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CD19/22 CAR T Cell Cocktail Therapy For B-ALL Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation

Posted on:2022-01-21Degree:MasterType:Thesis
Country:ChinaCandidate:N YanFull Text:PDF
GTID:2504306572484434Subject:Blood disease
Abstract/Summary:
Background: B-ALL patients relapsed after allogeneic hematopoietic stem cell transplantation have a poor prognosis and there is no standard approach available currently.Due to the limited efficacy of traditional treatment schemes for relapsed ALL post-HSCT,disease recurrence is the main cause of mortality.Therefore,there is an urgent need for the safe and effective new treatment for this subgroup of patients.Chimeric antigen receptor(CAR)T cells induce high rates of initial response and long-term remissions among patients with B-cell malignancies,especially B-ALL.Different to physiologic T cell receptors(TCR),CARs act in an MHC-independent manner with an extracellular antigen-specific recognition domain,which provide a new promising approach for this subgroup of patients.Meanwhile,sequential infusion of anti-CD22 and anti-CD19 CAR-T cells has been proved to be effective in preventing recurrence caused by loss of target antigen,which partly improve the prognosis of patients.So this study retrospectively analyzed the efficacy,safety and related factors of sequential infusion of CAR19/22 T cells in ALL patients with relapsed after transplantation.Method: From July 2016 to July 2020,23 patients with relapsed acute lymphoblastic leukemia who received sequential infusion of CAR19/22 T cells post HSCT were included in this study,including 9 donor-derived and 14 recipient--derived.All patients received at least one line post relapse treatment including withdrawal of immunosuppressive agents,infusion of donor lymphocytes or salvage chemotherapy before CAR-T infusion.Result: In this study,except for one patient who refused to be evaluated,the remaining22 patients achieved MRD negative complete remission within 30 days after CAR-T infusion.After sequential infusion of CAR19/22 T cells,there were 20 cases of CRS,4 cases of neurotoxicity,7 cases of GVHD and 5 cases of severe infection.Most of the toxicities were slight and reversible.One year overall survival(OS)and progression free survival(PFS)were72.0% ± 10.7% and 55.8% ± 11.9%,respectively.Early recurrence after transplantation,GVHD or severe infection after CAR-T infusion were the poor prognostic factors.Conclusion: Sequential infusion of CAR19/22 T cells is safe and effective in the treatment of relapsed ALL patients after HSCT...
Keywords/Search Tags:Allogeneic hematopoietic stem cell transplantation, Chimeric antigen receptor T-cell, Acute lymphoblastic leukemia, Relapse, CAR19, CAR22
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