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Öğe 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 YonalIn 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.Öğe 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, SinemObjective: 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.Öğe Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies(Galenos Yayincilik, 2022) Bozdag, Sinem Civriz; Seval, Guldane Cengiz; Hindilerden, Ipek Yonal; Hindilerden, Fehmi; Andic, Neslihan; Baydar, Mustafa; Kaynar, Lale AydinObjective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARSCoV-2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixtynine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.Öğe 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, TugbaObjectives: 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.Öğe Extracorporeal photopheresis in steroid-refractory chronic graft-versus-host disease: A retrospective multicenter study(Pergamon-Elsevier Science Ltd, 2021) Dal Sinan, Mehmet; Batgi, Hikmettullah; Erkurt, Mehmet Ali; Hindilerden, Ipek Yonal; Kuku, Irfan; Kurtoglu, Erdal; Kaya, EminBackground and objectives: Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients. Materials and methods: In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system. Results: Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1-261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients. Conclusions: ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD.Öğe Extracorporeal photopheresis in the treatment of acute graft-versus-host disease: A multicenter experience(Pergamon-Elsevier Science Ltd, 2021) Batgi, Hikmettullah; Dal, Mehmet Sinan; Erkurt, Mehmet Ali; Kuku, Irfan; Kurtoglu, Erdal; Hindilerden, Ipek Yonal; Kaya, EminBackground and objectives: Extracorporeal photopheresis (ECP) is one of the second-line treatment strategies in steroid-refractory acute graft-versus-host disease (aGvHD). We aimed to share our multicenter experience using ECP in our steroid-refractory aGvHD patients. Materials and methods: A retrospective observational series of 75 aGvHD patients from 4 transplant centers were analyzed. All ECP procedures were performed with the off-line system. All patients received ECP as second-line therapy. Results: 74.7 % of aGvHD patients were grade 3 or 4. The overall response rate was 42.7 % (32/75) in aGvHD including 17 complete responses (22.7 %). Median follow-up was 6 months (range, 1-68). Median overall survival (OS) was 5 months for non-responders and 68 months for responders (p < 0.001). Twenty-seven (36 %) patients are alive, and 48 (64 %) patients have died. Conclusions: Early initiated ECP could be an effective treatment alternative in patients with steroid-refractory aGvHD.Öğe Outcomes of Brentuximab Vedotin Monotherapy in Refractory/Relapsed Classical Hodgkin's Lymphoma: A Multi-Center Retrospective Study on Survival and Safety(Springer India, 2025) Bakirtas, Mehmet; Hindilerden, Ipek Yonal; Ulu, Bahar Uncu; Ekinci, Omer; Dogu, Mehmet Hilmi; Aydogdu, Ismet; Berber, IlhamiBackground Refractory/relapsed classical Hodgkin's lymphoma (R/RcHL) poses significant treatment challenges, with limited success rates in achieving long-term remission. Brentuximab Vedotin (BV), an anti-CD30 monoclonal antibody-drug conjugate, has emerged as a promising therapeutic option. This study aims to evaluate the efficacy and safety of BV monotherapy in R/RcHL patients, particularly regarding survival outcomes and adverse events. Methods This multi-center retrospective study included 82 R/RcHL patients aged 18 and over, treated with BV monotherapy across 14 institutions in Turkey from June 2012 to June 2020. Data on demographics, clinical characteristics, treatment response, adverse events, and overall survival (OS) rates were collected and analyzed. Primary outcomes were overall treatment response rate and OS, while the secondary outcome focused on the adverse event profile of BV treatment. Results Among the patients (56.1% female, median age 33.5 years), the overall treatment response rate was 76.8%. The median OS was 13.6 months, with patients undergoing hematopoietic stem cell transplantation (HSCT) post-BV treatment exhibiting significantly longer survival (19.6 months) compared to those who did not receive HSCT (7.8 months, p < 0.001). Grade 3 to 5 adverse events were observed in 32.9% of patients, with neutropenia being the most common. Conclusion BV monotherapy demonstrates substantial efficacy in treating R/RcHL, offering a favorable balance between treatment response and manageable adverse events. Particularly effective as a bridging therapy to HSCT, BV significantly extends survival in R/RcHL patients. These findings underscore the need for prospective studies to further delineate patient subsets most likely to benefit from BV monotherapy.Öğe Real-World Efficacy and Safety of Ruxolitinib in Steroid-Refractory Graft-Versus-Host Disease: A Multicenter Retrospective Study From Turkey(Cig Media Group, Lp, 2025) Bakirtas, Mehmet; Berber, Lhami; Hindilerden, Ipek Yonal; Dal, Mehmet Sinan; Guner, Sebnem Izmir; Uysal, Ayse; Ekinci, Omer[No abstract available]Öğe The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL(Cig Media Group, Lp, 2022) Akpinar, Seval; Dogu, Mehmet Hilmi; Celik, Serhat; Ekinci, Omer; Hindilerden, Ipek Yonal; Dal, Mehmet Sinan; Davulcu, Eren ArslanWe evaluated the safety and efficacy of single-agent ibrutinib in 200 patients presenting with relapsed/refractory CLL in real-world settings. With an estimated median OS of 52 months, 146 patients (75%) achieved at least PR; 16 (8.7%) patients discontinued ibrutinib due to adverse events. The results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice. Introduction/Background: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. Patients/Methods: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the par ticipating centers. Results: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+ /p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were >= grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atr ial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare dur ing the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. Conclusion: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice. (C) 2021 Elsevier Inc. All rights reserved.Öğe Real-World Outcomes of Ruxolitinib as Salvage Therapy in Steroid-Refractory Acute and Chronic Graft-Versus-Host Disease: A Multicenter Retrospective Observational Study from Turkey(Mdpi, 2026) Bakirtas, Mehmet; Berber, Ilhami; Hindilerden, Ipek Yonal; Dal, Mehmet Sinan; Izmir Guner, Sebnem; Uysal, Ayse; Ekinci, OmerIntroduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017-2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 +/- 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory.Öğe The effect of threosulfan-based versus busulfan-based preparation regimens on transplant outcomes(Pergamon-Elsevier Science Ltd, 2025) Candir, Burcu Aslan; Okumus, Nazik; Hindilerden, Ipek Yonal; Erkurt, Mehmet Ali; Namdaroglu, Sinem; Merter, Mustafa; Yilmaz, SedaBackground: Allogeneic hematopoietic stem cell transplantation is a curative therapy for malignant and nonmalignant hematologic disorders. Conditioning regimens, such as those based on busulfan, are utilized to promote engraftment. Busulfan-based regimens are commonly employed but exhibit significant toxicity, leading to interest in alternate drugs such as treosulfan, which may offer a superior safety profile while preserving efficacy. Methods: This retrospective study examined 240 adult patients diagnosed with acute myeloid leukemia or acute lymphoblastic leukemia who received allogeneic hematopoietic stem cell transplantation at nine transplantation centers in T & uuml;rkiye from 2010 to 2024. Patients underwent either a busulfan-based or treosulfan-based conditioning regimen. Results: Engraftment was effective in both groups, with neutrophil engraftment happening earlier in the busulfan group (13 days vs. 15 days, p = 0.001). The incidence of veno-occlusive disease was significantly higher in the busulfan group (10.1 % vs. 0.9 %, p = 0.002). Cytomegalovirus infections were more prevalent in the busulfan group (51.2 % vs. 26.1 %, p < 0.001). Acute graft versus host disease occurred more frequently in the busulfan group (27.9 % vs. 18.9 %, p = 0.128); nonetheless, this difference did not reach statistical significance. No significant differences in relapse rates were detected through the groups. The overall survival was not reached in the busulfan group, while the treosulfan group demonstrated an overall survival of 40 months. Conclusion: Treosulfan-based conditioning regimens demonstrate similar efficacy to busulfan-based regimens while presenting a more acceptable toxicity profile. Treosulfan-based regimens also show a lower occurrence of veno-occlusive disease and cytomegalovirus infections.Öğe The impact of second allogeneic hematopoietic stem cell transplantation as salvage therapy for hematologic diseases after a first allogeneic transplantation(Pergamon-Elsevier Science Ltd, 2025) Batgi, Hikmetullah; Zorlu, Tugba; Erkurt, Mehmet Ali; Uzay, Ant; Hindilerden, Ipek Yonal; Pepeler, Mehmet Sezgin; Apaydin, MerveBackground and objectives: Acute leukemia patients who relapse after the first allogeneic stem-cell transplantation (HSCT1) have a poor prognosis. Second allogeneic hematopoietic stem-cell transplantation (HSCT2) is a therapeutic option for patients with acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) relapsing after HSCT1. Our aim is to evaluate the efficacy of HSCT2 in acute leukemia patients who relapsed after HSCT1. Material and methods: In the current study, we retrospectively analyzed the data of 72 patients who underwent HSCT2. Forty-six patients with AML and 26 patients with ALL were included in the study. Results: Before undergoing HSCT2, 47 % of patients were in complete remission. Median follow-up was 8 (1-109) months. Mortality at last follow-up was 61.1 %, and the median overall survival was 11 months (95 % CI: 1-22.9). Univariate analysis identified that age, Eastern Cooperative Oncology Group (ECOG), Body Mass Index, chimerism, conditioning regimen, CD34+ infused cell count, post-transplant cyclophosphamide usage, disease type, pre transplant hemoglobin-lymphocyte-lactate dehydrogenase-ferritin might be significant factors. After multivariate analysis ECOG (HR: 2.142; 95 % CI: 1.061-4.326; p = 0.034) was the only independent predictor for survival. Conclusion: HSCT2 remains a feasible but high-risk treatment option for patients with relapsed acute leukemia after HSCT1. Our findings confirm that ECOG performance status is a key determinant of survival despite advances in transplantation techniques.Öğe 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 OnurObjectives: 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.
