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

Elena N. Parovichnikova; Паровичникова Елена Николаевна; Irina A. Lukianova; Лукьянова Ирина Анатольевна; Vera V. Troitskaya; Троицкая Вера Витальевна; Mikhail Yu. Drokov; Дроков Михаил Юрьевич; Larisa A. Kuzmina; Кузьмина Лариса Анатольевна; Andrei N. Sokolov; Соколов Андрей Николаевич; Alina V. Kokhno; Кохно Алина Владимировна; Zalina T. Fidarova; Фидарова Залина Таймуразовна; Irina V. Galtseva; Гальцева Ирина Владимировна; Yuliya O. Davydova; Давыдова Юлия Олеговна; Anastasiia I. Kashlakova; Кашлакова Анастасия Игоревна; Elena O. Gribanova; Грибанова Елена Олеговна; Eugene E. Zvonkov; Звонков Евгений Евгеньевич; Elena P. Sysoeva; Сысоева Елена Павловна; Valentina N. Dvirnyk; Двирнык Валентина Николаевна; Tatiana N. Obukhova; Обухова Татьяна Никифоровна; Andrei B. Sudarikov; Судариков Андрей Борисович; Yuliya V. Sidorova; Сидорова Юлия Владимировна; Sergei M. Kulikov; Куликов Сергей Михайлович; Yuliia A. Chabaeva; Чабаева Юлия Александровна; Valerii G. Savchenko; Савченко Валерий Григорьевич

doi:10.26442/00403660.2021.07.200946

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

Authors: Parovichnikova E.N.¹, Lukianova I.A.¹, Troitskaya V.V.¹, Drokov M.Y.¹, Kuzmina L.A.¹, Sokolov A.N.¹, Kokhno A.V.¹, Fidarova Z.T.¹, Galtseva I.V.¹, Davydova Y.O.¹, Kashlakova A.I.¹, Gribanova E.O.¹, Zvonkov E.E.¹, Sysoeva E.P.¹, Dvirnyk V.N.¹, Obukhova T.N.¹, Sudarikov A.B.¹, Sidorova Y.V.¹, Kulikov S.M.¹, Chabaeva Y.A.¹, Savchenko V.G.¹
Affiliations:
1. National Research Center for Hematology
Issue: Vol 93, No 7 (2021)
Pages: 753-762
Section: Editorial
URL: https://journals.rcsi.science/0040-3660/article/view/76304
DOI: https://doi.org/10.26442/00403660.2021.07.200946
ID: 76304

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Abstract

Aim. To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years.

Materials and methods. The study included 89 AML patients who were aged below 60 years and received treatment within the AML-17 and mOML-17 protocols. Cytogenetic and molecular genetic studies were performed in all patients. The presence of mutations in the FLT3, NPM1, CEBPa genes was assessed by fragment analysis. 35 patients underwent a study for mutTP53, mutRUNX1 using next generation sequencing (NGS). The minimum residual population of tumor cells was evaluated by multicolor flow cytometry. Statistical analysis was performed using the procedures of the SAS 9.3 package.

Results. Complete remission (CR) was achieved in 89.7% of patients treated with intensive chemotherapy (CT) courses and in 52.4% of patients treated with low-dose CT courses. 8.8% of intensively treated patients were refractory to therapy, and 38% did not respond to low-dose exposure. The early mortality rate was 3%. The overall survival and disease-free 3-year survival for patients included in 2 consecutive studies was were 60% and 67%, respectively. The level of minimal residual disease (MRD) after the first course of induction CT was an important prognostic indicator. The three-year relapse-free survival for patients in whom CR was achieved after the first course of induction CT and in whom MRD was not detected (MRD-negative status was obtained) was 90% compared to 43% for patients who were MRD positive after the first course of induction CT (p=0.00001).

Conclusion. The key factor that significantly affects the long-term results of therapy is the rate of MRD after the first course of induction CT.

Keywords

acute myeloid leukemia, minimal residual disease, risk group, transplantation of allogeneic hematopoietic stem cells