Haploidentical cord transplantation-The best of both worlds

Haploidentical (haplo)-cord transplantation combines infusion of an umbilical cord blood (UCB) unit with CD34-selected cells usually from human leukocyte antigen (HLA) mismatched donors. Initial rapid count recovery from the haplo-hematopoietic progenitors, is gradually replaced by durable engraftment from UCB progenitors. UCB grafts used for haplo-cord are smaller, but better matched than those required for single or double UCB stem cell transplant (SCT). More than 200 patients with hematological malignancies have been transplanted. Median age was 54 years (range 17-74) and 77 were over age 60. One-year survival was 64% for patients with intermediate- and low-risk disease, with no deaths beyond 2 years. In high-risk disease, 1-year survival was 44%. In a comparison with patients undergoing double UCB SCT, haplo-cord transplant resulted in faster hematopoietic recovery, lower rates of acute and chronic graft-versus-host disease (GVHD), lower rates of disease recurrence, and improved GVHD- and relapse-free survival (GRFS). Excellent results were also reported for patients with aplastic anemia where 18 of 21 patients had sustained cord blood engraftment. Rates of GVHD and of disease recurrence after haplo-cord are encouraging. However, in the approximately 10% of patients with failure of the UCB graft disease recurrence is high, supporting the important role of UCB-mediated graft-versus-leukemia (GVL). Ongoing efforts are aimed at identifying determinants of UCB engraftment, at reducing rates of disease recurrence in high risk patients and at optimizing dose and schedule of ATG -necessary to avoid early haplo-graft rejection, but also contributing to early post-transplant immunocompromise. For those lacking haploidentical donors, unrelated donors have been successfully utilized.