Rationale for Maintenance Treatment of Patients with Acute Myeloid Leukemia below 65 Years of Age, According to Data of a Retrospective Analysis of Protocols AML-2000 and AML-2007

S.V. Semochkin1,2, T.N. Tolstykh1, V.V. Lunin3, N.K. Khuazheva3, A.I. Kostin3, S.A. Chernysh3, M.E. Pochtar’3, V.L. Ivanova3

1 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117997

2 N.I. Pirogov Russian National Research Medical University under the Ministry of Health of the Russian Federation, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

3 S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284

For correspondence: S.V. Semochkin, DSci, Professor, 1 Samory Mashela str., Moscow, Russian Federation, 117997; Tel: +7(495)653-14-78; e-mail: semochkin_sv@rsmu.ru

For citation: Semochkin S.V., Tolstykh T.N., Lunin V.V., Khuazheva N.K., Kostin A.I., Chernysh S.A., Pochtar’ M.E., Ivanova V.L. Rationale for Maintenance Treatment of Patients with Acute Myeloid Leukemia below 65 Years of Age According to Data of a Retrospective Analysis of Protocols AML-2000 and AML-200. Klin. Onkogematol. 2014; 7(4): 564–572 (In Russ.).


Objective. To evaluate the efficacy of prolonged maintenance therapy versus intensified consolidation for patients with acute myeloid leukemia (AML).

Patients and methods. 198 patients with median age 43.9 years (ranging from 15 to 64) with newly diagnosed AML were enrolled in this retrospective study. Over the period from 2000 to 2009, 97 patients were assigned to receive treatment in accordance with Protocol AML-2000 which provided 2 cycles of induction according to the «7+3» scheme (the dose of daunorubicin is 45 mg/m2), 3 cycles of consolidation according to the «5+1» scheme, and 2-year maintenance treatment consisting of the same cycles. 101 patients were enrolled in the subsequent study according to Protocol AML-2007; over the period from 2007 to 2012, they received 2 cycles of induction «7+3» or «7+3» plus HAM, if the complete remission (CR) was not achieved after the first cycle. Then there were 4 cycles of treatment with high-dose cytarabine without subsequent maintenance treatment.

Results. In total, 57.1 % of patients achieved CR. 2-year overall survival (OS) was higher for Protocol AML-2000 (39.2 ± 5.0 vs 28.5 ± 4.8 %; = 0.052). The maintenance treatment prolonged the median cumulative relapse risk from 1.2 to 2.1 years (= 0.008). However no statistically significant difference was observed for the 5-year relapse-free survival and OS between the two trials with the median follow-up for surviving patients equal to 3.3 and 9.9 years, respectively. Age ³ 46 years (= 0.004), baseline leukocytosis ³ 50 000/ml (= 0.035) and secondary AML (= 0.020) had a negative prognostic effect on the 5-year OS. Intensive consolidation according to Protocol AML-2007 was associated with higher incidence of III/IV degree adverse events, including neutropenia (100 vs 68.9 %; < 0.001), thrombocytopenia (100 vs 55.2 %; = 0.012), and enteropathy (29.4 vs 0 %; = 0.001).

Conclusion. The maintenance treatment is an effective therapeutic option for AML, since it prolongs the median cumulative relapse risk.

Keywords: acute myeloid leukemia, maintenance treatment.

Accepted: September 19, 2014

Read in PDF (RUS)pdficon


  1. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Нацио- нальные клинические рекомендации по диагностике и лечению острых миелоидных лейкозов у взрослых. Гематология и трансфузиология. 2014; 59(1, прил. 2): 1–29. [Savchenko V.G., Parovichnikova E.N., Afanas’ev B.V. et al. National clinical recommendations for diagnosing and treatment of acute myeloid leukemia in adults. Gematologiya i transfuziologiya. 2014; 59(1, suppl. 2): 1–29. (In Russ.)]
  2. Recher C., Bene M.C., Lioure B. et al. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia. Leukemia. 2014; 28(2): 440–3.
  3. Teuffel O., Leibundgut K., Lehrnbecher T. et al. Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and metaanalysis. Br. J. Haematol. 2013; 161(2): 192–203.
  4. Willemze R., Suciu S., Meloni G. et al. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J. Clin. Oncol. 2014; 32(3): 219–28.
  5. Milligan D.W., Grimwade D., Cullis J.O. et al. Guidelines on the management of acute myeloid leukaemia in adults. Br. J. Haematol. 2006; 135(4): 450–74.
  6. Bloomfield C.D., Lawrence D., Byrd J.C. et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res. 1998; 58(18): 4173–9.
  7. Бондаренко С.Н., Семенова Е.В., Вавилов В.Н. и др. Аллогенная транс- плантация гемопоэтических стволовых клеток при остром миелобластном лейкозе в первой ремиссии. Терапевтический архив. 2013; 85(7): 18–25. [Bondarenko S.N., Semenova E.V., Vavilov V.N. et al. Allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia in the first remission. Terapevticheskii arkhiv. 2013; 85(7): 18–25. (In Russ.)]
  8. Baer M.R. Is there a role for maintenance therapy in acute myeloid leukaemia? Best Pract. Res. Clin. Haematol. 2009; 22(4): 517–21.
  9. Dohner H., Estey E.H., Amadori S. et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010; 115(3): 453–74.
  10. Buchner T., Krug U., Berdel W.E. et al. Maintenance for acute myeloid leukemia revisited. Curr. Treat. Options Oncol. 2007; 8(4): 296–304.
  11. Bennett J.M., Catovsky D., Daniel M.T. et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-AmericanBritish Cooperative Group. Ann. Intern. Med. 1985; 103(4): 620–5.
  12. Swerdlow S.H., Campo E., Harris N.L. et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Fourth edition. Lyon: IARC Press, 2008.
  13. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Published May 28, 2009.
  14. Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations. J. Am. Statis. Assn. 1958; 53(282): 457–81.
  15. Prentice R.L., Kalbfleisch J.D. Mixed discrete and continuous Cox regression model. Lifetime Data Anal. 2003; 9(2): 195–210.
  16. Berty H.P., Shi H., Lyons-Weiler J. Determining the statistical significance of survivorship prediction models. J. Eval. Clin. Pract. 2010; 16(1): 155–65.
  17. Kantarjian H., O’Brien S. Questions regarding frontline therapy of acute myeloid leukemia. Cancer. 2010; 116(21): 4896–901.
  18. Reese N.D., Schiller G.J. High-dose cytarabine (HD araC) in the treatment of leukemias: a review. Curr. Hematol. Malig. Rep. 2013; 8(2): 141–8.
  19. Баранова О.Ю., Волкова М.А., Френкель М.А. и др. Анализ резуль- татов различных программ терапии острых нелимфобластных лейкозов МО-М2, М4-М7 ФАБ-вариантами (по данным РОНЦ им. Н.Н. Блохина РАМН). Гематология и трансфузиология. 2003; 48(2): 3–10. [Baranova O.Yu., Volkova M.A., Frenkel’ M.A. et al. Analysis of results of different treatment programs for acute nonlymphoblastic leukemias with MOM2, M4-M7 FAB variants (According to data of N.N. Blokhin Cancer Research Center of RAMS). Gematologiya i transfuziologiya. 2003; 48(2): 3–10. (In Russ.)]
  20. Buchner T., Urbanitz D., Hiddemann W. et al. Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. J. Clin. Oncol. 1985; 3(12): 1583–9.
  21. Buchner T., Hiddemann W., Berdel W.E. et al. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group. J. Clin. Oncol. 2003; 21(24): 4496–504.
  22. Грицаев С.В., Мартынкевич И.С., Запреева И.М. и др. Эффектив- ность первого и повторного курсов индукционной терапии больных de novo острым миелоидным лейкозом. Бюллетень Сибирского отделения Российской академии медицинских наук. 2013; 33(1): 67–75. [Gritsaev S.V., Martynkevich I.S., Zapreeva I.M. et al. Effectiveness of the first and repeated courses of induction therapy of patients with de novo diagnosed acute myeloid leukemia. Byulleten’ Sibirskogo otdeleniya Rossiiskoi akademii meditsinskikh nauk. 2013; 33(1): 67–75. (In Russ.)]
  23. Zhu H.H., Liu Y.R., Jiang H. et al. CD34 expression on bone marrow blasts is a novel predictor of poor prognosis independent of FLT3-ITD in acute myeloid leukemia with the NPM1-mutation. Leuk. Res. 2013; 37(6): 624–30.
  24. Repp R., Schaekel U., Helm G. et al. Immunophenotyping is an independent factor for risk stratification in AML. Cytometry B Clin. Cytom. 2003; 53(1): 11–9.
  25. Паровичникова Е.Н., Клясова Г.А., Соколов А.Н. и др. Первые ре- зультаты лечения острых миелоидных лейкозов взрослых по протоколу ОМЛ-01.10 научно-исследовательской группы гематологических центров России. Терапевтический архив. 2012; 84(7): 10–15. [Parovichnikova E.N., Klyasova G.A., Sokolov A.N. et al. First results of treatement of adults with acute myeloid leukemia according to protocol OML-01.10 of the scientific research group of hematological centers of Russia. Terapevticheskii arkhiv. 2012; 84(7): 10–15. (In Russ.)]