The safety and effctiveness of donor memory T lymphocyte infusions after hematopoietic stem cell transplantation with ab T cell depletion platform in children with acute leukemia

Abstract

T-cell ab depletion prevents “graft-versus-host” disease (GVHD), does not impair engraftment, and improves the outcomes of hematopoietic stem cell transplantation (HSCT) from a haploidentical donor. Memory T lymphocyte infusions (CD45RA-depleted) can transfer functional immunity to common pathogens to recipients. In a randomized study, we explored the safety and effctiveness of donor memory T lymphocyte infusions (DLI) in children with leukemia after HSCT with ab T cell depletion platform.  The study was approved by the Independent Ethics Committee and the Scientifi Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation. A total of 149 patients were enrolled in the study; 76 patients were randomly assigned to the DLI group and 73 patients were allocated to the control group. Donors were haploidentical related in 91% of cases. The myeloablative conditioning regimen included treosulfan and total body irradiation. Anti-thymocyte globulin (ATG) was excluded from the conditioning regimen, instead, we used a combination of abatacept and tocilizumab. Graft processing involved TCRab-/CD19-depletion. The main parameters of assessment included the cumulative risk of detection of cytomegalovirus (CMV) DNA and the cumulative risk of grade II–IV GVHD. The additional parameters of assessment were the cumulative risk of transplant-related mortality, the cumulative risk of relapse, the overall and event-free survival rates, and the parameters of immune recovery. A historical control group was used to compare the primary outcomes of HSCT with ATG and an alternative immunomodulatory regimen (abatacept and tocilizumab). The cumulative risk of grade II–IV GVHD was 14% in the experimental group and 12% in the control group (p = 0.8). The cumulative risk of CMV viremia was 45% and 55% in the experimental and control groups, respectively (p = 0.4). In the prospective cohort, the rates of transplant-related mortality, the cumulative risk of relapse, and the overall survival were 2%, 25%, and 80%, respectively, without statistical diffrence between the arms. In the experimental group, we noticed a tendency toward an increase in the proportion of patients who developed an immune response to CMV in the early post-HSCT period. The substitution of ATG with tocilizumab and abatacept was not accompanied by a higher incidence of GVHD or graft failure; it was associated with signifiantly lower transplant-related mortality rates (2% vs 13%, p = 0.002) and improved immune recovery in the early post-HSCT period. Prophylactic infusions of donor memory lymphocytes are safe and may be used for further improvement in. the results of HSCT with ab T cell depletion platform.