First name
Julie-An
Middle name
M
Last name
Talano

Title

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

Year of Publication

2022

Number of Pages

1175-1185

Date Published

2022 Feb 22

ISSN Number

2473-9537

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.

DOI

10.1182/bloodadvances.2021005492

Alternate Title

Blood Adv

PMID

34872106

Title

Partially CD3-depleted unrelated and haploidentical donor PSCT has favorable GVHD and survival rates in pediatric hematologic malignancy.

Year of Publication

2019

Date Published

2019 Nov 22

ISSN Number

1523-6536

Abstract

<p>Most children who may benefit from stem cell transplantation lack matched related donors. Alternative donor transplantations with unrelated (URD) or partially matched related donors (PMRD) carry increased risks of graft-versus-host-disease (GVHD) and mortality compared to matched related donor transplants. We hypothesized a strategy of partial CD3/CD19-depletion for URD or PMRD peripheral stem cell transplantation (PSCT) would attenuate risks of GVHD and mortality. We enrolled 84 pediatric patients with hematologic malignancies at the Children's Hospital of Philadelphia and the Children's Hospital of Wisconsin between April 2005 and February 2015 (NCT00579124: https://clinicaltrials.gov/ct2/show/NCT00579124; NCT01071226: https://clinicaltrials.gov/ct2/show/NCT01071226). Two (2.4%) experienced primary graft failure. Relapse occurred in 23 patients (27.4%; cumulative incidence 26.3%), and 17 patients (20.2%) experienced non-relapse mortality (NRM). Grade III-IV acute GVHD was observed in 18 patients (21.4%), and chronic GVHD was observed and graded as limited in 24 (35.3%) and extensive in 8 (11.7%). Three-year OS was 61.8% (95% CI 50.2 -71.4%) and EFS 52.0% (95% CI 40.3 - 62.4%). Age ≥15 years was associated with decreased OS (p=0.05) and EFS (p=0.05). Relapse was more common in children in second complete remission (p=0.03). Partially CD3-depleted alternative donor PSCT NRM, OS, and EFS compare favorably with previously published studies of T cell-replete PSCT. Historically, T cell-replete PSCTs have had a high ratio of extensive compared to limited chronic GVHD, which may explain the comparatively low relapse and NRM rates in our study despite similar overall rates of chronic GVHD. Partial T cell-depletion may expand donor options for children with malignant transplant indications lacking matched related donors by mitigating but not eliminating chronic GVHD.</p>

DOI

10.1016/j.bbmt.2019.11.022

Alternate Title

Biol. Blood Marrow Transplant.

PMID

31765697

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