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

Allison Barz Leahy, Yimei Li, Julie-An Talano, Caitlin W Elgarten, Alix E Seif, Yongping Wang, Bryon Johnson, Dimitri S Monos, Stephan Kadauke, Timothy S Olson, Jason Freedman, Lisa Wray, Stephan A Grupp, Nancy Bunin, Allison Barz Leahy, Yimei Li, Julie-An Talano, Caitlin W Elgarten, Alix E Seif, Yongping Wang, Bryon Johnson, Dimitri S Monos, Stephan Kadauke, Timothy S Olson, Jason Freedman, Lisa Wray, Stephan A Grupp, Nancy Bunin

Abstract

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.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
LFS and OS by disease type. (A) LFS by type of leukemia, defined as the time from transplantation to relapse or death in the patients who achieved engraftment. (B) LFS by HLA match. (C) LFS by ATG exposure. (D) OS by type of leukemia, defined as the time from transplantation to death from any cause. (E) OS by HLA match. (F) OS by ATG exposure.
Figure 2.
Figure 2.
Cumulative incidence (CI) curves for relapse and NRM, considering each other as competing risks, by disease type. (A) CI curve for relapse. (B) CI curve for NRM.

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