Unrelated donor α/β T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia. Blood Adv 2022 Feb 22;6(4):1175-1185
Date
12/07/2021Pubmed ID
34872106Pubmed Central ID
PMC8864664DOI
10.1182/bloodadvances.2021005492Scopus ID
2-s2.0-85125302478 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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.
Author List
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 NAuthors
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinJulie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Acute DiseaseAntigens, CD19
Child
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Receptors, Antigen, T-Cell, alpha-beta
Recurrence
T-Lymphocytes
Unrelated Donors
Young Adult
