Allogeneic Peripheral Blood Stem Cell Transplantation from Related Donors Mismatched at 2 HLA Loci in the Host-versus-Graft Direction

In allogeneic stem cell transplantation, immune reactions can occur in 2 directions. The recipient's lymphocytes can recognize the donor's cells as “foreign” and attempt to kill them, which results in the host-versus-graft (HVG) reaction that is commonly termed graft rejection. The other direction is the graft-versus-host (GVH) reaction. When the recipient is homozygous at a mismatched human leukocyte antigen (HLA) locus, HLA disparity is present only in the former direction and not in the latter direction. If transplants harvested from such an HVG-mismatched donor can be used to achieve stable engraftment with minimal toxicity, then these donors can potentially be a useful alternative donor source. Here, we report 2 patients (1 with acute myeloblastic leukemia and another with lymphoblastic lymphoma) who were transplanted with peripheral blood stem cells (PBSCs) obtained from related donors mismatched at 2 HLA loci in the HVG direction but completely matched in the GVH direction. Our conditioning regimen, consisting of busulfan, cyclophosphamide, low-dose total body irradiation (TBI) (4 Gy), and fludarabine, achieved successful engraftment with an acceptable level of regimen-related toxicity. Our experience suggests that PBSC transplantation with an HVG-mismatched related donor and an appropriate conditioning regimen may be a therapeutic option for patients in whom early transplantation is desirable.