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    Anti-T lymphocyte globulin plus posttransplant cyclophosphamide 25 mg/kg versus posttransplant cyclophosphamide 50 mg/kg in patients with acute leukemias
    (Springernature, 2025) Karakus, Abdullah; Toptas, Tayfur; Dal, Mehmet Sinan; Durdu, Ali; Hatipoglu, Ugur; Kayer, Merve Apaydin; Hindilerden, Ipek Yonal
    In this study, we aimed to compare the engraftment days, graft-versus-host disease (GVHD) development, relapse and overall survival rates in patients using myeloablative/reduced intensity conditioning regimens with posttransplant cyclophosphamide (PTCy) 25 mg/kg x2 with Anti-T lymphocyte Globulin (ATLG) (n = 29) and PTCy 50 mg/kg x2 doses (n = 41) in patients with acute leukemias. Matched related, matched unrelated, 1 mismatched unrelated, and haploidentical donors were selected for the patients. Platelet (median 11 vs 17 days) and neutrophil (median 14 vs 15 days) engraftment times were shorter in ATLG+ PTCy25 treated patients (both p < 0.05); veno-occlusive disease rates, graft failure and poor graft functions were similar between the two approaches (all p > 0.05); cumulative incidences of grade II-IV aGVHD at +100 days, grade III-IV aGVHD at +100 days, and grade II-IV cGVHD at 1-year were comparable between ATLG+PTCy25 and PTCy50 groups (all p > 0.05). Cumulative incidences of relapse and non-relapse mortality at 1-year were similar in two cohorts (both p > 0.05). PTCy50 was associated with a statistically significant benefit in terms of GVHD-free/relapse-free survival (GRFS) at 1-year (p = 0.03). Median GRFS was 115 (95% CI: 42-214) days and 248 (95% CI: 151-not reached) days, respectively [HR was 0.51 (0.28-0.95), p = 0.03; GRFS at 1-year was 20.7% vs 44.3%, respectively]. However, the groups were comparable in terms of PFS and OS. Median PFS was 332 days (95% CI: 182 days-not reached) for ATLG+PTCy25 group. It was not reached (95% CI: 210 days-not reached) for the patients who received PTCy50. Median OS was not reached in either ATLG+PTCy25 (95% CI: 191 days-not reached) or PTCy50 groups (Log rank = 0.42). Our study showed that lowering PTCy dose with ATLG seems to accelerate platelet and neutrophil engraftment rates; confers similar survival and relapse rates, similar acute and chronic GVHD frequency despite increased GRFS at 1-year.
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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.