Hematopoietic cell transplantation after CD19-directed CAR T-cell therapy for remission consolidation or relapse treatment in pediatric acute lymphoblastic leukemia

Relapse of B-cell acute lymphoblastic leukemia (B-ALL) after CD19-targeted chimeric antigen receptor T-cell therapy (CAR19) remains a substantial challenge. Allogeneic hematopoietic cell transplant (HCT) represents an approach for both post-CAR19 relapse prevention and relapse therapy. However, a paucity of detailed HCT safety and outcome data exists in this population. We conducted a retrospective review of 47 children and young adults with B-ALL who underwent first HCT for post-CAR19 remission consolidation (preemptive cohort, n=26) or relapse therapy (relapse cohort, n=21). With a median follow-up of 4.1 years, 3-year disease-free survival was 90% in the preemptive cohort and 64% in the relapse cohort. Overall survival, cumulative incidence of relapse, and non-relapse mortality at 3 years were 95%, 5%, and 5% in the preemptive cohort, respectively, and 67%, 20%, and 15% in the relapse cohort, respectively. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 14% in the preemptive and 19% in the relapse cohort. Chronic GVHD developed in 24% and 14% of patients alive at 100 days in the preemptive and relapse cohorts, respectively. Veno-occlusive disease/sinusoidal obstruction syndrome was the most common non-GVHD severe organ toxicity, with a cumulative incidence of 10% in the preemptive and 31% in the relapse cohort. In appropriate patients, HCT can be an effective strategy for attaining durable B-ALL remission when used preemptively post-CAR19 or as part of post-CAR19 relapse salvage therapy.

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Publication Details

Journal
Haematologica
Published
2025-11-27
DOI
https://doi.org/10.3324/haematol.2025.288303
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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Hematopoietic cell transplantation after CD19-directed CAR T-cell therapy for remission consolidation or relapse treatment in pediatric acute lymphoblastic leukemia

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CAR-T cell therapy research
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Hematopoietic cell transplantation after CD19-directed CAR T-cell therapy for remission consolidation or relapse treatment in pediatric acute lymphoblastic leukemia

Nancy Bunin, Lisa Wray, Susan McClory, Timothy S. Olson, Jason Lawrence Freedman, Stephen P. Hunger, Susan R. Rheingold, Alix E. Seif, Sarah Mumanachit, Allison Barz Leahy, Shannon L. Maude, Amanda M. DiNofia, Caitlin W. Elgarten, Sarah K. Tasian, Lucy E. Cain, Caroline Diorio, Stephan A. Grupp, Regina M. Myers, Hongyan Liu, Lei Wang, Yimei Li
article en

Abstract

Relapse of B-cell acute lymphoblastic leukemia (B-ALL) after CD19-targeted chimeric antigen receptor T-cell therapy (CAR19) remains a substantial challenge. Allogeneic hematopoietic cell transplant (HCT) represents an approach for both post-CAR19 relapse prevention and relapse therapy. However, a paucity of detailed HCT safety and outcome data exists in this population. We conducted a retrospective review of 47 children and young adults with B-ALL who underwent first HCT for post-CAR19 remission consolidation (preemptive cohort, n=26) or relapse therapy (relapse cohort, n=21). With a median follow-up of 4.1 years, 3-year disease-free survival was 90% in the preemptive cohort and 64% in the relapse cohort. Overall survival, cumulative incidence of relapse, and non-relapse mortality at 3 years were 95%, 5%, and 5% in the preemptive cohort, respectively, and 67%, 20%, and 15% in the relapse cohort, respectively. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 14% in the preemptive and 19% in the relapse cohort. Chronic GVHD developed in 24% and 14% of patients alive at 100 days in the preemptive and relapse cohorts, respectively. Veno-occlusive disease/sinusoidal obstruction syndrome was the most common non-GVHD severe organ toxicity, with a cumulative incidence of 10% in the preemptive and 31% in the relapse cohort. In appropriate patients, HCT can be an effective strategy for attaining durable B-ALL remission when used preemptively post-CAR19 or as part of post-CAR19 relapse salvage therapy.

Haematologica
St. Jude Children's Research Hospital (US), Children's Hospital of Philadelphia (US), Drexel University (US), University of Pennsylvania (US)
Alex's Lemonade Stand Foundation for Childhood Cancer, Pfizer, AstraZeneca, Leukemia and Lymphoma Society, Children's Hospital of Philadelphia, Jazz Pharmaceuticals, LifeArc, Les Laboratories Pierre Fabre, Incyte, Syndax Pharmaceuticals, Servier, Eurostars
Openalex Percentile: Top 49%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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