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    Are mesenchymal stem cells still effective in acute GvHD management?
    (Pergamon-Elsevier Science Ltd, 2025) Ulu, Bahar Uncu; Hindilerden, Ipek Yonal; Yigenoglu, Tugce Nur; Tiryaki, Tarik Onur; Erkurt, Mehmet Ali; Korkmaz, Gulten; Namdaroglu, Sinem
    Objective: Graft-versus-host disease (GvHD) is a common and serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly impacting transplant efficacy. In the treatment of GvHD, numerous therapeutic approaches have been explored, with mesenchymal stem cells (MSCs) emerging as a prominent immunomodulatory option. We aimed to evaluate efficacy and outcomes of using MSCs for steroid refractory acute GVHD (SR-aGvHD) management. Materials and Methods: We retrospectively analyzed data from 36 patients' who received MSCs for treatment of SR-aGvHD following allo-HSCT between 2018 and 2024 from nine transplantation centers in T & uuml;rkiye. The product consisted of umbilical cord-derived allogeneic MSCs, which were administered intravenously. Results: Our cohort was at the median age of 39 years (range: 19-61 years), with aGvHD diagnosed at a median of two months after allo-HSCT. More than half of the patients (58.3%) classified as high-grade aGvHD according to the Minnesota risk scoring. Cord blood-derived MSCs were administered at a median dose of 3.45 (range: 0.8-5) million MSCs/kg, with a median of 3th (range: 2-5) line treatment. The rate of responses exceeding partial response (PR) was approximately 20% at the first month, increasing to 24% at the second month. The six-month survival rate was 33%, with 46% of mortality attributed to sepsis and 12.5% related to GvHD. Multivariate analysis indicated that increasing age (>= 35 years) and lower platelet counts (<= 75 x10(9)/L) were associated with higher mortality (p<0.05). Conclusion: MSC therapy has shown promising potential in improving response rates in aGvHD treatment, with efficacy enhanced by younger age and higher platelet counts.
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    Efficacy of Ruxolitinib in the management of chronic GVHD
    (Pergamon-Elsevier Science Ltd, 2025) Giden, Asli Odabasi; Erkurt, Mehmet Ali; Hindilerden, Ipek Yonal; Hidayet, Emine; Berber, Ilhami; Tiryaki, Tarik Onur; Zorlu, Tugba
    Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematological diseases, with success rates improving due to advancements in conditioning regimens and new anti-graft versus host disease (GVHD) drugs. Ruxolitinib, an oral selective Janus kinase (JAK) 1 and 2 inhibitor has been used to mitigate the effects of various inflammatory and myeloproliferative syndromes, given the JAK kinase pathway's central role in cytokine signaling during inflammatory and immune processes. In this study we aimed to assess ruxolitinib's efficacy in patients with chronic GVHD (cGVHD). Material and methods: This retrospective observational multi-center study involved 50 patients diagnosed with cGVHD after allo-HSCT in Turkey, who were treated with ruxolitinib between April 2018 and March 2024. Results: At the time of initiation of ruxolitinib treatment, most patients had severe cGVHD (n = 29, 58 %). The overall response rate at 6 months of ruxolitinib treatment was observed in 34 patients (68 %), including 6 patients (12 %) with complete responses and 28 patients (56 %) with partial responses, while 7 patients (14 %) experienced treatment failure. ECOG (2-4) performance status was established as an independent risk factor for adverse outcomes [p = 0.029, HR 3.492 (95 % CI: 1.139-10.705)]. At the two-year follow-up, the estimated survival rate was 52 %. Conclusion: Ruxolitinib is safe and effective in the real-world setting for treating cGVHD, showing remission rates comparable to clinical trials. Further research with extended follow-up is necessary to confirm these findings, optimize dosing, and establish the best tapering strategies for responders.
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    What should be the optimal dose of post-transplantation cyclophosphamide for GVHD prophylaxis in allogeneic stem cell transplantation?
    (Pergamon-Elsevier Science Ltd, 2025) Ulas, Turgay; Namdaroglu, Sinem; Hindilerden, Ipek Yonal; Erkurt, Mehmet Ali; Erer, Kerim; Yigenoglu, Tugce Nur; Tiryaki, Tarik Onur
    Objectives: In this study, we aimed to compare the engraftment days, graft versus host disease (GVHD) development, relapse and overall survival (OS) rates in patients using variable intensity conditioning regimens with two different post-transplant cyclophosphamide (PTCy) doses for hematological malignancies. Material and methods: We retrospectively analyzed 162 patients who have had PTCy at a dose of 25 mg/kg x 2 and 50 mg/kg x 2 between 2018 and 2024. Patients were divided in 2 groups; PTCy dose with 25 mg/kg x 2 (Group 1, n = 45) and PTCy dose with 50 mg/kg x 2 (Group 2, n = 117). The engraftment days, GVHD, relapse and OS rates were compared across groups. Results: All patients had myeloablative conditioning regimens and peripheral stem cell collected transplantation. 61.1 % of patients (n = 99) were alive at the end of the study (60 % (n = 27) in Group1 and 61.5 % (n = 72) in Group 2). In Group 1 the median follow-up was 6.9 months and in Group 2 this was 7 months; the median OS was 15.5 months in Group 1 and 49.5 months in Group 2 but this is not statistically significant (Log rank = 0.796). In Group 1, the engraftment times for platelets was 13 days, for neutrophils 17 days; in Group 2, for platelet this was 18 days; and for neutrophils 17 days; this was statistically significant for platelets but not for neutrophil engraftment (p: < 0.001 and p:0.839, respectively). Eighteen patients (40 %) in Group 1 and twenty-seven (23 %) patients in group 2 had acute GVHD (aGVHD). In Group 1 aGVHD rates were higher than Group 2 (p = 0.031). Seven patients (15.5 %) in Group 1 and 6 (5.12 %) patients in group 2 had chronic GVHD (cGVHD). In Group 1 cGVHD rates were also higher than Group 2 (p = 0.048). Twenty-five patients (55.6 %) in Group 1 and 19 patients (16.2 %) in Group 2 had relapsed disease (p < 0.001). Conclusion: Our study showed that there were no differences in survival across the groups. The platelet engraftment time was shorter for the PTCy 25 mg/kg x 2 doses compared to the post-transplantation 50 mg/kg x 2 doses. Both aGVHD and cGVHD rates were higher in 25 mg/kg x 2 dose treated patients. Relapses occurred more commonly with 25 mg/kg x 2 PTCy dose.