title: Haploidentical transplantation for hematologic malignancies: where do we stand?
abstract: The fundamental obstacle to the successful application of partially HLA-mismatched related donor, or HLA-haploidentical stem cell transplantation, is the strength of the host and donor T-cell response to allogeneic HLA molecules, which results in increased incidences of graft failure, GVHD, and nonrelapse mortality. The holy grail of haplo-SCT is to mitigate host-versus-graft and graft-versus-host responses while preserving immune responses to infection and the patient's malignancy. Two strategies have been taken to achieve this goal. The first strategy is to supplement a T cell-depleted graft with pathogen-specific T cells or populations of T cells in which alloreactivity can be controlled. The second strategy is to eliminate alloreactive T cells selectively from a T cell-replete graft. Substantial progress has been made with both approaches so that the safety of haplo-SCT now approaches that of SCT using grafts of umbilical cord blood or from HLA-matched donors. In light of the rapid and near universal availability of HLA-haploidentical related donors, it should now be possible to identify and mobilize a donor for every patient referred for allogeneic SCT. Prospective comparisons between haploidentical SCT and unrelated donor SCT should be performed to identify the most efficacious approach to alternative donor transplantation.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA. fuchsep@jhmi.edu
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
mesh_terms: D000483:Alleles; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006680:HLA Antigens / Q000737:chemistry; D019337:Hematologic Neoplasms / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007107:Immune System; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D003520:Cyclophosphamide