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.
High prevalence of CD3, NK, and NKT cells in the graft predicts adverse outcome after matched-related and unrelated transplantations with post transplantation cyclophosphamide
Moiseev, I. S., Babenko, E. V., Epifanovskaya, O. S., Sergeev, V. S., Dotcenko, A. A., Bakin, E. A., Surkova, E. A., Kuznetsova, D. A., Lapin, S. V., Pirogova, O. V., et al
Bone marrow transplantation. 2019
Abstract
The predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93, p = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vbeta11, and double-positive cells in the PBSC grafts from young donors (HR 2.75, p = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.