Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation

Abstract

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

Development of program therapy for patients with acute myeloid leukemia under the age of 60 years, based on the principles of differentiated effects

“…В классификации Всемирной организации здравоохранения опухолей миелоидной природы выделены ОМЛ/ исМДС. У больных этой группы долгосрочный прогноз заболевания крайне неблагоприятный, особенно это касается [10]. Другой вариант терапии у больных ОМЛ/исМДС рассматривается и в рекомендациях NCCN-2.2020.…”

The role of interleukin-3 and its receptor in acute leukemia pathogenesis

“…Хромосомные аберрации и молекулярные аномалии, определяющие неблагоприятный прогноз и неудовлетворительные результаты терапии, требуют дифференцированного подхода к лечению больных ОМЛ. Такие аномалии кариотипа, как inv16 и t (8;21), ассоциированы с благоприятным прогнозом и 60-65 % 5-летней общей выживаемости, а присутствие комплексного или моносомного кариотипа, аномалии хромосом 5, 7 и inv3 ассоциируется с неблагоприятным течением ОМЛ, при котором 5-летняя общая выживаемость составляет 20-25 % [2,3]. В 30 % случаев у больных ОМЛ с нормальным кариотипом обнаруживают мутацию FLT3-ITD (fms-related tyrosine kinase 3internal tandem duplication), при которой происходят внутренние тандемные повторы в гене тирозинкиназы FLT3.…”