Unrelated donor α/β T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia.
Unrelated donor α/β T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia.
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DOI：
10.1182/bloodadvances.2021005492
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发表时间：
2022-02-22
期刊：
影响因子：
7.5
通讯作者：
Bunin N
中科院分区：
文献类型：
--
作者：
Leahy AB;Li Y;Talano JA;Elgarten CW;Seif AE;Wang Y;Johnson B;Monos DS;Kadauke S;Olson TS;Freedman J;Wray L;Grupp SA;Bunin N
URD HSCT with TCRαβ/CD19 depletion is a safe and effective approach to alternative donor transplantation for hematologic malignancies. Nonpermissive mismatch at DP was associated with a 16.5-fold risk of acute GVHD and may represent a modifiable target to mitigate GVHD risk. Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe graft-versus-host disease (GVHD). TCRαβ/CD19 depletion may reduce this risk, whereas maintaining graft-versus-leukemia. Outcome data with TCRαβ/CD19 depletion generally describe haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at 2 large pediatric transplantation centers between October 2014 and September 2019. All patients with acute leukemia had minimal residual disease testing, and DP typing was available for 77%. All patients received myeloablative total body irradiation– or busulfan-based conditioning with no posttransplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95% confidence interval [CI], 52%-81%), and leukemia-free survival was 64% (95% CI, 48%-76%), with no difference between lymphoid and myeloid malignancies (P = .6297 and P = .5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence, 21%; 95% CI, 11-34), and 8 patients (cumulative incidence, 15%; 95% CI, 6.7-26) experienced nonrelapse mortality. Grade III to IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Nonpermissive DP mismatch was associated with higher likelihood of acute GVHD (odds ratio, 16.50; 95% CI, 1.67-163.42; P = .0166) but not with the development of chronic GVHD. URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.
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