Long-term follow-up of patients with relapsed b-ALL after allo-HSCT treated with CD19 CAR-T cell from recipients and donors

Abstract

Abstract Background: Acute lymphoblastic leukemia (B-ALL) patients who relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) had a very poor prognosis. Donor-derived anti-CD19 CAR-T cell therapy had shown surprising effects in these patients. But some donors could not provide their peripheral blood mononuclear cells (PBMCs) for donor-derived anti-CD19 CAR-T cell therapy. Patients and methods: This study aimed to evaluate the clinical outcomes of anti-CD19 CAR-T cell therapy in 23 relapsed B-ALL patients who relapsed after allo-HSCT between January 2019 and March 2024 were enrolled. Since some donors of allo-HSCT unable to provide peripheral blood mononuclear cells (PBMCs) for CAR-T cell therapy, they were divided into two groups: Recipient group (R group) and Donor group (D group). The clinical response, donor chimerism analysis, adverse events (AEs), levels of CAR-T cell and interleukin-6 (IL-6), graft versus acute host disease (aGVHD) were observed in our study. Results: There was no difference of detailed characteristics in two groups. The donor chimerism rate of all the CAR-T cells in R group resumed to 99.31±0.32% on infusion day. There was no difference of the complete response (CR)/CR with incomplete count recovery (Cri) rates in two groups at 28 days post CAR-T cell infusion. Survival analysis indicated that the R group showed better progression-free survival (PFS) and overall survival (OS) rates than D group 12 months after anti-CD19 CAR-T cell therapy. There was no difference in the median peak of CAR-T cells in two groups, but the peak time was earlier in D group than that of in R group. The median peak of IL-6 was higher in D group than that of in R group, and the peak time was earlier in D group than that of in R group also. There was no difference of the CRS or ICANS grades in two groups. And there was no difference of the grades of neutropenia, anemia or thrombocytopenia in these two groups. There was no difference of grades of aGVHD between two groups also.Conclusion: Recipient-derived anti-CD19 CAR-T cell therapy might be an effective salvage therapies for patients with B-ALL who relapsed after allo-HSCT.