0
selected
-
1.
Trends in Outcome of Hematopoietic Stem Cell Transplantation: 5000 Transplantations and 30 Years of Single-Center Experience
Zubarovskaya, L. S., Moiseev, I. S., Vladovskaya, M. D., Mikhailova, N. B., Morozova, E. V., Bykova, T. A., Vlasova, Y. Y., Paina, O. V., Kazantsev, I. V., Slesarchuk, O. A., et al
Cancers. 2023;15(19)
Abstract
In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4-0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010-2014 vs. 38% in 2015-2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23-0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin's disease (HR 0.1, 95% CI 0.1-0.3), multiple myeloma (HR 0.4, 95% CI 0.2-0.7) and solid tumors (HR 0.2, 95% CI 0.2-0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1-0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1-0.5), Hodgkin's disease (HR 0.1, 95% CI 0.0-0.4), non-Hodgkin's lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0-0.6), inborn diseases (HR 0.2, 95% CI 0.2-0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2-0.8).
-
2.
A pilot study of implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia
Afanaseva, K. S., Bakin, E. A., Smirnova, A. G., Barkhatov, I. M., Gindina, T. L., Moiseev, I. S., Bondarenko, S. N.
Scientific reports. 2023;13(1):16790
Abstract
The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis. In this study, we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with a median age of 30 (range 18-55) years who previously underwent allo-HSCT, were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT. They were used to model relapse risk with several machine-learning approaches. GBM proved superior to the other algorithms and provided a maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment, and chronic GvHD had the highest value in the model. It was shown that after Day + 100, both error rates do not exceed 22%, while before D + 100, the model fails to make accurate predictions. As a result, we determined BCR::ABL1 levels at which the relapse risk remains low. Thus, the current BCR::ABL1 level less than 0.06% in patients with chronic GvHD predicts low risk of relapse. At the same time, patients without chronic GVHD after allo-HSCT should be classified as high risk with any level of BCR::ABL1. GBM model with posttransplant laboratory values of BCR::ABL1 provides a high prediction of relapse after allo-HSCT in the era of TKIs prophylaxis. Validation of this approach is warranted.
-
3.
Graft-versus-host disease prophylaxis with posttransplantation bendamustine (PTB) in patients with refractory acute leukemia: a dose-ranging study: Category of manuscript: Regular Manuscript
Moiseeev, I. S., Bondarenko, S. N., Morozova, E. V., Vlasova, Y. Y., Dotsenko, A. A., Epifanovskaya, O. S., Babenko, E. V., Botina, A. V., Baykov, V. V., Surkova, E. A., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10-15% of patients are cured by the procedure. Preclinical studies indicate that substitution of posttransplantation cyclophosphomide (PTCY) with bendamustine (PTB) in a prophylaxis regimen may be associated with augmented graft-versus-leukemia (GVL) reaction. OBJECTIVE establish the optimal dose of PTB and evaluate the anti-leukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. STUDY DESIGN In the prospective trial (NCT02799147) PTB was administered in doses 140, 100 and 70 mg/m2 on days +3,+4. Myeloablative conditioning with fludarabine and oral busulfan was performed in all patients. First 12 patients received single-agent PTB and subsequent- combination with tacrolimus and MMF. Inclusion criteria were acute myeloblstic (AML) or lymphoblstic leukemia (ALL) refractory to at least on induction course of chemotherapy or target therapy and =5% clonal blasts in the bone marrow. Seven patients were enrolled in the 140 mg/m2 cohort (due to stopping rule), 10 in 100 mg/m2 and 10 in 70 mg/m2 group, including 22 with AML and 5 with ALL. Primary refractory disease was documented in 41% of patients and secondary refractory - in 59%. Median blast count in the bone marrow at the start of the conditioning was 18% (range 6-97%). Matched sibling transplantation was performed in 5 patients, matched or mismatched unrelated in 15, and haploidentical in 7. RESULTS Engraftment was documented in 93% of patients, including 89% with complete remission (CR) and 63% without measurable residual disease (MRD). After PTB prophylaxis we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3-5 in 44% of patients. Most often clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation (DIC) in 37%, CNS toxicity in 26%. Development of CRS was associated with HLA-mismatched donor (75% vs 20%, p= 0.0043). Classical acute GVHD was documented in 44% of patients. Grade II-IV acute GVHD was associated with grade 3-5 CRS (67% vs 25%, p=0.031). Moderate and severe chronic GVHD in the 100-day survivors was more often observed after single-agent PTB than after the combination immunosuppression (100% vs 18%, p=0.002). Relatively low relapse incidence was observed for this patient population. Three-year overall survival was 28% (95% CI 13-46%), event-free-survival 29% (95% CI 13-46%). NRM was 46% (95% CI 25-64%), CIR was 26% (95%CI 11-44). No relapses were documented after day+100. There was no statistical differences between the dose groups (p=0.3481), however the survival was higher in the 100 mg/kg group. The survival was higher in AML than ALL (35% vs 0%, p=0.0157). CONCLUSION PTB represents a promising option to augment GVL effect in refractory AML, however high CRS-associated mortality requires additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.
-
4.
Graft-versus-Host Disease Prophylaxis in Unrelated Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil
Moiseev, I. S., Pirogova, O. V., Alyanski, A. L., Babenko, E. V., Gindina, T. L., Darskaya, E. I., Slesarchuk, O. A., Bondarenko, S. N., Afanasyev, B. V.
Biology of Blood & Marrow Transplantation. 2016;22(6):1037-42
Abstract
Clinical efficacy of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has been demonstrated in haploidentical and HLA-matched bone marrow but not in unrelated peripheral blood stem cell (PBSC) transplantations. Also, no direct comparisons have been published with current standard of care, combination of antithymocyte globulin (ATG), calcineurin inhibitors, and either methotrexate or mycophenolate mofetil (MMF). Eighty-six adult patients (median age 34 years; range, 18 to 59) with acute myeloblastic and lymphoblastic leukemia underwent unrelated PBSC transplantation with PTCy, tacrolimus, and MMF as GVHD prophylaxis in the single-center trial (clinicaltrial.govNCT02294552). The control group comprised 125 consecutive historical control patients who received ATG, tacrolimus, and methotrexate or MMF. Cumulative incidences of grades II to IV acute (19% versus 45%, P = .0003), grades III to IV acute (4% versus 27%, P < .0001), and chronic GVHD (16% versus 65%, P < .0001) were significantly lower in the PTCy compared with the ATG group. PTCy-based prophylaxis was associated with reduced incidence of nonrelapse mortality (16% versus 36%, P = .005; HR, .55; 95% CI, .34 to .89) and improved overall survival (69% versus 40%, P = .0007; HR, .43; 95% CI, .26 to .70), event-free survival (65% versus 38%, P = .0006; HR, .49; 95% CI, .31 to .78), and GVHD relapse-free survival (52% versus 12%, P < .0001). PTCy-based prophylaxis also had a better safety profile compared with ATG with reduced incidence of veno-occlusive disease, cytomegalovirus reactivation, invasive mycosis, and reduced severity of mucositis. In this study we demonstrated that PTCy in combination with tacrolimus and MMF is a safe and effective GVHD prophylaxis for unrelated PBSC transplantation. Although there are several limitations of the historical control approach, this study suggests the superiority of a PTCy-based approach over an ATG-based prophylaxis. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.