Full Haplotype-Mismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse

Abstract

Our transplantation procedure provides reliable, reproducible CD34+ cell purification, high engraftment rates, and prevention of GvHD. The mismatched-related transplant emerges as a viable, alternative source of stem cells for acute leukemia patients without matched donors and/or those who urgently need transplantation.

The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach

“…While the probability of identifying an adult unrelated donor may be as high as 60% for Caucasian patients, still a considerable number of patients with a diverse ethnic background lack a suitable donor. Alternative donors and/or stem cell sources include unrelated cord blood and haploidentical family donors (77)(78)(79)(80)(81)(82). Currently, in many centers, such transplants are not routinely performed in patients with AML in first CR given the higher NRM associated with these donors/stem cell sources.…”

The great debate: haploidentical or cord blood transplant

“…No consensus has been reached on the optimal strategy for performing haploidentical HCT, and going forward, innovative strategies to modulate the cellular environment post transplant likely will lead to improvements in outcome compared with previously published data. Event-or leukemia-free survival probabilities for patients with AML and ALL in remission of 48 to 70.7% and 46 to 59%, respectively, in two of the larger haploidentical HCT trials, 29,32 as discussed above, are encouraging. Furthermore, in a retrospective, multicenter analysis from the European Blood and Marrow Transplant Group, 42 leukemia-free survival probabilities of 48 and 21% for patients with AML in first CR, or second or later remission, appear to be comparable to the best results of UCB transplantation.…”

“…Haploidentical HCT outcomes, however, have improved considerably over the past decade as a result of many advancements in GVHD prevention. [27][28][29][30][31][32] These successful strategies had included ex vivo T-cell depletion of the hematopoietic cell graft and/or in vivo T-cell depletion using antithymocyte globulin, alemtuzamab, vigorous pharmacologic anti-GVHD therapy, or combinations have improved patient outcome. Finally, technological advances in supportive care, including potent antiviral and antifungal agents, and the ability to modulate the cellular environment post transplant via adoptive cellular immunotherapy, such as donor lymphocyte infusion, have resulted in making haploidentical HCT an attractive option for patients who are in need of an alternative donor transplant.…”

“…29 For patients not in remission at the time of their transplant, distinctly inferior disease-free and OS probabilities were realized. A non-relapse mortality risk of 38%, principally because of opportunistic infection, demonstrated the highrisk nature of this strategy and the need for interventions to improve immune reconstitution post transplant.…”

“…Modern haploidentical HCT approaches most commonly have involved three general strategies: (1) myeloablative conditioning with vigorous ex vivo T cell-depleted (usually via CD34 þ cell selection) or anergized high-dose PBPC transplantation; 28,29,32 (2) RIC with ex vivo and/or in vivo T-cell depletion, and post transplant pharmacoprophylaxis or post transplant CY; 27,39,31 (3) myeloablative conditioning with in vivo T-cell depletion, non ex vivo T cell-depleted HCT and post transplant GVHD pharmacoprophylaxis. 32 Haploidentical HCT outcomes Most published haploidentical HCT series have been small (with o100 patients) and have included patients with diverse diseases and remission states at the time of transplantation.…”