Assessment the blood level of intravenous Busulfan and association with toxicity and survival following allogeneic hematopoietic cell transplantation in Iranian adults

Abstract

Introduction: Allogeneic hematopoietic stem cell transplantation is an effective treatment for various hematologic malignancies. Busulfan has been proposed as an alternative to pre-transplant radiation therapy and data indicate the efficacy of the BU-based diet in patients with leukemia. However, failure to adjust the BU dose in patients can lead to venous occlusion and other complications. Objective: To determine the appropriate method for determining the amount of busulfan in the blood sample of patients and to establish a relationship between the level of busulfan with the occurrence of side effects and mortality in Iranian adults under bone marrow allogeneic transplantation. Materials and Methods: Thirteen patients who were to undergo allogeneic bone marrow transplantation were included in our study. Intravenous busulfan at a dose of 0.8 mg per kg of body weight was prescribed to patients as an allogeneic transplant conditioning regimen. Blood samples were taken at specified hours after the end of the infusion and immediately transferred to the laboratory to measure the AUC of busulfan by HPLC. Results: The results of this study showed that the higher the AUC of busulfan in patients, the lower the risk of cutaneous GVHD, the higher the risk of hepatic GVHD and the lower the risk of gastrointestinal GVHD. On the other hand, the higher the AUC of busulfan in patients, the lower the risk of sinus obstruction syndrome. Also, no correlation was observed between busulfan AUC and recurrence rate and mortality in patients. Conclusion: Almost all patients after the first dose of the drug were out of the AUC range, which indicates the potential benefits of monitoring the drug concentration and the appropriate dose. Repeated doses result in an AUC above the desired range, so it is important to determine the appropriate time and dose for re-injection.