Transplants across human leukocyte antigen barriers.
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.
Martelli
Massimo F
MF
Department of Hematology, University of Perugia, Perugia, Italy.
Aversa
Franco
F
Bachar-Lustig
Ester
E
Velardi
Andrea
A
Reich-Zelicher
Shlomit
S
Tabilio
Antonio
A
Gur
Hilit
H
Reisner
Yair
Y
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
D006680:HLA Antigens