title: Transplants across human leukocyte antigen barriers.
abstract: Clinical experience with full haplotype-mismatched stem cell transplants has a 20-year history. Early results in leukemia patients were disappointing because of a high incidence of severe graft-versus-host disease (GvHD) in T-replete transplants or high rejection rates in T-cell-depleted transplants. The breakthrough came with introduction of a megadose T-cell-depleted progenitor cell transplant following a high-intensity conditioning regimen and the realization that donor natural killer (NK) cell alloreactivity also plays a role in facilitating engraftment and in preventing relapse. Treating end-stage patients inevitably confounded clinical outcome in early pilot studies. Today, high-risk acute leukemia patients are treated at less advanced stages of disease, receive a reasonably well-tolerated conditioning regimen, and benefit from advances in post-transplant immunological reconstitution. These factors have markedly reduced transplant-related mortality. Overall, event-free survival (EFS) and transplant-related mortality (TRM) compare favorably with reports from unrelated matched transplants. T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can now be offered as a viable option to candidates with high-risk acute leukemias.
authors.affiliation: Department of Hematology, University of Perugia, Perugia, Italy.
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Ester
authors.initials: E
authors.lastname: Bachar-Lustig
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reich-Zelicher
authors.forename: Antonio
authors.initials: A
authors.lastname: Tabilio
authors.forename: Hilit
authors.initials: H
authors.lastname: Gur
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D008212:Lymphocyte Depletion; D019172:Transplantation Conditioning / Q000379:methods; D014181:Transplantation Immunology; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens