Journal
BONE MARROW TRANSPLANTATION
Volume 56, Issue 2, Pages 376-386Publisher
SPRINGERNATURE
DOI: 10.1038/s41409-020-01027-6
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Funding
- Plan Nacional de I + D+ I [PI15/01094, PFIS0200 (AC16/00025), PI18/00223, FI19/00208]
- ISCIII-Subdireccion General de Evaluacion y Formento de la Investigacion Sanitaria
- Fondo Europeo de Desarrollo Regional (FEDER)
- Subvencions per a la Intensificacio Facultatius Especialistes del Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020 [SLT006/17/00199]
- 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation
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BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and less impairment of IgA, suggesting the possibility of an immune reservoir. Persistent B-cell dysfunction might persist after CART19 loss in this population.
CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9-24.9). Median follow-up after infusion was 7.1 months (0.5-42). BCA was observed 7 days after infusion (3-8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41-99) and 13% undetectable IgA levels at 185 days (11-308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.
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