦИНАCLINICAL MEDICINEЛЕЧЕНИЕ РЕЦИДИВОВ И РЕФРАКТЕРНЫХ ФОРМ ОСТРЫХ МИЕЛОИДНЫХ ЛЕЙКОЗОВTHE TREATMENT FOR RELAPSED AND REFRACTORY FORMS OF ACUTE MYELOID LEUKEMIAСуворовД. И.SuvorovD. I.noemail@neicon.ruКлимковичН. Н.KlimkovichN. N.noemail@neicon.ruРеспубликанский научно-практический центр радиационной медицины и экологии человека, г. Гомель Белорусская медицинская академия последипломного образования, г. МинскRepublican Research Centre for Radiation Medicine and Human Ecology, Gomel Belarusian Medical Academy of Post-Graduate Education, Minsk201428122014047580Copyright © Суворов Д.И., Климкович Н.Н., 20142014Суворов Д.И., Климкович Н.Н.Suvorov D.I., Klimkovich N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.gsmu.by/jour/article/view/1555

Обзор посвящен рецидивам и рефрактерным формам острых миелоидных лейкозов, которые являются гетерогенными заболеваниями и не имеют универсальной единой терапевтической схемы. В статье дана характеристика протоколов с включением новых агентов, показана роль аллогенной трансплантации гемопоэтических стволовых клеток, систематизированы достижения в стратификации риска для лечения острых миелоидных лейкозов. Определена перспектива персонализации терапии с учетом молекулярных тестов. Показано гарантированное снижение частоты рецидивов при использовании более эффективных индукционных и постремиссионных протоколов.

The review focuses on relapse and refractory forms of acute myeloid leukemia, which is a heterogeneous disease and does not have a single universal therapeutic scheme. The paper presents the characteristics of protocols with inclusion of new agents, shows the role of allogenic hematopoietic stem cell transplantation and advances in risk stratification for the treatment for acute myeloid leukemia. The prospects of the therapy personalization based on molecular tests have been determined. The application of more effective induction and post-remission protocols shows a guaranteed reduction in the relapse rate.

острый миелоидный лейкозрецидиврефрактерная формалечениеacute myeloid leukemiarelapserefractory formtreatmentReferencesForman, S. J. The myth of the second remission of acute leukemia in the adult / S. J. Forman, J. M. Rowe // Blood. - 2013. - Vol. 121(7). - P. 1077-1082.Forman, S. J. The myth of the second remission of acute leukemia in the adult / S. J. Forman, J. M. Rowe // Blood. - 2013. - Vol. 121(7). - P. 1077-1082.Ofran, Y. Treatment for relapsed acute myeloid leukemia: what is new? / Y. Ofran, J. M. Rowe // Curr Opin Hematol. - 2012. - Vol. 19. - P. 89-94.Ofran, Y. Treatment for relapsed acute myeloid leukemia: what is new? / Y. Ofran, J. M. Rowe // Curr Opin Hematol. - 2012. - Vol. 19. - P. 89-94.The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups / C. Schoch [et al.] // Haematologica. - 2004. - Vol. 89(9). - P. 1082-1090.The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups / C. Schoch [et al.] // Haematologica. - 2004. - Vol. 89(9). - P. 1082-1090.Estey, E. H. Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management / E. H. Estey // Am J Hematol. - 2012. - Vol. 87(1). - P. 89-99.Estey, E. H. Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management / E. H. Estey // Am J Hematol. - 2012. - Vol. 87(1). - P. 89-99.The European Leukemia Net AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach / J. Cornelissen [et al.] // Nat Rev Clin Oncol. - 2012. - Vol. 9(10). - P. 579-590.The European Leukemia Net AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach / J. Cornelissen [et al.] // Nat Rev Clin Oncol. - 2012. - Vol. 9(10). - P. 579-590.Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse / S. Kurosawa [et al.] // Haematologica. - 2010. - Vol. 95. - P. 1857-1864.Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse / S. Kurosawa [et al.] // Haematologica. - 2010. - Vol. 95. - P. 1857-1864.A new Leukemia Prognostic Scoring System for refractory/ relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study / P. Chevallier [et al.] // Leukemia. - 2011. - Vol. 25. - P. 939-944.A new Leukemia Prognostic Scoring System for refractory/ relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study / P. Chevallier [et al.] // Leukemia. - 2011. - Vol. 25. - P. 939-944.Juliusson, G. Most 70- to 79-year-old patients with acute myeloid leukemia do benefit from intensive treatment / G. Juliusson // Blood. - 2011. - Vol. 117. - P. 3473-3474.Juliusson, G. Most 70- to 79-year-old patients with acute myeloid leukemia do benefit from intensive treatment / G. Juliusson // Blood. - 2011. - Vol. 117. - P. 3473-3474.Rowe, J. M. How I treat acute myeloid leukemia / J. M. Rowe, M.S. Tallman // Blood. - 2010. - Vol. 116. - P. 3147-3156.Rowe, J. M. How I treat acute myeloid leukemia / J. M. Rowe, M.S. Tallman // Blood. - 2010. - Vol. 116. - P. 3147-3156.Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group / M. R. Litzow [et al.] // Br J. Haematol. - 2010. - Vol. 148. - P. 217-225.Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group / M. R. Litzow [et al.] // Br J. Haematol. - 2010. - Vol. 148. - P. 217-225.Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure / M. Duval [et al.] // J. Clin. Oncol. - 2010. - Vol. 28. - P. 3730-3738.Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure / M. Duval [et al.] // J. Clin. Oncol. - 2010. - Vol. 28. - P. 3730-3738.Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation / C. Schmid [et al.] // Blood. - 2006. - Vol. 108. - P. 1092-1099.Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation / C. Schmid [et al.] // Blood. - 2006. - Vol. 108. - P. 1092-1099.A phase II trial of sequential treatment with cytoreductive therapy and reduced intensity conditioning allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukaemia, high-risk MDS and other high risk myeoid malignancies: an interim report / D. A. Tsitsikas [et al.] // Blood. - 2010. - Vol. 116. - P. 3480a.A phase II trial of sequential treatment with cytoreductive therapy and reduced intensity conditioning allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukaemia, high-risk MDS and other high risk myeoid malignancies: an interim report / D. A. Tsitsikas [et al.] // Blood. - 2010. - Vol. 116. - P. 3480a.Alternative donors hematopoietic stem cells transplantation for adults with acute myeloid leukemia: umbilical cord blood or haploidentical donors? / A. Ruggeri [et al.] // Best Pract Res Clin Haematol. - 2010. - Vol. 23. - P. 207-216.Alternative donors hematopoietic stem cells transplantation for adults with acute myeloid leukemia: umbilical cord blood or haploidentical donors? / A. Ruggeri [et al.] // Best Pract Res Clin Haematol. - 2010. - Vol. 23. - P. 207-216.Auto-SCT for AML in second remission: CALGB study 9620 / C. A. Linker [et al.] // Bone Marrow Transplant. - 2009. - Vol. 44. - P. 353-359.Auto-SCT for AML in second remission: CALGB study 9620 / C. A. Linker [et al.] // Bone Marrow Transplant. - 2009. - Vol. 44. - P. 353-359.European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy / A. K. Burnett [et al.] // J Clin Oncol. - 2010. - Vol. 28. - P. 2389-2395.European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy / A. K. Burnett [et al.] // J Clin Oncol. - 2010. - Vol. 28. - P. 2389-2395.Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukemia / P. S. Becker [et al.] // Br J Haematol. - 2011. - Vol. 155. - P. 182-189.Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukemia / P. S. Becker [et al.] // Br J Haematol. - 2011. - Vol. 155. - P. 182-189.Faderl, S. Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia / S. Faderl, V. Gandhi, H. M. Kantarjian // Curr Opin Hematol. - 2008. - Vol. 15. - P. 101-107.Faderl, S. Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia / S. Faderl, V. Gandhi, H. M. Kantarjian // Curr Opin Hematol. - 2008. - Vol. 15. - P. 101-107.Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse / M. Levis [et al.] // Blood. - 2011. - Vol. 117. - P. 3294-3301.Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse / M. Levis [et al.] // Blood. - 2011. - Vol. 117. - P. 3294-3301.Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib / M. Sharma [et al.] // Biol Blood Marrow Transplant. - 2011. - Vol. 17. - P. 1874-1877.Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib / M. Sharma [et al.] // Biol Blood Marrow Transplant. - 2011. - Vol. 17. - P. 1874-1877.A phase II open-label, AC220 monotherapy efficacy (ACE) study in patients with acute myeloid leukemia (AML) with FLT3-ITD activating mutations: interim results / J. Cortes [et al.] // Haematologica. - 2011. - Vol. 96. - P. 1019a.A phase II open-label, AC220 monotherapy efficacy (ACE) study in patients with acute myeloid leukemia (AML) with FLT3-ITD activating mutations: interim results / J. Cortes [et al.] // Haematologica. - 2011. - Vol. 96. - P. 1019a.Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukemia / C. C. Smith [et al.] // Nature. - 2012. - Vol. 485. - P. 260-263.Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukemia / C. C. Smith [et al.] // Nature. - 2012. - Vol. 485. - P. 260-263.Identification of predictive markers of cytarabine response in AML by integrative analysis of gene-expression profiles with multiple phenotypes / J. K. Lamba [et al.] // Pharmacogenomics. - 2011. - Vol. 12. - P. 327-339.Identification of predictive markers of cytarabine response in AML by integrative analysis of gene-expression profiles with multiple phenotypes / J. K. Lamba [et al.] // Pharmacogenomics. - 2011. - Vol. 12. - P. 327-339.A phase Ib study combining the mTOR inhibitor everolimus (RAD001) with low-dose cytarabine in untreated elderly AML / A. H. Wei [et al.] // Blood. - 2010. - Vol. 116. - P. 3299a.A phase Ib study combining the mTOR inhibitor everolimus (RAD001) with low-dose cytarabine in untreated elderly AML / A. H. Wei [et al.] // Blood. - 2010. - Vol. 116. - P. 3299a.Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia / P. Fenaux [et al.] // J. Clin. Oncol. - 2010. - Vol. 28. - P. 562-569.Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia / P. Fenaux [et al.] // J. Clin. Oncol. - 2010. - Vol. 28. - P. 562-569.-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis / A. Czibere [et al.] // Bone Marrow Transplant. - 2010. - Vol. 45. - P. 872-876.-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis / A. Czibere [et al.] // Bone Marrow Transplant. - 2010. - Vol. 45. - P. 872-876.Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial / U. Platzbecker [et al.] // Leukemia. - 2012. - Vol. 26(3). - P. 381-389.Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial / U. Platzbecker [et al.] // Leukemia. - 2012. - Vol. 26(3). - P. 381-389.Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia / A. D. Schimmer [et al.] // J. Clin. Oncol. - 2009. - Vol. 27. - P. 4741-4746.Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia / A. D. Schimmer [et al.] // J. Clin. Oncol. - 2009. - Vol. 27. - P. 4741-4746.Katragadda, L. XIAP antisense therapy with AEG 35156 in acute myeloid leukemia / L. Katragadda, B. Z. Carter, G. Borthakur // Expert Opin Investig Drugs. - 2013. - Vol. 22(5). - P. 663-670.Katragadda, L. XIAP antisense therapy with AEG 35156 in acute myeloid leukemia / L. Katragadda, B. Z. Carter, G. Borthakur // Expert Opin Investig Drugs. - 2013. - Vol. 22(5). - P. 663-670.Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination / V. F. Van Tendeloo [et al.] // Proc Natl Acad Sci USA. - 2010. - Vol. 107. - P. 13824-13829.Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination / V. F. Van Tendeloo [et al.] // Proc Natl Acad Sci USA. - 2010. - Vol. 107. - P. 13824-13829.Lin, Ch. The role of peptide and DNA vaccines in myeloid leukemia immunotherapy / Ch. Lin, Y. Li //Cancer Cell International. - 2013. - Vol. 13. - 7 p.Lin, Ch. The role of peptide and DNA vaccines in myeloid leukemia immunotherapy / Ch. Lin, Y. Li //Cancer Cell International. - 2013. - Vol. 13. - 7 p.Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients / M. Guo [et al.] // Blood. - 2011. - Vol. 117. -P. 936-941.Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients / M. Guo [et al.] // Blood. - 2011. - Vol. 117. -P. 936-941.

The authors declare that there are no conflicts of interest present.