T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor.
Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using T-cell replete grafts and conventional immunosuppression were associated with unacceptable rates of GVHD, and when stringent ex vivo T-cell depletion was used to control GVHD, rates of graft rejection and post-transplant infections were prohibitive. The recent approach to HLA-haploidentical donor transplantation developed in Baltimore that uses T-cell replete grafts and post-transplant CY (Haplo-post-HCT-CY) to control post-transplant allo-reactivity appears to have overcome many of the obstacles historically associated with haploidentical donor transplantation. In particular, TRM rates of <10% are usual and rapid reconstitution of immunity leads to a low rate of post-transplant infections and no post-tranplant lymphoproliferative disorders (PTLD), consistent with the hypothesis that post-transplant CY selectively depletes proliferating alloreactive T cells responsible for GVHD and graft rejection while preserving resting memory T cells essential for post-transplant immunologic recovery. In parallel trials using similar non-myeloablative conditioning regimens, Haplo-post-HCT-CY produced similar overall survival to double umbilical cord blood transplantation(DUCBT) in adult patients (62% vs 54%), with low rates of TRM (7% vs 24%), severe acute GVHD (0% vs 21%) and chronic GVHD (13% vs 25%). Furthermore, recent non-randomized comparisons adjusted for risk factors show that Haplo-post-HCT-CY achieve at least equivalent outcomes to conventional MRD and MUD transplants. Although most experience has been obtained using BM, emerging data suggest that a G-CSF mobilized PBSC graft can also safely be used for Haplo-post-HCT-CY. Haplo-post-HCT-CY also avoids the graft acquisition costs of DUCBT and MUDs and the cost of cell selection associated with T-depleted grafts. Although randomized comparisons will be forthcoming, Haplo-post-HCT-CY can already be considered a valid standard-of-care in patients who lack conventional donors thus extending the availability of allogeneic transplants to almost all patients. This donor source may also challenge the routine preference for a MUD in patients lacking an MRD.
Blood and Marrow Transplant Program at Northside Hospital 5670 Peachtree Dunwoody Road NE Suite 1000, Atlanta, GA, USA.
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Bashey
Blood and Marrow Transplant Program at Northside Hospital 5670 Peachtree Dunwoody Road NE Suite 1000, Atlanta, GA, USA.
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Solomon
D000328:Adult; D002986:Clinical Trials as Topic; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D019520:Living Donors; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000628:therapy; D008297:Male; D035781:Siblings; D013601:T-Lymphocytes; D061349:Unrelated Donors