Anti-T-lymphocyte globulin-based non-myeloablative stem cell transplantation followed by HLA-identical donor lymphocyte infusion for hematologic malignancies

Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.