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

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 %; p = 0.052). The maintenance treatment prolonged the median cumulative relapse risk from 1.2 to 2.1 years (p = 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 (p = 0.004), baseline leukocytosis ³ 50 000/ml (p = 0.035) and secondary AML (p = 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 %; p < 0.001), thrombocytopenia (100 vs 55.2 %; p = 0.012), and enteropathy (29.4 vs 0 %; p = 0.001).

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

• S.V. Semochkin 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; N.I. Pirogov Russian National Research Medical University under the Ministry of Health of the Russian Federation, 1 Ostrovityanova str., Moscow, Russian Federation, 117997 ; ФГБУ «ФНКЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» МЗ РФ, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997; ГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» МЗ РФ, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997
• T.N. Tolstykh 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 ; ФГБУ «ФНКЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» МЗ РФ, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997
• V.V. Lunin S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• N.K. Khuazheva S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• A.I. Kostin S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• S.A. Chernysh S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• M.E. Pochtar S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• V.L. Ivanova S.P. Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Городская клиническая больница им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284

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