Transplantation of haploidentically mismatched stem cells for the treatment of malignant diseases.
Hematopoietic stem cell transplantation (HSCT) from HLA haploidentical mismatched donors has recently been developed for patients with high-risk acute leukemia who do not have a matched donor. After a high intensity conditioning regimen the HLA barrier is overcome by infusing a graft containing a megadose of T cell-depleted progenitor cells. Nowadays, for graft processing automated peripheral blood CD34(+) cell immunoselection is time and labor saving and ensures a high CD34(+) cell recovery rate. Besides providing 4.5 log T cell depletion of the graft, it guarantees a 3.5 log B cell depletion, which helps prevent EBV-related lymphoproliferative disorders. Excellent engraftment rates are associated with a very low incidence of graft-versus-host disease and regimen-related mortality even in patients who are over 40 years old. Overall, event-free survival and transplant-related mortality compare favorably with reports from unrelated matched transplants. Donor natural killer cell alloreactivity also plays a role in improving outcome in patients with acute myeloid leukemia. These results show the haploidentical transplant to be a viable, alternative source of stem cells for adults with acute leukemia at high-risk of relapse who do not have matched donors, and encourage extending it to patients with an indication to transplant.
Aversa
Franco
F
Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Via Brunamonti, 06123 Perugia, Italy. aversa@unipg.it
Martelli
Massimo F
MF
D000208:Acute Disease; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D006680:HLA Antigens