4. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995; 333:1540-1545. 5. William BM, Loberiza FR Jr, Whalen V, et al. Impact of conditioning regimen on outcome of 2-year disease-free survivors of autologous stem cell transplantation for Hodgkin lymphoma. Clin Lymph Myel Leuk. 2013;13:417-423. 6. Xie H, Griskevicius L, Stahle L, et al. Pharmacogenetics of cyclophos- phamide in patients with hematological malignancies. Eur J Pharm Sci. 2006;27:54-61. 7. Takada K, Arefayene M, Desta Z, et al. Cytochrome P450 pharmacoge- netics as a predictor of toxicity and clinical response to pulse cyclo- phosphamide in lupus nephritis. Arthritis Rheum. 2004;50:2202-2210. 8. Raccor BS, Claessens AJ, Dinh JC, et al. Potential contribution of cyto- chrome P450 2B6 to hepatic 4-hydroxycyclophosphamide formation in vitro and in vivo. Drug Metab Dispos. 2012;40:54-63. 9. Thorn CF, Lamba JK, Lamba V, et al. PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenet Genom. 2010;20:520-523. 10. Cheson BD. New staging and response criteria for non-Hodgkin lym- phoma and Hodgkin lymphoma. Radiol Clin North Am. 2008;46: 213-223. vii. 11. Kaplan EL, Meier P. Nonparametric estimation from incomplete ob- servations. J Am Stat Assoc. 1958;53:457-481. 12. Lin DY. Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med. 1997;16:901-910. 13. Cox DR. Regression models and life tables. J R Stat Soc B. 1972;34: 187-220. 14. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat. 1979;6:65-70. 15. Helsby NA, Hui CY, Goldthorpe MA, et al. The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bio- activation. Br J Clin Pharmacol. 2010;70:844-853. 16. Rocha V, Porcher R, Fernandes JF, et al. Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell trans- plantation for patients with leukemia. Leukemia. 2009;23:545-556. 17. Black JL, Litzow MR, Hogan WJ, et al. Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients. Leuk Res. 2012;36:59-66. 18. Melanson SE, Stevenson K, Kim H, et al. Allelic variations in CYP2B6 and CYP2C19 and survival of patients receiving cyclophosphamide prior to myeloablative hematopoietic stem cell transplantation. Am J Hematol. 2010;85:967-971. 19. Zanger UM, Klein K. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Front Genet. 2013;4:24. 20. Ekhart C, Doodeman VD, Rodenhuis S, et al. Influence of poly- morphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydrox- ycyclophosphamide. Pharmacogenet Genom. 2008;18:515-523. 21. Helsby NA, Tingle MD. Which CYP2B6 variants have functional con- sequences for cyclophosphamide bioactivation? Drug Metab Dispos. 2012;40:635-637. 22. Salar A, Sierra J, Gandarillas M, et al. Autologous stem cell trans- plantation for clinically aggressive non-Hodgkin’s lymphoma: the role of preparative regimens. Bone Marrow Transplant. 2001;27:405-412. 23. Johnson GG, Lin K, Cox TF, et al. CYP2B6*6 is an independent deter- minant of inferior response to fludarabine plus cyclophosphamide in chronic lymphocytic leukemia. Blood. 2013;122:4253-4258. Association between Plasma Endothelin-1, Transforming Growth Factor-b, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation S ¸ ahika Zeynep Akı 1 , Elif Suyanı 1 , Mustafa Cengiz 2, * , Seren Özenirler 3 ,S ¸ ehri Elbe  g 4 , Hatice Pas ¸ ao  glu 4 , Gülsan Türköz Sucak 1 1 Faculty of Medicine, Department of Haematology, Gazi University, Ankara, Turkey 2 Department of Gastroenterology, Dr. A.Y. Ankara Oncology Training and Research Hospital, Ankara, Turkey 3 Department of Gastroenterology, Gazi University, Ankara, Turkey 4 Department of Biochemistry, Gazi University, Ankara, Turkey Article history: Received 16 November 2014 Accepted 3 February 2015 Key Words: Hematopoietic stem cell transplantation Liver injury Endothelin-1 Transforming growth factor-b Fibroblast growth factor Nitric oxide Iron overload Graft-versus-host disease abstract Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-b (TGF-b), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-b, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range,13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-b, and FGF were 81.54  21.62 mmol/mL, 31.82  26.42 mmol/mL, 2.56  0.77 ng/mL, and 50.31  32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean Financial disclosure: See Acknowledgments on page 952. * Correspondence and reprint requests: Mustafa Cengiz, MD, Ankara Oncology Education and Research Hospital, Department of Gastroenter- ology, Mehmet Akif Ersoy Mahallesi, 13. Cadde No. 56, Demetevler, Yeni- mahalle, Ankara, Turkey. E-mail address: drmustafacen@gmail.com (M. Cengiz). 1083-8791/Ó 2015 American Society for Blood and Marrow Transplantation. http://dx.doi.org/10.1016/j.bbmt.2015.02.002 S ¸ .Z. Akı et al. / Biol Blood Marrow Transplant 21 (2015) 934e953 948