CD6-Depleted Mobilized Stem Cells for Modification of HVG and GVH Reactions after HLA-Haploidentical Marrow Transplantation.

Allogeneic stem cell transplantation is limited to patients with a histocompatible donor, but for patients with advanced acute leukemia and high-grade lymphoma HLA-haploidentical transplantation may be considered. Rejection of the transplant and graft-versus-host disease are major obstacles and T-cell depletion eliminates the graft-versus-leukemia effect and causes prolonged immune deficiency. Here we studied the use of CD6-depleted G-CSF mobilized blood cells (mbc) 6 days after transplantation of unmodified marrow in order to suppress host-versus-graft and graft-versus-host reactions (GVHD) retaining a graft-versus-leukemia effect and the capacity to reconstitute the immune system. CD6-depleted mbc contain a large proportion of NK and NK-T cells. 63 patients with advanced disease (AML 32, ALL 15, NHL 11, CLL 2, CML 2, SAA 1) were transplanted with marrow from family donors sharing one HLA-haplotype and differing in 0 – 4 HLA-antigens of the second haplotype. Conditioning consisted of total body irradiation (TBI), antithymocyte globulin (ATG) and cyclophosphamide (CY), post-grafting immunosuppression of cyclosporin A (CSA) and a short course of methotrexate (sMTX). A transfusion of donor leukocytes was given prior to CY. Complete engraftment was observed in 34 evaluable patients given 12 Gy TBI. The dose of TBI could be reduced to 4 Gy without rejection in 25 evaluable patients. GVHD was severe (grade III and IV) in 12 of 48 evaluable patients. An improved method of CD6-depletion was administered to mbc in 9 patients and severe GVHD did not develop. GVHD responded to corticosteroids in most patients. 15 patients survive disease free up to 6 years (median 784 days). Recurrent infections including PTLD were the major cause of transplant-related mortality. Absolute counts of lymphocytes, CD4 and CD8 subpopulations were not different from those of a contemporary group of 46 patients in advanced disease given HLA-identical sibling transplants. However naïve CD4 cells and TRECs were low. Rejection, GVHD and GVL have been controlled by this regimen, but immune reconstitution remains a problem that may be solved by early discontinuation of immunosuppression in this regimen.