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• W3204237128 abstract "A potent graft-versus-leukemia (GVL) response is crucial in preventing relapse, the major impediment to successful allogeneic hematopoietic cell transplantation (HCT). In preclinical studies, type 1 interferon (IFN-α) enhanced cross-presentation of leukemia-specific antigens by CD8α dendritic cells (DCs) and amplified GVL. This observation was translated into a proof-of-concept phase 1/2 clinical trial with long-acting IFN-α (pegylated IFN-α [pegIFNα]) in patients undergoing HCT for high-risk acute myeloid leukemia (AML). Patients with treatment-resistant AML not in remission or those with poor-risk leukemia were administered 4 dosages of pegIFNα every 14 days beginning at day -1 before HCT. Dose selection was established by adaptive design that continuously assessed the probability of dose-limiting toxicities throughout the trial. Efficacy was evaluated by determining the 6-month incidence of relapse at the maximum tolerated dose (MTD). Thirty-six patients (median age, 60 years) received pegIFNα treatment. Grade 3 or greater severe adverse events occurred in 25% of patients, establishing 180 μg as the MTD. In phase 2, the incidence of relapse was 39% at 6 months, which was sustained through 1-year post-HCT. The incidence of transplant-related mortality was 13%, and severe grade III-IV acute graft-versus-host disease (GVHD) occurred in 11%. Paired blood samples from donors and recipients after HCT revealed elevated levels of type 1 IFN with cellular response, the persistence of cross-presenting DCs, and circulating leukemia antigen-specific T cells. These data suggest that prophylactic administration of pegIFNα is feasible in the peri-HCT period. In high-risk AML, increased toxicity was not observed with preliminary evidence for reduction in leukemia relapse after HCT. This trial was registered at www.clinicaltrials.gov as #NCT02328755." @default.
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• W3204237128 date "2021-12-03" @default.
• W3204237128 modified "2023-10-14" @default.
• W3204237128 title "Type 1 interferon to prevent leukemia relapse after allogeneic transplantation" @default.
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• W3204237128 doi "https://doi.org/10.1182/bloodadvances.2021004908" @default.
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