Evaluation of Oxidative Stress and Genotoxicity Inpatients Undergoing Autologous Hematopoietic Stemm Cell Transplantation

Fernando Duarte, Thayna Nogueira Santos, Romelia Pinheiro Gonçalves, Jacques Kaufman, Rosangela Ribeiro, Joao Paulo Leitao, Daniel Mazza, Beatriz Pitombeira
2014 Biology of Blood and Marrow Transplantation  
Objective: To compare the outcome of patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) conditioned with FluBuTBI or BEAM (BCNU, Etoposide, Cytarabine, and Melphalan) at our institution. Patients and Methods: We conducted a retrospective analysis of patients (n¼101) who underwent autologous PBSCT at our institution and were conditioned with BEAM (n¼63) or FluBuTBI (n¼38) between January 2006 and December 2012. Recipients were classified according to CIBMTR
more » ... g to CIBMTR criteria and those conditioned with BEAM were low risk (n¼17) and intermediate risk (n¼46). Recipients conditioned with FluBuTBI were low risk (n¼9), intermediate risk (n¼25), and high risk (n¼4). Median age of patients in the BEAM group was 52.3 years compared to 59.6 years for FluBuTBI. At the time of transplantation, 38 of 63 patients who received BEAM were in complete remission (60%) compared to 19 of 38 patients (50%) for FluBuTBI. Median time of follow up was 57 months for BEAM and 24 months for FluBuTBI. FluBuTBI consisted of intravenous (IV) Fludarabine 50 mg/ m 2 /day infused over 1 hour on days -6 through -2, IV Busulfan 3.2 mg/kg/day on days -5 through -2 (infusion rate 80 mg/kg/hour) and TBI 200 cGy on days -2 and -1. BEAM regimen consisted of IV BCNU 300 mg/m 2 infused over 1 hr on day -5, Etoposide 200 mg/m 2 /day over 3 hours on days -5 through -2, Cytarabine 200 mg/m 2 /day over 1 hour every 12 hours on days -5 through -2, and Melphalan 140 mg/m 2 over 1 hr on day -1. Diagnoses were Hodgkin's lymphoma (n¼26), B-cell lymphoma NOS (n¼3), anaplastic large cell lymphoma (n¼2), Burkitt's lymphoma (n¼3), diffuse large B-cell lymphoma (n¼ 23), follicular lymphoma (n¼16), mantle cell lymphoma (n¼22), peripheral T-cell lymphoma (n¼5), transformed follicular lymphoma (n¼1). Results: Overall survival at 3 years for patients undergoing BEAM was 71% and for FluBuTBI 72%. Cumulative incidence of disease progression or relapse at 3 years for BEAM was 39% compared to 32% for the FluBuTBI group. Treatment related mortality was 3% (n¼2) in the BEAM group and 0% in the FluBuTBI group. Treatment related MDS/AML occurred in 6% (n¼4) in the BEAM group compared to 2% (n¼1) in the Flu-BuTBI group. Grade 3-4 mucositis was seen in 16% (n¼6) in the FluBuTBI group compared to 4% (n¼3) in the BEAM group. Conclusion: Comparison of the two groups showed identical overall survival at 3 years, but a trend to reduced relapse, treatment related mortality and secondary MDS/AML, in patients conditioned with FluBuTBI. This difference was present despite older and higher risk patients in the FluBuTBI group. Mucositis was more frequent in the FluBuTBI group. Conditioning with FluBuTBI is a safe and effective alternative to BEAM for autologous PBSCT that offers the potential for further optimization by study of Busulfan pharmacokinetics and the introduction of targeted radiation. . The study consisted of control (n ¼ 30) consisted of healthy volunteers, adults, matched by sex and age with the patients group. Only one sample was collected from volunteers. Patients (n¼30) with oncohematologic diseases (multiple myeloma, non-Hodgkin lymphoma and Hodgkin lymphoma) that meet the basic conditions to the completion of the service accompanied HSCT Hematology HUWC. Determine the concentration of MDA (malondialdehyde), enzyme superoxide dismutase (SOD) and in the DI (damage index) were performed before the CR(conditioning regimen) (CR Pre), 24 hours after the CR (D -1), 1 day (D +1), 10 days (D +10 ) and 20 ( D +20 ) days after autologous HSCT. The determination of MDA based on its reaction with thiobarbituric acid (TBARS) in heparinized plasma and measuring the activity of superoxide dismutase (SOD) in erythrocytes were determined by spectrometry and comet assay, or technique of cell microgel electrophoresis was used to assess DNA damage. Statistical analysis was performed using GraphPad Prism. We used the ANOVA test for comparison of patients groups and controls. The level of significance is 5 % (p < .05). MDA levels in patients Undergoing HSCT between and control (p< .0001) and between D-1 and other groups (p < .0001). Levels of the antioxidant enzyme SOD in patients between control and pre CR (p ¼ .0048), control and D-1 (p < .0001), and between control and D +20 (p ¼ .0271), between Pre and D +1 CR (p < .0001) between D-1 and D +1 (p < .0001), D +10 and D+20 (p<.0001). An increase in ID in patient samples compared to controls. There was a significant increase in damage index 24 hours after the conditioning regimen (D-1) (56.63 AE 15.57) when compared to the control group (4.935 AE 2.038) and at other times examined. Results support the hypothesis stated HSCT induces an Increase in oxidative stress either by increased production of free radicals and by reduction of antioxidant enzymes with consequent damage of the DNA.
doi:10.1016/j.bbmt.2013.12.153 fatcat:dvlupjsffbfc7kniwkrlcljewi