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    Clofarabine, cyclophosphamide, and etoposide (CLOVE) in adult patients with relapsed/refractory acute T-cell lymphoblastic leukemia: single-center experience
    (Cukurova Univ, Fac Medicine, 2023) Güven, Zeynep Tuğba; Tubay, Saziye Esra; Çelik, Serhat; Keklik, Muzaffer; Ünal, Ali
    Purpose: Clofarabine is a second-generation purine analog that inhibits DNA synthesis. It is used as an effective new agent in relapsed refractory acute leukemia. We aimed to report our single center experience about CLOVE protocol as a clofarabine-based regimen in patients with relapsed or refractory T-cell acute lymphoblastic leukemia.Materials and Methods: Thirteen patients with relapsed or resistant T-cell acute lymphoblastic leukemia were included in this study. Patients were administered clofarabine (40 mg/m2/day), etoposide (100 mg/m2/day), and cyclophosphamide (440 mg/m2/day) (5 days chemotherapy). The patients' data were reviewed retrospectively, the demographic and clinical characteristics of patients were recorded.Results: The patients' median age was 47, and 77% (n:10) of them were male. The median number of chemotherapy regimens they received before clofarabine was 3. Of the patients, 54% (n=7) presented with relapse, and 46% (n=6) with refractory disease. Hematological side effects were observed in all patients during treatment, and 4 (31%) patients were complicated by febrile neutropenia. Other side effects were hepatotoxicity 39%, skin reaction 2%, nausea 54%, and mucositis 31%. Three (23%) patients were unresponsive to treatment. A response was obtained in 10 (77%) patients. Allogeneic stem cell transplantation was performed in 4 of 5 patients with complete response. The median follow-up time after CLOVE was 2.3 (0.69- 26.02) months. The median estimated survival time was 21.04 & PLUSMN; 3.88 (95%CI: 13.43-28.64) months. Overall survival was 85.7% at three months and 57.1% at one year. Three patients were alive at the end of our study.Conclusion: The combination of clofarabine, etoposide, and cyclophosphamide (CLOVE) appears to be successful in achieving a response in relapsing or resistant acute leukemia. However, more effective regimens are still needed.
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    Fludarabine-induced bradycardia in allogeneic hematopoietic stem cell transplantation: A retrospective study
    (Sage Publications Ltd, 2024) Celik, Serhat; Guven, Zeynep Tugba; Altinsoy, Abdullah; Tubay, Saziye Esra; Keklik, Muzaffer; Unal, Ali
    Introduction Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. Methods This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. Results Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. Conclusion Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.