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Item Comparable Survival Using A CMV-Matched Or A Mismatched Donor For CMV Plus Patients Undergoing T-Replete Haplo-HSCT With PT-Cy For Acute Leukemia: A Study Of Behalf Of The Infectious Diseases And Acute Leukemia Working Parties Of The EBMT(2018) Cesaro, Simone; Crocchiolo, Roberto; Tridello, Gloria; Knelange, Nina; Van Lint, Maria Teresa; Koc, Yener; Ciceri, Fabio; Gulbas, Zafer; Tischer, Johanna; Afanasyev, Boris; Bruno, Benedetto; Castagna, Luca; Blaise, Didier; Mohty, Mohamad; Irrera, Giuseppe; Diez-Martin, J. L.; Pierelli, Luca; Pioltelli, Pietro; Arat, Mutlu; Delia, Mario; Fagioli, Franca; Ehninger, Gerhard; Aljurf, Mahmoud; Carella, Angelo Michele; Ozdogu, Hakan; Mikulska, Malgorzata; Ljungman, Per; Nagler, Arnon; Styczynski, Jan; https://orcid.org/0000-0002-8902-1283; 29330396; AAD-5542-2021The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+P/R+ and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI: 50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other main outcomes were comparable. No difference in NRM nor OS was observed after stratification for the intensity of conditioning and multivariate anaysis confirmed the lack of significant association with NRM or OS. In conclusion, the choice of a CMV-seronegative donor did not impair early survival of CMV-seropositive patients with acute leukemia after a first, non T-cell depleted haploidentical HSCT and PT-Cy among this series of 983 consecutive patients. Future research may focus on the assessment of the hierarchy of all the donor variables.Item Comparative study of treosulfan plus Fludarabine (FT14) with busulfan plus Fludarabine (FB4) for acute myeloid leukemia in first or second complete remission: An analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP)(2022) Gavriilaki, Eleni; Labopin, Myriam; Sakellari, Ioanna; Salmenniemi, Urpu; Yakoub-Agha, Ibrahim; Potter, Victoria; Berceanu, Ana; Rambaldi, Alessandro; Hilgendorf, Inken; Kroeger, Nicolaus; Mielke, Stephan; Zuckerman, Tsila; Sanz, Jaime; Busca, Alessandro; Ozdogu, Hakan; Anagnostopoulos, Achilles; Savani, Bipin; Giebel, Sebastian; Bazarbachi, Ali; Spyridonidis, Alexandros; Nagler, Arnon; Mohty, Mohamad; 36138068Different doses of treosulfan plus fludarabine have shown advantage over reduced intensity regimens. However, data comparing higher doses of treosulfan to myeloablative busulfan are limited. Thus, we compared outcomes between FT14 (fludarabine 150/160 mg/m(2) and treosulfan 42 g/m(2), or FT14) over FB4 (fludarabine 150/160 mg/m(2) and busulfan 12.8 mg/kg). We retrospectively studied patients from European Society for Blood and Marrow Transplantation registry: a) adults diagnosed with acute myeloid leukemia (AML), b) recipients of first allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated or sibling donor (2010-2020), c) HSCT at first or second complete remission, d) conditioning with FT14 or FB4. FT14 recipients (n = 678) were older, with higher rates of secondary AML, unrelated donors, peripheral blood grafts, and adverse cytogenetics, but lower percentage of female donor to male recipient compared to FB4 (n = 2025). Analysis was stratified on age. In patients aged < 55 years, FT14 was associated with higher relapse incidence (RI) and lower Leukemia-Free Survival (LFS). In patients aged >= 55 years, acute GVHD CI was higher in FB4, without significant differences in other outcomes. Although FT14 has been used for higher-risk HSCT patients, our large real-world multicenter study suggests that FB4 is associated with better outcomes compared to FT14 in younger patients.Item Evolution of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in turkey: a multicenter retrospective analysis(2021) Karadag, Fatma Keklik; Yenerel, Mustafa Nuri; Yilmaz, Mehmet; Uskudar, Hava; Ozkocaman, Vildan; Tuglular, Tulin Firatli; Erdem, Fuat; Unal, Ali; Ayyildiz, Orhan; Ozet, Gulsum; Comert, Melda; Kaya, Emin; Ayer, Mesut; Salim, Ozan; Guvenc, Birol; Ozdogu, Hakan; Mehtap, Ozgur; Sonmez, Mehmet; Guler, Nil; Hacioglu, Sibel; Aydogdu, Ismet; Bektas, Ozlen; Toprak, Selami Kocak; Kaynar, Lale; Yagci, Munci; Aksu, Salih; Tombak, Anil; Karakus, Volkan; Yavasoglu, Irfan; Onec, Birgul; Ozcan, Mehmet Ali; Undar, Levent; Ali, Ridvan; Ilhan, Osman; Saydam, Guray; Sahin, Fahri; 34322292Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.Item Excellent outcomes of allogeneic transplantation from peripheral blood of HLA-matched related donors for adult sickle cell disease with ATLG and posttransplant cyclophosphamide-containing regimen: an update work(2020) Ozdogu, Hakan; Boga, Can; Yeral, Mahmut; Kozaoglu, Ilknur; Gereklioglu, Cigdem; Aytan, Pelin; Kasar, Mutlu; Asma, Suheyl; Buyukkurt, Nurhilal; Korur, Asli; Sariturk, Cagla; 0000-0002-0895-4787; 0000-0001-5335-7976; 0000-0002-5086-5593; 0000-0003-3856-7005; 0000-0002-8902-1283; 0000-0002-5268-1210; 0000-0002-9580-628X; 0000-0002-9680-1958; 31992850; AAL-6544-2020; AAE-1457-2021; AAS-7129-2021; ABC-4148-2020; AAI-7831-2021; AAD-5616-2021; AAL-3906-2021; AAD-5542-2021; AAE-1241-2021; AAD-6222-2021Item Problems With Unrelated Donors For Stem Cell Transplant and Proposed Solutions: A Single-Center Experience(2020) Kozanoglu, Ilknur; Ozdogu, Hakan; Asma, Suheyl; Yeral, Mahmut; Atar, Sevtap; Tepebasi, Songul; Cuhadar, Mediha Has; Ozturk, Murat; Boga, Can; 0000-0001-5335-7976; 0000-0002-5268-1210; 0000-0002-8902-1283; 0000-0002-9680-1958; 0000-0002-9580-628X; 29790459; ABC-4148-2020; AAI-7831-2021; AAE-1241-2021; AAD-5542-2021; AAD-6222-2021Item Significance of Lymphocyte Count, Monocyte Count, and Lymphocyte-To-Monocyte Ratio in Predicting Molecular Response in Patients with Chronic Myeloid Leukemia: a Single-Centre Experience(2020) Pepedil-Tanrikulu, Funda; Buyukkurt, Nurhilal; Korur, Asli; Sariturk, Cagla; Aytan, Pelin; Boga, Can; Ozdogu, Hakan; Kozanoglu, Ilknur; 0000-0002-5268-1210; 0000-0002-0895-4787; 0000-0002-8902-1283; 0000-0002-5086-5593; 0000-0002-9680-1958; 32162884; AAE-1241-2021; AAD-6222-2021; AAE-1457-2021; AAD-5542-2021; AAD-5616-2021Background: Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. Methods: Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. Results: A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. Conclusions: ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.Item The Impact of the Ferric Carboxymaltose on Hemoglobin and Ferritin Levels(2020) Korur, Asli; Gereklioglu, Cigdem; Asma, Suheyl; Aytan, Pelin; Tanrikulu, Funda P.; Solmaz, Soner; Kasar, Mutlu; Buyukkurt, Nurhilal; Yeral, Mahmut; Boga, Can; Ozdogu, Hakan; 0000-0003-3856-7005; 0000-0002-8902-1283; 0000-0002-5086-5593; 0000-0002-0895-4787; 0000-0001-5335-7976; 0000-0002-9580-628X; 0000-0002-9680-1958; 32776750; AAD-6222-2021; AAL-3906-2021; AAD-5542-2021; AAD-5616-2021; AAE-1457-2021; ABC-4148-2020; AAI-7831-2021Background: Anemia is a frequent disorder worldwide. Iron deficiency anemia (IDA) is the most common form of anemia. Although oral iron is the first choice for treatment, the efficacy of oral iron preparations may be limited. Ferric carboxymaltose (FCM) is a novel parenteral iron preparation which can rapidly replenish iron stores. The aim of the present study is to investigate the impact of FCM dose on hemoglobin (Hb) and ferritin levels and the frequency of hypersensitivity reactions. Methods: This study was conducted with 765 IDA patients between September 1, 2016 and September 1, 2018. Hemoglobin (Hb), serum ferritin, transferrin saturation values were examined at the time of diagnosis, Hb and ferritin values at first month. Results: Post-treatment Hb and ferritin levels significantly increased. The mean Hb level alteration was 2.43 +/- 1.2 g/dL, the median ferritin level alteration was 157.3 ng/mL. The mean Hb level was lower and the mean change in Hb level was higher in higher doses. Allergic reactions were more frequent in higher doses. Conclusions: Ferric carboxymaltose is a novel treatment option with a low risk of hypersensitivity reactions and well tolerated even in high doses.Item Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG)(2020) Ozdogu, Hakan; 0000-0002-8902-1283; 32522474; AAD-5542-2021Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15 - 71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF +, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.Item Total body irradiation plus fludarabine compared to busulfan plus fludarabine as "reduced-toxicity conditioning" for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT(2020) Ozdogu, Hakan; 0000-0002-8902-1283; 32892216; AAD-5542-2021The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients <50 years old, TBI8Gy/Flu was associated with improved LFS (hazard ratio (HR) = 0.5,p = 0.04), OS (HR = 0.31,p = 0.004), and survival free from both graft-versus-host disease and relapse (HR = 0.55,p = 0.03), as well as tendency to reduced risk of relapse (HR = 0.53,p = 0.08). Among patients aged 50 years or older the use of TBI8Gy/Flu was associated with increased incidence of NRM (HR = 3.9,p = 0.0009), with no significant impact on other outcome measures. We conclude that the use of TBI8Gy/Flu as "reduced-toxicity" regimen may be advised in younger patients with AML referred for allo-HCTItem Post-transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA-identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation(2020) Ozdogu, Hakan; 0000-0002-8902-1283; 33119152; AAD-5542-2021BACKGROUND Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addition of antithymocyte globulin (ATG) or post-transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. METHODS We compared the outcomes of adults with acute myeloid leukemia undergoing allo-HSCT from HLA-identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). RESULTS Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02). CONCLUSION PTCY is feasible in an HLA-identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.