Outcome of children with acute leukemia given HLA-haploidentical HSCT after ab T-cell and B-cell depletion

Outcome of children with acute leukemia given HLA-haploidentical HSCT after ab T-cell and B-cell depletion
Haploidentical hematopoietic stem cell transplantation (HSCT) is an option for transplantation in patients without a suitable matched donor. CD34+ positive selection is traditionally used to prevent both graft failure and severe graft-versus-host disease (GVHD), but is associated with prolonged lymphopenia and delayed immune reconstitution. Selective depletion of (alpha-beta) T lymphocytes and B cells from a haploidentical donor allows transplantation of both donor hematopoietic stem cells and also committed progenitor cells, NK cells, and (gamma-delta) T lymphocytes to improve post-transplant immune reconstitution and decrease life-threatening infections.
In this prospective trial, children with acute lymphoblastic or myelogenous leukemia without an available matched sibling or unrelated donor were offered a selectively cytoreduced haploidentical transplant. All patients received myeloablative conditioning, anti-T lymphocyte globulin for GVHD prophylaxis and conditioning, and Rituximab for EBV-related PTLD prophylaxis. This cohort was compared to children receiving either a matched sibling or matched unrelated transplant in the same period at the centre.
80 children were enrolled in the cohort; two failed to engraft. No serious acute GVHD occurred, and the overall incidence of limited chronic GVHD was only 5%. Four patients died of treatment-related causes, for a 5-year cumulative incidence of 5%. 19 patients (24%) have relapsed, with 15 in the first year after transplantation; only use of total body irradiation had a significant impact on relapse rate in multivariate analysis. 5-year overall survival was 72%, and this group was comparable to the compared matched sibling and unrelated groups.
Novel approaches such as post-transplantation cyclophosphamide were not evaluated in this regimen, which might allow for decreased intensity of conditioning. Rituximab prophylaxis may have contributed to the low incidence and severity of acute GVHD through recipient B-cell depletion. This was a single-centre trial of a highly specialised graft-manipulation, less experienced centers might not be able to achieve the same quality of graft manipulation.
Even in the absence of post-transplantation pharmacological prophylaxis, patients receiving a selectively (alpha-beta) T-cell and B-cell depleted haploidentical HSC had both a high engraftment rate and a low incidence of GVHD. This type of transplantation offers comparable risks of treatment-related morbidity and mortality and relapse for patients who would otherwise lack a suitable donor.

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