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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.

Introduction. Life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) can have a significant influence on the short-term and long-term prognosis in recipients of hematopoietic stem cells (allo-HSCs).Aim — to determine the life-threatening complications and the risk factors of their occurrence and to evaluate the short-term and long-term prognosis in critically ill allo-HSCs recipients.Materials and methods. All patients over the age of 18 who underwent allo-HSCT from 01.01.2012 to 01.01.2022 were included in the retrospective study. Patients were divided into two groups: those who required intensive care unit (ICU) admission and those who did not require ICU admission. In the group of ICU admitted allo-HSCs recipients the reasons of ICU admission, timing of their occurrence and the results of life support were recorded. The risk factors of life-threatening complications occurrence and prognostic factors were analyzed.Results. In total, 174 (26.7 %) of 652 allo-HSCs recipients required ICU admission. The risk factors of life-threatening complications were: allo-HSCT in patients with acute leukemia who did not achieve complete remission (hazard ratio (HR) = 2.10; 95 % confidence interval (95% CI): 1.28–3.44; p = 0.003), allo-HSCT without conditioning in patients with hematopoietic aplasia after chemotherapy (HR = 30.63; 95% CI: 8.787–107.04; p < 0.001), graft failure (HR = 2.51; 95% CI: 1.58–3.97; p < 0.001) and poor graft function (HR = 2.85; 95% CI: 1.6–5.05; p < 0.001), acute graft versus host disease (GVHD) (HR = 2.04; 95% CI: 1.459–2.85; p < 0.001). The main reasons of ICU admission were sepsis and/or septic shock (SS) (27.9 %), acute respiratory failure (23.9 %), neurological disorders (17.7 %). The type and periods of allo-HSCT influenced the timing and structure of critical illnesses. The ICU mortality rate after all ICU admissions and readmissions was 59.8 % with a maximum follow-up of 9 years. The risk factors of ICU mortality were the occurrence of critical conditions after +30 days of allo-HSCT, the need for mechanical ventilation and vasopressors. The overall survival (OS) rate of ICU admitted allo-HSCs recipients was 13.8 %. Sepsis and/or SS that occurred in the early phase after allo-HSCT were characterized by the most favorable long-term outcome (OS — 43.8 %) among all complications of the peritransplantation period. The OS of patients discharged from the ICU was worse than OS of patients who did not require ICU admission (34.6 % vs. 58.3 %; p = 0.0013). Conclusion. Transplant centers should have a specialized ICU because more than a quarter of allo-HSCT recipients experience life-threatening complications at different allo-HSCT periods. Sepsis and SS occurring in the early pre-engraftment phase had a more favorable prognosis than other life-threatening complications. The long-term outcomes in allo-HSCs recipients who survived critical illness are worse than in recipients who did not require ICU admission.

Introduction. Chronic graft versus host disease (GVHD) is a frequently occurring complication after transplantation of allogeneic hematopoietic cells associated with a decrease in the quality of life and long-term administration of immunosuppressive drugs. Extracorporeal photopheresis (ECP) is a second line of therapy after treatment failure with glucocorticoids.Aim — to evaluate the effects of ECP treatment in patients with glucocorticosteroids (GCS)-refractory, GCS-dependent or GCS -intolerant chronic GVHD.Materials and methods. 24 patients with GCS-refractory, GCS-dependent or GCS-intolerant chronic GVHD were included in the therapy with ECP. Nine patients had moderate chronic GVHD, and 15 had a severe chronic GVHD. Skin and mucous membranes were the most frequently targeted organs, 21 and 20 of 24 patients respectively, liver damage was detected in 8 patients. The maximum duration of treatment was 33 months (median — 8.5 months). The number of procedures of ECP ranged from 6 to 48 (median — 22).Results. A response was determined in 23 patients with one patient being excluded from the assessment due to a relapse of acute leukemia. 16 (69.5 %) patients achieved an overall response to ECP treatment. Three patients had complete response and full reduction of immunosuppressive therapy. When assessing organ-specific response, the most notable improvement was observed in the mucous membranes of 17 patients (89.4 %), skin — 17 (85 %), and liver — 7 (75 %). Along with achieving a general overall response, 78.2 % of patients partly reduced or completely canceled immunosuppressive therapy.Conclusion. ECP is an effective and promising second line treatment method for chronic GVHD in patients with GCS-refractory, GCS-dependent or GCS-intolerant forms.

Introduction. Autologous haematopoietic stem cell transplantation (auto-HSCT) is a highly effective treatment for multiple myeloma (MM). Auto-HSCT allows a signifi cant improvement of haematological response leading to higher overall survival and quality of life in MM patients. Nonetheless, the majority of patients develop relapse.Aim — a comparison of clinical MM relapses developing at variant terms after auto-HSCT.Patients and methods. A retrospective study enrolled 65 MM patients aged between 39 and 64 years. All patients had auto-HSCT during 2009–2019, all had achieved complete response (CR) or very good partial response (VGPR) and all since developed immunochemical MM relapse in laboratory evidence. Patients were divided in two cohorts by relapse term, the early (within 12 months of auto-HSCT) and late relapse.Results. Early immunochemical relapse was diagnosed in 13 (20 %), late relapse — in 52 (80 %) patients. The dependence between relapse term and depth of post-auto-HSCT antitumour response has been determined. The proportion of CR patients was signifi cantly higher in late than in early relapse (55.8 vs. 23 %). In follow-up, 60 patients (92.3 %) were initiated on antirelapse therapy, all early relapse and 90.3 % late relapse patients. On day +100 of auto-HSCT, CR patients had later relapse vs. VGPR individuals (median 24 vs. 19.9 months, p = 0.08) with signifi cantly weaker paraprotein secretion resembling the clinical course of monoclonal gammopathy of unclear signifi cance (MGUS).Conclusion. Auto-HSCT allows long-term control of the disease. A signifi cant prognostic factor is antitumour response on +100 day of auto-HSCT. Patients attaining CR have later relapse progressing in a MGUS-like manner. Patients with late indolent relapse can be managed long-term without antitumour therapy.