A comparison of ex vivo and in vivo T-cell depletion for hematopoietic stem cell transplantation in children with malignant blood disorders

A decrease in T cell alloreactivity following hematopoietic stem cell transplantation (HSCT) can be achieved via the depletion of TCR_ab⁺ and CD19⁺ lymphocytes or post-transplant therapy with high-dose cyclophosphamide (PTCy). The purpose of this study was to analyze HSCT outcomes according to the type of lymphocyte depletion. In our non-randomized retrospective study, we analyzed the results of 118 HSCTs performed in 107 patients with malignant blood disorders at the Center for Pediatric Oncology and Hematology of the Regional Children’s Clinical Hospital (Yekaterinburg) from 2010 to 2023. The patients were divided into 2 groups: those who had received ex vivo TCR_ab⁺/CD19⁺ depletion using the CliniMACS technology (n = 75; Group 1) and those who had received in vivo depletion using PTCy at a dose of 50 mg/kg (n = 43; Group 2). The study was approved by the Independent Ethics Committee and the Scientific Council of the Institute of Medical Cell Technologies (Yekaterinburg). Informed consent for the research and treatment was obtained from each patient and their legal representatives. Even though the patients from the TCR_ab⁺/CD19⁺ depletion group showed a better engraftment rate (median time: 12 days) than the subjects from the PTCy group (median time: 18 days) (p < 0.0001), there was no statistically significant difference in the cumulative incidence of cytomegalovirus and herpesvirus type 6 infection reactivation post-transplant between the two study groups. The cytomegalovirus reactivation rate was 0.467 and 0.466 in Group 1 and 2 respectively (p = 0.89), while for herpesvirus type 6 the reactivation rate was 0.360 and 0.240 respectively (p = 0.13). There were no significant differences in the cumulative incidence of acute graft-versus-host disease (GVHD) in the two groups by Day +100 (0.294 and 0.419 in Group 1 and 2 respectively; p = 0.77); neither was there any difference in the incidence of severe acute GVHD (0.067 and 0.093 respectively; p = 0.11). The incidence of chronic GVHD was 0.12 in the TCR_ab⁺/CD19⁺ depletion group and 0.26 in the PTCy group (p = 0.11). The event-free survival, overall survival and cumulative incidence of relapse did not differ between the studied groups either. The two methods of the depletion of unwanted T-cell populations showed a comparable effectiveness. The choice between them should be based on factors related to the biological characteristics of the disease and the clinical status of a patient. The availability of different depletion methods at a single transplant center helps to choose the optimal treatment option for patients who are in need of HSCT.