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:
- 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
Cite item
Full Text
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.
Full Text
##article.viewOnOriginalSite##About the authors
Elena N. Parovichnikova
National Research Center for Hematology
Author for correspondence.
Email: elenap@blood.ru
ORCID iD: 0000-0001-6177-3566
д-р мед. наук, зав. отд. химиотерапии гемобластозов, депрессий кроветворения и ТКМ
Russian Federation, MoscowIrina A. Lukianova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-8337-2242
врач-гематолог отд-ния интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с дневным стационаром
Russian Federation, MoscowVera V. Troitskaya
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-4827-8947
канд. мед. наук, зам. ген. дир. по лечебной работе, зав. отд-нием интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с круглосуточным и дневным стационарами
Russian Federation, MoscowMikhail Yu. Drokov
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-9431-8316
канд. мед. наук, рук. сектора по изучению иммунных воздействий и осложнений после ТКМ, врач-гематолог
Russian Federation, MoscowLarisa A. Kuzmina
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-6201-6276
канд. мед. наук, зав. отд-нием ТКМ
Russian Federation, MoscowAndrei N. Sokolov
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0003-1494-7978
канд. мед. наук, ст. науч. сотр. отд-ния интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с круглосуточным и дневным стационарами
Russian Federation, MoscowAlina V. Kokhno
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0003-0261-5941
канд. мед. наук, нач. клинико-диагностического отд.
Russian Federation, MoscowZalina T. Fidarova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0003-0934-6094
канд. мед. наук, врач-гематолог, зав. отд-нием интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с дневным стационаром
Russian Federation, MoscowIrina V. Galtseva
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-8490-6066
канд. мед. наук, зав. научно-клинической лаб. иммунофенотипирования клеток крови и костного мозга
Russian Federation, MoscowYuliya O. Davydova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-5932-0285
канд. мед. наук, врач клинической лабораторной диагностики научно-клинической лаб. иммунофенотипирования клеток крови и костного мозга
Russian Federation, MoscowAnastasiia I. Kashlakova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-3548-8929
врач-стажер отд-ния интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с круглосуточным стационаром
Russian Federation, MoscowElena O. Gribanova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-4155-7820
канд. мед. наук, зав. отд-нием интенсивной высокодозной химиотерапии гематологических заболеваний с круглосуточным и дневным стационарами
Russian Federation, MoscowEugene E. Zvonkov
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-2639-7419
д-р мед. наук, зав. отд-нием интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационарами
Russian Federation, MoscowElena P. Sysoeva
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-5056-9540
канд. мед. наук, ст. науч. сотр., врач-гематолог отд-ния орфанных заболеваний
Russian Federation, MoscowValentina N. Dvirnyk
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-9877-0796
канд. мед. наук, зав. централизованной клинико-диагностической лаб.
Russian Federation, MoscowTatiana N. Obukhova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0003-1613-652X
канд. мед. наук, зав. лаб. кардиологии
Russian Federation, MoscowAndrei B. Sudarikov
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-9463-9187
д-р биол. наук, зав. научно-клинической лаб. молекулярной гематологии
Russian Federation, MoscowYuliya V. Sidorova
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0003-1936-0084
канд. мед. наук, ст. науч. сотр. лаб. молекулярной гематологии
Russian Federation, MoscowSergei M. Kulikov
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0002-6288-7570
канд. техн. наук, зав. информационно-аналитическим отд.
Russian Federation, MoscowYuliia A. Chabaeva
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-8044-598X
канд. техн. наук, зам. зав. информационно-аналитическим отд.
Russian Federation, MoscowValerii G. Savchenko
National Research Center for Hematology
Email: elenap@blood.ru
ORCID iD: 0000-0001-8188-5557
акад. РАН, д-р мед. наук, проф., ген. дир.
Russian Federation, MoscowReferences
- Döhner H, Estey E, Grimwade D, et al. Bloomfield. Review Article Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-48. doi: 10.1182/blood-2016-08-733196
- Pollyea DA, Bixby D, Perl A, et al. NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021. J Natl Compr Canc Netw. 2021 Jan 6;19(1):16-27. doi: 10.6004/jnccn.2021.0002.
- Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012;9(10):579-90. doi: 10.1038/nrclinonc.2012.150
- Ye XN, Zhou XP, Wei JY, et al. Epigenetic priming with decitabine followed by low-dose idarubicin/cytarabine has an increased anti-leukemic effect compared to traditional chemotherapy in high-risk myeloid neoplasms. Leuk Lymphoma. 2016;57(6):1311-8. doi: 10.3109/10428194.2015.1091931
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-240. doi: 10.1182/blood-2016-03-643544
- Anelli L, Pasciolla C, Zagaria A, et al. Monosomal karyotype in myeloid neoplasias: a literature review. Onco Targets Ther. 2017;10:2163-71. doi: 10.2147/OTT.S133937
- Brands-Nijenhuis AV, Labopin M, Schouten HC, et al. Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT. Haematologica. 2016;101(2):248-55. doi: 10.3324/haematol.2015.132654
- Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374:2209-21. doi: 10.1056/NEJMoa1516192
- Rogers HJ, Vardiman JW, Anastasi J, et al. Complex or monosomal karyotype and not blast percentageis associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99(5):821-9. doi: 10.3324/haematol.2013.096420
- Паровичникова Е.Н., Лукьянова И.А., Троицкая В.В., и др. Результаты программной терапии острых миелоидных лейкозов в ФГБУ «НМИЦ гематологии» Минздрава России. Терапевтический архив. 2018;90(7):14-22 [Parovichnikova EN, Lukianova IA, Troitskaya VV, et al. Results of program acute myeloid leukemia therapy use in National medical research center for hematology of the Ministry of Health of Russian Federation. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(7):14-22 (in Russian)]. doi: 10.26442/terarkh201890714-22
- Büchner T, Berdel WE, Schoch C, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol. 2006;24(16):2480-9. doi: 10.1200/JCO.2005.04.5013
- Baron F, Stevens-Kroef M, Kicinski M, et al. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2019;104(6):1168-75. doi: 10.3324/haematol.2018.204826
- Büchner T, Hiddemann W, Berdel WE, 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. doi: 10.1200/JCO.2003.02.133
- Schmid C, Schleuning M, Tischer J, et al. Early allo-SCT for AML with a complex aberrant karyotype – results from a prospective pilot study. Bone Marrow Transplant. 2012;47:46-53. doi: 10.1038/bmt.2011.15
- van Gelder M, de Wreede LC, Schetelig J, et al. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia. Leukemia. 2013;27(4):879-88. doi: 10.1038/leu.2012.297
- DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17. doi: 10.1182/blood-2018-08-868752
- Bazarbachi A, Bug G, Baron F, et al. Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3-internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2020;105(6):1507-16. doi: 10.3324/haematol.2019.243410