Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies

Abstract

An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multiinstitutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3 þ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3 þ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P ¼ 0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3 þ and leukemia-specific lineages.

Feasibility of Treating Post-Transplantation Minimal Residual Disease in Children with Acute Leukemia

“…(21, 31, 32) Additionally, this may not be an option in those with pre-existing GVHD. (13, 33–37) Disappointingly, in our study, similar to other reports, use of DLI, even pre-emptively, was not associated with long-term survival in patients with acute leukemia. (5, 21, 32, 38) Other treatment options for MRD, especially in the early post-transplant setting, are limited due to ongoing transplant-related co-morbidities.…”

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

“…After allo-HCT, length of stay and readmissions during the first 100 days after allo-HCT were also recorded. Other assessments after allo-HCT, such as engraftment, transfusion requirements, chimerism studies, presence of GVHD, organ toxicity, and disease status were collected using standard scoring scales [13,15–17]. …”

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

“…Donor whole blood and erythroid (CD71) donor chimerism was measured on days +30, 60, 100, 180, 365 and 730 (±10 days) using a semiquantitative method to measure the amplification products of genes containing STRs. 15,25 Immune reconstitution Absolute lymphocyte subset counts were measured pre-allo-SCT and at days +30, 60, 100, 180, 365 and 730 (±10 days).…”