ABSTRACT
BACKGROUND: 6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/µL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. PROCEDURE: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.
ABSTRACT
INTRODUCTION: The increasing incidence of cancer and capacity for cancer care in Ethiopia has led to an upsurge in chemotherapy use in the country; however, studies indicate that there is a gap in the safe handling of chemotherapy by healthcare workers. There exists a need to understand if such unsafe practices occur in Ethiopia and, if so, which areas along the chemotherapy life cycle need the most improvement. METHODS: This study utilized a multi-method design through an online survey administered to health care professionals and evaluative site visits of eight cancer units in Addis Ababa, Ethiopia to understand the current conditions of chemotherapy handling. In addition, a survey was conducted among Ethiopian health care professionals from across the country. RESULTS: Fifty-five percent of survey participants disagreed or strongly disagreed that there are systems in place to identify, prevent, and address chemotherapy hazards in their workplace, and 71% of respondents denied having an active and effective health and safety committee and/or worker health and safety representative where they work. At evaluative site visits, only 30% of health care workers met the minimum guidelines for proper hand hygiene, and 20% of health care workers used adequate Personal Protective Equipment according to guidelines across the chemotherapy lifecycle. CONCLUSIONS: Results of this study indicate an urgent need for implementation of evidence-based interventions to improve chemotherapy handling in Ethiopia so that all patients and health care workers are protected from the hazardous toxicities of these drugs.
