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, there is a paucity of detailed HCT safety and outcome data 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%, respectively, in the preemptive cohort and 67%, 20%, and 15%, repectively, in the relapse cohort. The cumulative incidence of grade 3-4 acute graft-versus-host disease (GvHD) was 14% in the preemptive cohort 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 cohort and 31% in the relapse cohort. In appropriate patients, HCT can be an effective strategy for attaining durable B-ALL remission when used preemptively after CAR19 or as part of post-CAR19 relapse salvage therapy.