Outcomes of acute leukemia XXXX transplanted with naive T cell-depleted stem cell grafts.

@entity1 @entity19 @entity11678 @entity3118 @entity1778 @entity2132 @entity281 @entity1140 @entity2280 @entity7443
BACKGROUND: @entity2132 ( @entity2132 ) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT). In @entity19 , naive T cells ( @entity7443 ) cause more severe @entity2132 than memory T cells (TM). We hypothesized that selective depletion of @entity7443 from @entity1 allogeneic peripheral blood stem cell (PBSC) grafts would reduce @entity2132 and provide sufficient numbers of hematopoietic stem cells and TM to permit hematopoietic engraftment and the transfer of pathogen-specific T cells from donor to recipient, respectively. METHODS: In a single-arm clinical trial, we transplanted 35 @entity1 with @entity1778 with @entity7443 -depleted PBSC grafts following conditioning with total body irradiation, @entity11678 , and @entity3118 . @entity2132 prophylactic management was with @entity1140 immunosuppression alone. Subjects received @entity2280 -selected PBSCs and a defined dose of TM purged of CD45RA+ @entity7443 . Primary and secondary objectives included engraftment, acute and @entity2132 , and immune reconstitution. RESULTS: All recipients of @entity7443 -depleted PBSCs engrafted. The incidence of acute @entity2132 was not reduced; however, @entity2132 in these @entity1 was universally corticosteroid responsive. @entity2132 was remarkably infrequent (9%; median follow-up 932 days) compared with historical rates of approximately 50% with T cell-replete grafts. TM in the graft resulted in rapid T cell recovery and transfer of protective virus-specific immunity. Excessive rates of @entity281 or relapse did not occur and overall survival was 78% at 2 years. CONCLUSION: Depletion of @entity7443 from stem cell allografts reduces the incidence of @entity2132 , while preserving the transfer of functional T cell memory. TRIAL REGISTRATION: ClinicalTrials.gov (NCT 00914940).
