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
Authors: 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. 
Published: December 2022

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.