دورية أكاديمية
أعرض في EDS

Fludarabine exposure in the conditioning prior to allogeneic hematopoietic cell transplantation predicts outcomes.

التفاصيل البيبلوغرافية
العنوان: Fludarabine exposure in the conditioning prior to allogeneic hematopoietic cell transplantation predicts outcomes.
المؤلفون: Langenhorst JB; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Laboratory of Translational Immunology and., van Kesteren C; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands., van Maarseveen EM; Department of Clinical Pharmacy, University Medical Centre Utrecht (UMCU), Utrecht University, Utrecht, The Netherlands., Dorlo TPC; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands., Nierkens S; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Laboratory of Translational Immunology and., Lindemans CA; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands., de Witte MA; Laboratory of Translational Immunology and.; Department of Hematology, UMCU, Utrecht University, Utrecht, The Netherlands; and., van Rhenen A; Department of Hematology, UMCU, Utrecht University, Utrecht, The Netherlands; and., Raijmakers R; Department of Hematology, UMCU, Utrecht University, Utrecht, The Netherlands; and., Bierings M; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands., Kuball J; Laboratory of Translational Immunology and.; Department of Hematology, UMCU, Utrecht University, Utrecht, The Netherlands; and., Huitema ADR; Department of Clinical Pharmacy, University Medical Centre Utrecht (UMCU), Utrecht University, Utrecht, The Netherlands.; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands., Boelens JJ; Pediatric Blood and Marrow Transplant Program, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Stem Cell Transplant and Cellular Therapies, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
المصدر: Blood advances [Blood Adv] 2019 Jul 23; Vol. 3 (14), pp. 2179-2187.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Hematopoietic Stem Cell Transplantation*/adverse effects , Hematopoietic Stem Cell Transplantation*/methods , Transplantation Conditioning*/adverse effects , Transplantation Conditioning*/methods, Myeloablative Agonists/*therapeutic use , Vidarabine/*analogs & derivatives, Adolescent ; Adult ; Cause of Death ; Female ; Humans ; Male ; Middle Aged ; Mortality ; Myeloablative Agonists/administration & dosage ; Myeloablative Agonists/adverse effects ; Myeloablative Agonists/pharmacokinetics ; Prognosis ; Retrospective Studies ; Risk Factors ; Transplantation, Homologous ; Vidarabine/administration & dosage ; Vidarabine/adverse effects ; Vidarabine/pharmacokinetics ; Vidarabine/therapeutic use ; Young Adult
مستخلص: Fludarabine is the most frequently used agent in conditioning regimens for allogeneic hematopoietic cell transplantation (HCT). Body surface area-based dosing leads to highly variable fludarabine exposure. We studied the relation between fludarabine exposure and clinical outcomes. A retrospective, pharmacokinetic-pharmacodynamic analysis was conducted with data from patients undergoing HCT with fludarabine (160 mg/m 2 ) as part of a myeloablative conditioning (busulfan targeted to an area under the plasma-concentration-time curve [AUC] of 90 mg*h/L) and rabbit antithymocyte globulin (6-10 mg/kg; from day -9/-12) between 2010 and 2016. Fludarabine exposure as AUC was calculated for each patient using a previously published population pharmacokinetic model and related to 2-year event-free survival (EFS) by means of (parametric) time-to-event models. Relapse, nonrelapse mortality (NRM), and graft failure were considered events. One hundred ninety-two patients were included (68 benign and 124 malignant disorders). The optimal fludarabine exposure was determined as an AUC of 20 mg*h/L. In the overexposed group, EFS was lower (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1-3.5; P = .02), due to higher NRM (HR, 3.4; 95% CI, 1.6-6.9; P < 001) associated with impaired immune reconstitution (HR, 0.43; 95% CI, 0.26-0.70; P < 001). The risks of NRM and graft failure were increased in the underexposed group (HR, 3.3; 95% CI, 1.2-9.4; P = .02; HR, 4.8; 95% CI, 1.2-19; P = .02, respectively). No relationship with relapse was found. Fludarabine exposure is a strong predictor of survival after HCT, stressing the importance of optimum fludarabine dosing. Individualized dosing, based on weight and "renal function" or "therapeutic drug monitoring," to achieve optimal fludarabine exposure might improve survival.
(© 2019 by The American Society of Hematology.)
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معلومات مُعتمدة: P30 CA008748 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Myeloablative Agonists)
FA2DM6879K (Vidarabine)
P2K93U8740 (fludarabine)
تواريخ الأحداث: Date Created: 20190721 Date Completed: 20200707 Latest Revision: 20200827
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6650734
DOI: 10.1182/bloodadvances.2018029421
PMID: 31324638
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2018029421