Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse.

Cancer Res Treat

Department of Hematology and Oncology, Key laboratory of Pediatric Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Published: July 2022

Purpose: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.

Materials And Methods: CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry.

Results: Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%.

Conclusion: 19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296935PMC
http://dx.doi.org/10.4143/crt.2021.399DOI Listing

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