CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study.
Adaptor Proteins, Signal Transducing
Adolescent
Antigens, CD19
CD28 Antigens
Child
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunotherapy, Adoptive
/ adverse effects
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ etiology
Receptors, Chimeric Antigen
Recurrence
Retrospective Studies
T-Lymphocytes
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
23
06
2021
accepted:
11
03
2022
revised:
01
03
2022
pubmed:
27
4
2022
medline:
7
6
2022
entrez:
26
4
2022
Statut:
ppublish
Résumé
Relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may occur in the central nervous system (CNS). Most clinical trials of CAR T-cell therapy excluded patients with active CNS leukemia, partially for concerns of neurotoxicity. Here, we report an international study of fifty-five children and adolescents who received CAR T-cell therapy for relapsed BCP-ALL with CNS involvement at the time of referral. All patients received bridging therapy, 16 still having active CNS disease at the time of lymphodepletion. Twelve patients received CD28-based CAR T-cells, 9 being subsequently treated with allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Forty-three patients received 4-1BB-based CAR T-cells. Cytokine-release syndrome (CRS) and neurotoxicity occurred in 65% and 38% of patients, respectively, more frequently following treatment with CD28-based CARs. Fifty-one of 54 evaluable patients (94%) achieved complete response following this therapy. Relapse occurred in 22 patients: 19/43 following 4-1BB-based CARs (12 CNS relapses), and 3/12 after CD28-based CARs with subsequent HSCT (no CNS relapse). Patients treated with tisagenlecleucel for an isolated CNS relapse had a high incidence of a subsequent CNS relapse (6 of 8). CAR T-cells were found to be effective in this cohort, though the risk of CNS relapse was not completely mitigated by this approach.
Identifiants
pubmed: 35468946
doi: 10.1038/s41375-022-01546-9
pii: 10.1038/s41375-022-01546-9
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antigens, CD19
0
CD28 Antigens
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1525-1532Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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