Anti-CD19-CAR T-Cell from Patients Relapsed after Allo-HSCT with a Low Level of Donor Chimerism Restored to Complete Donor Chimerism: Successful Cases and Analysis

Purpose: To study the efficacy of anti-CD19-CAR T-cell therapy and the changes of donor chimerism in CAR-T cells in vitro culture for patients who relapsed after allo-HSCT with a low level of donor chimerism. Methods: Two patients relapsed after allo-HSCT with a low level of donor chimerism (11.22%...

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Bibliographic Details
Published in:Blood Vol. 134; no. Supplement_1; p. 5628
Main Authors: Li, Qing, Mu, Juan, Yang, Zhen-xing, Mou, Nan, Wang, Jia, Yuan, Ji-jun, Jiang, Yanyu, Juanxia, Meng, Deng, Qi
Format: Journal Article
Language:English
Published: Elsevier Inc 13-11-2019
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Summary:Purpose: To study the efficacy of anti-CD19-CAR T-cell therapy and the changes of donor chimerism in CAR-T cells in vitro culture for patients who relapsed after allo-HSCT with a low level of donor chimerism. Methods: Two patients relapsed after allo-HSCT with a low level of donor chimerism (11.22% and 16.08%). Their autologous PBMCs were selected for anti-CD19-CAR T-cell therapy because their sibling or unrelated donor could not provide PBMC cells. The adverse events (AEs) were observed after CAR T-cell infusion. The cytokine release syndrome (CRS), the expansion of anti-CD19-CAR T-cells, the DNA level of anti-CD19-CAR gene and the changes of the donor chimerism were detected after CAR T-cell infusion. Then we selected other 7 acute leukemia patients relapsed after allo-HSCT with a low level of donor chimerism to detect the changes of donor chimerism in their T cells and anti-CD19-CAR T-cells in vitro culture. Results: Their notable AEs were grade 2 CRS. They had no aGVHD during anti-CD19-CAR T-cell therapy. They achieved CR 14 days after anti-CD19-CAR T-cell therapy with a restoration of complete donor chimerism (98.61% and 98.48%). To date, they had leukemia-free survival (LFS) and complete donor chimerism for 8 and 7 months. It was very interesting and fortunate that the CAR-T cells infused into the two patients were restorated to complete donor chimerism (99.2% and 99.4%). Then we found that complete donor chimerism were restored after 12 days culture in vitro in all the T cells and anti-CD19-CAR T-cells in the other 7 patients relapsed after allo-HSCT with a low level of donor chimerism. Conclusions: Anti-CD19-CAR T-cells derived from patients relapsed after allo-HSCT with a low level of donor chimerism were effective for this salvage therapy and could restorate to complete donor chimerism after 12 days culture in vitro. [Display omitted] No relevant conflicts of interest to declare.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2019-127850