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Comparison of the treatment results in adult patients with acute Ph-negative lymphoblastic leukemia on protocols of the Russian multicenter studies ALL-2009 and ALL-2016

https://doi.org/10.35754/0234-5730-2022-67-4-460-477

Abstract

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.

Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.

Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.

Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

About the Authors

E. N. Parovichnikova
National Medical Research Center for Hematology
Russian Federation

Elena N. Parovichnikova, Dr. Sci. (Med.), CEO

25167, Moscow


O. A. Aleshina
National Medical Research Center for Hematology
Russian Federation

Olga A. Aleshina, Cand. Sci. (Med.)

25167, Moscow


V. V. Troitskaya
National Medical Research Center for Hematology
Russian Federation

Vera V. Troitskaya, Cand. Sci. (Med.), First Deputy Director

25167, Moscow


Yu. A. Chabaeva
National Medical Research Center for Hematology
Russian Federation

Yulia A. Chabaeva, Cand. Sci. (Tech.), Deputy Head of the Information and Analysis Department

25167, Moscow


A. N. Sokolov
National Medical Research Center for Hematology
Russian Federation

Andrey N. Sokolov, Cand. Sci. (Med.), Senior Researcher, Department of Intensive High-Dose Chemotherapy for Hemoblastosis and Hematopoietic Depressions with Hematopoietic Stem Cell and Bone Marrow Transplantation Unit

25167, Moscow


G. A. Isinova
National Medical Research Center for Hematology
Russian Federation

Galina A. Isinova, Cand. Sci. (Med.), Hematologist, Department of Intensive High-Dose Chemotherapy for Hemoblastosis and Hematopoietic Depressions
with Hematopoietic Stem Cell and Bone Marrow Transplantation Unit

25167, Moscow


E. S. Kotova
National Medical Research Center for Hematology
Russian Federation

Ekaterina S. Kotova, Hematologist, Department of Oncology and Chemotherapy for Hemoblastoses and Hematopoietic Depressions

25167, Moscow


Z. H. Akhmerzaeva
National Medical Research Center for Hematology
Russian Federation

Zalina Kh. Akhmerzaeva, Cand. Sci. (Med.), Hematologist, Department of Hematology and Chemotherapy of Acute Leukemia and Lymphomas

25167, Moscow


G. A. Klyasova
National Medical Research Center for Hematology
Russian Federation

Galina A. Klyasova, Dr. Sci. (Med.), Professor, Head of the Laboratory of Clinical Microbiology, Mycology and Antibiotic Therapy

25167, Moscow


I. V. Galtseva
National Medical Research Center for Hematology
Russian Federation

Irina V. Galtseva, Cand. Sci. (Med.), Head of the Laboratory of Blood and Bone Marrow Immunophenotyping

25167, Moscow


Yu. O. Davydova
National Medical Research Center for Hematology
Russian Federation

Yulia O. Davydova, Cand. Sci. (Med.), Clinical Diagnostition, Laboratory of Blood and Bone Marrow Immunophenotyping

25167, Moscow


L. A. Kuzmina
National Medical Research Center for Hematology
Russian Federation

Larisa A. Kuzmina, Cand. Sci. (Med.), Head of the Department of Intensive High-Dose Chemotherapy and Bone Marrow Transplantation

25167, Moscow


S. N. Bondarenko
Pavlov First Saint Petersburg State Medical University
Russian Federation

Sergey N. Bondarenko, Dr. Sci. (Med.), Associate Professor at the Department of Hematology, Transfusiology and Transplantology with a Course in Pediatric Oncology named after B.V. Afanasyev

197022, Saint Petersburg


O. Yu. Baranova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Olga Yu. Baranova, Cand. Sci. (Med.), Oncologist, Department of Hemoblastosis Chemotherapy

115478, Moscow


A. S. Antipova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Alina S. Antipova, Cand. Sci. (Med.), Hematologist, Oncologist, Department of Hemoblastosis Chemotherapy, Department of Hematology and Transplantation of Bone Marrow and Hematopoietic Stem Cells

115478, Moscow


O. S. Samoilova
N.A. Semashko Regional Clinical Hospital
Russian Federation

Olga S. Samoilova, Cand. Sci. (Med.), Head of the Hematology Department

603126, Nizhny Novgorod


M. E. Grishunina
N.A. Semashko Regional Clinical Hospital
Russian Federation

Maria E. Grishunina, Hematologist

603126, Nizhny Novgorod


K. D. Kaplanov
S.P. Botkin City Clinical Hospital
Russian Federation

Kamil D. Kaplanov, Cand. Sci. (Med.), Head of the Hematology Department № 11

125284, Moscow


T. S. Kaporskaya
Regional Clinical Hospital
Russian Federation

Tatyana S. Kaporskaya, Hematologist, Head of the Department of Hematology

664003, Irkutsk


T. S. Konstantinova
Regional Clinical Hospital № 1
Russian Federation

Tatyana S. Konstantinova, Cand. Sci. (Med.), Head of the Department of Hematology, Chemotherapy and Bone Marrow Transplantation

620102, Ekaterinburg


Yu. V. Sveshnikova
Regional Clinical Hospital № 1
Russian Federation

Julia V. Sveshnikova, Hematologist, Department of Hematology, Chemotherapy and Bone Marrow Transplantation

620102, Ekaterinburg

 


E. A. Borisenkova
Regional Clinical Hospital
Russian Federation

Elena A. Borisenkova, Head of the Department of Hematology

248007, Kaluga


E. S. Fokina
Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency
Russian Federation

Elena S. Fokina, Cand. Sci. (Med.), Hematologist, Deputy Head of the Department for Organization and Support of Scientific Research

610027, Kirov


N. V. Minaeva
Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency
Russian Federation

Natalia V. Minaeva, Cand. Sci. (Med.), Deputy Director for Medical Work

610027, Kirov


E. E. Zinina
Regional Clinical Hospital
Russian Federation

Elena E. Zinina, Head of the Clinical Diagnostic (Hematological) Center

628408, Surgut


V. A. Lapin
Regional Clinical Hospital
Russian Federation

Valeriy A. Lapin, Hematologist, Yaroslavl Regional Clinical Hospital, Chief Hematologist of the Department of Healthcare of Yaroslavl region

150062, Yaroslavl


E. O. Gribanova
National Medical Research Center for Hematology
Russian Federation

Elena O. Gribanova, Cand. Sci. (Med.), Head of the Department of Intensive High-Dose Chemotherapy for Hematological Diseases

125167, Moscow


E. E. Zvonkov
National Medical Research Center for Hematology
Russian Federation

Eugene E. Zvonkov, Dr. Sci. (Med.), Head of the Department of Hematology and Chemotherapy of Lymphomas with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit

125167, Moscow


V. N. Dvirnyk
National Medical Research Center for Hematology
Russian Federation

Valentina N. Dvirnyk, Cand. Sci. (Med.), Head of the Central Clinical Diagnostic Laboratory

125167, Moscow


G. M. Galstyan
National Medical Research Center for Hematology
Russian Federation

Gennady M. Galstyan, Dr. Sci. (Med.), Head of the Resuscitation and Intensive Care Department

125167, Moscow


T. N. Obukhova
National Medical Research Center for Hematology
Russian Federation

Tatiana N. Obukhova, Cand. Sci. (Med.), Head of the Karyology Laboratory

125167, Moscow


A. B. Sudarikov
National Medical Research Center for Hematology
Russian Federation

Andrey B. Sudarikov, Dr. Sci. (Biol.), Head of the Laboratory of Molecular Hematology

125167, Moscow


S. M. Kulikov
National Medical Research Center for Hematology
Russian Federation

Sergei M. Kulikov, Cand. Sci. (Tech.), Head of the Information and Analysis Department

125167, Moscow


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Review

For citations:

Parovichnikova E.N., Aleshina O.A., Troitskaya V.V., Chabaeva Yu.A., Sokolov A.N., Isinova G.A., Kotova E.S., Akhmerzaeva Z.H., Klyasova G.A., Galtseva I.V., Davydova Yu.O., Kuzmina L.A., Bondarenko S.N., Baranova O.Yu., Antipova A.S., Samoilova O.S., Grishunina M.E., Kaplanov K.D., Kaporskaya T.S., Konstantinova T.S., Sveshnikova Yu.V., Borisenkova E.A., Fokina E.S., Minaeva N.V., Zinina E.E., Lapin V.A., Gribanova E.O., Zvonkov E.E., Dvirnyk V.N., Galstyan G.M., Obukhova T.N., Sudarikov A.B., Kulikov S.M. Comparison of the treatment results in adult patients with acute Ph-negative lymphoblastic leukemia on protocols of the Russian multicenter studies ALL-2009 and ALL-2016. Russian journal of hematology and transfusiology. 2022;67(4):460-477. (In Russ.) https://doi.org/10.35754/0234-5730-2022-67-4-460-477

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ISSN 0234-5730 (Print)
ISSN 2411-3042 (Online)

125167, Moscow, New Zykovsky proezd. 4
National Medical Research Center for Hematology, Moscow, Russian Federation (Russia)
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