CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study
| Autor: | Elad Jacoby, Sara Ghorashian, Britta Vormoor, Barbara De Moerloose, Nicole Bodmer, Olga Molostova, Asaf D Yanir, Jochen Buechner, Ronit Elhasid, Bella Bielorai, Srdan Rogosic, Marie-Emilie Dourthe, Michael Maschan, Claudia Rossig, Amos Toren, Arend von Stackelberg, Franco Locatelli, Peter Bader, Martin Zimmermann, Jean Pierre Bourquin, Andre Baruchel |
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| Přispěvatelé: | University of Zurich, Jacoby, Elad, Baruchel, Andre |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Receptors Chimeric Antigen CAR T Adolescent T-Lymphocytes 2720 Hematology Antigens CD19 Hematopoietic Stem Cell Transplantation 610 Medicine & health Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Immunotherapy Adoptive Oncology CD28 Antigens Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA 10036 Medical Clinic Recurrence Humans 2730 Oncology 1306 Cancer Research Child Adaptor Proteins Signal Transducing Retrospective Studies |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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