Unrelated donor α/β T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia.

Autor:	Leahy AB; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Penn Center for Cancer Care Innovation, Abramson Cancer Center at the Perelman Center for Advanced Medicine, and.; Department of Pediatrics, and., Li Y; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Talano JA; Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI; and., Elgarten CW; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Seif AE; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Wang Y; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Johnson B; Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI; and., Monos DS; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Kadauke S; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Olson TS; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Freedman J; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Wray L; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Grupp SA; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and., Bunin N; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Feb 22; Vol. 6 (4), pp. 1175-1185.
DOI:	10.1182/bloodadvances.2021005492
Abstrakt:	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. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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