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    What is the role of alpha-1 antitrypsin in the management of acute graft versus host disease?
    (Pergamon-Elsevier Science Ltd, 2025) Yigenoglu, Tugce Nur; Erkurt, Mehmet Ali; Dagdas, Simten; Ulu, Bahar Uncu; Kuku, Irfan; Durdu, Ali; Pepeler, Mehmet Sezgin
    Objective: Acute graft versus host disease (GVHD) occurs in 20-80 % of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of these patients, 40 % will be resistant to steroids, which is the standard first-line approach. There is no standard second line treatment approach for patients with steroid refractory acute GVHD (SR-aGVHD). Alpha-1 antitrypsin is a protease inhibitor and has anti-inflammatory and immune regulatory properties. Here we report the outcomes and safety data of 17 patients treated with alpha-1 antitrypsin for SR-aGVHD. Material and methods: Patients who received at least 2 lines of alpha-1 antitrypsin treatment for SR-aGVHD at five transplant centers in T & uuml;rkiye were included in this retrospective study. Results: The median number of alpha-1 antitrypsin treatment line patients received was 4 (range, 2-5). The median time between alpha-1 antitrypsin administration and response was 65 days (range, 10-138 days). Overall response rate was 70.6 %. When the first- and second-month response rates were compared according to GVHD organ involvement, we found that the response rates were similar in skin, liver and gastrointestinal system involvement (p = 0.281 and p = 0.305, respectively). No grade 3-4 anemia, thrombocytopenia or neutropenia was observed after alpha-1 antitrypsin treatment. Two patients had cytomegalovirus infection and 1 patient had pneumonia. At a median follow-up of 7 months, overall survival was 70.6 % and median overall survival was not reached. Conclusion: In conclusion, alpha-1 antitrypsin is an effective and safe treatment option in patients with SRaGVHD, with response rates of up to 70 % in patients with skin, liver and gastrointestinal system involvement. Larger studies are needed to establish a standard second and subsequent treatment approach in patients with SR-aGVHD.