Chimerism-based pre-emptive immunotherapy with fast withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic stem cell transplantation for pediatric hematologic malignancies.

The presence of increasing host chimerism or persistent mixed chimerism (MC) after hematopoietic stem cell transplantation for leukemia in children is a predictor of relapse. To reduce the risk of relapse, we prospectively studied post-transplantation chimerism-based immunotherapy (IT) using fast withdrawal of immunosuppression (FWI) and donor lymphocyte infusions (DLI) in children with early post-transplantation MC. Forty-three children with hematologic malignancies at 2 institutions were enrolled prospectively in this study from 2009 until 2012 and were followed for a mean of 42 (SD, 10) months. Twelve patients (28%) were assigned to the observation arm based on the presence of graft-versus-host disease (GVHD) or full donor chimerism (FDC), and 5 (12%) sustained early events and could not undergo intervention. Twenty-six (60%) patients with MC were assigned to IT with FWI, which started at a median of 49 days (range, 35 to 85 days) after transplantation. Fourteen patients proceeded to DLI after FWI. Toxicities of treatment included GVHD, which developed in 19% of patients undergoing intervention, with 1 of 26 (4%) dying from GVHD and 1 (4%) still requiring therapy for chronic GVHD 21 months after DLI. Patients with MC undergoing IT had similar 2-year event-free survival (EFS) (73%; 95% confidence interval (CI), 55% to 91%) compared with patients who achieved FDC spontaneously (83%; 95% CI, 62% to 100%); however, because 50% of all relapses in the IT occurred later than 2 years after transplantation, the EFS declined to 55% (95% CI, 34% to 76%) at 42 (SD, 11) months. There were no late relapses in the observation group. EFS in the entire cohort was 58% (95% CI, 42% to 73%) at 42 (SD, 11) months after transplantation. Evidence of disease before transplantation remained a significant predictor of relapse, whereas development of chronic GVHD was protective against relapse

Early mixed chimerism‐based preemptive immunotherapy in children undergoing allogeneic hematopoietic stem cell transplantation for acute leukemia

This retrospective analysis comprises 10-year experience with early posttransplant mixed chimerism-based preemptive intervention. Out of 104 patients, 51 received preemptive immunotherapy. Their outcomes were similar to patients achieving full donor chimerism spontaneously. Among patients receiving intervention, 5-year event-free survival was identical in patients with and without pretransplant residual disease, respectively (68% [95% confidence interval (CI) 38-98%] vs. 69% [95% CI 54-85%] log-rank = 0.4). In patients who received preemptive immunotherapy, chimerism status and residual disease prior to transplant were no longer predictors of poor outcome; however, 41% of the patients with residual disease prior to transplant relapsed early and did not benefit from this strategy

Chimerism-Based Pre-Emptive Immunotherapy with Fast Withdrawal of Immunosuppression and Donor Lymphocyte Infusions after Allogeneic Stem Cell Transplantation for Pediatric Hematologic Malignancies

AbstractThe presence of increasing host chimerism or persistent mixed chimerism (MC) after hematopoietic stem cell transplantation for leukemia in children is a predictor of relapse. To reduce the risk of relapse, we prospectively studied post-transplantation chimerism-based immunotherapy (IT) using fast withdrawal of immunosuppression (FWI) and donor lymphocyte infusions (DLI) in children with early post-transplantation MC. Forty-three children with hematologic malignancies at 2 institutions were enrolled prospectively in this study from 2009 until 2012 and were followed for a mean of 42 (SD, 10) months. Twelve patients (28%) were assigned to the observation arm based on the presence of graft-versus-host disease (GVHD) or full donor chimerism (FDC), and 5 (12%) sustained early events and could not undergo intervention. Twenty-six (60%) patients with MC were assigned to IT with FWI, which started at a median of 49 days (range, 35 to 85 days) after transplantation. Fourteen patients proceeded to DLI after FWI. Toxicities of treatment included GVHD, which developed in 19% of patients undergoing intervention, with 1 of 26 (4%) dying from GVHD and 1 (4%) still requiring therapy for chronic GVHD 21 months after DLI. Patients with MC undergoing IT had similar 2-year event-free survival (EFS) (73%; 95% confidence interval (CI), 55% to 91%) compared with patients who achieved FDC spontaneously (83%; 95% CI, 62% to 100%); however, because 50% of all relapses in the IT occurred later than 2 years after transplantation, the EFS declined to 55% (95% CI, 34% to 76%) at 42 (SD, 11) months. There were no late relapses in the observation group. EFS in the entire cohort was 58% (95% CI, 42% to 73%) at 42 (SD, 11) months after transplantation. Evidence of disease before transplantation remained a significant predictor of relapse, whereas development of chronic GVHD was protective against relapse