Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

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.

Medication Desensitization: Single Intravenous Bag Method, in 3 Pediatric Patients.

Chemotherapies and biologic agents are known to cause hypersensitivity reactions (HSRs). It is imperative that pediatric patients receive these agents to treat their cancer or other rare condition, as oftentimes there are no available therapeutic alternatives. Successful medication desensitization has been described previously with a 12-step method using 3 intravenous (IV) infusion bags of varying concentrations. However, this 12-step process is time and resource intensive and increases the risk for medication errors. A recent study successfully used a simplified 12-step method with a single IV infusion bag for a paclitaxel desensitization. From the results of this study, our institution used this single IV infusion bag method for desensitization with 3 different medications. Two of these experiences were successful. We share those 3 experiences in this report.

Characterization of Febrile Neutropenia Management in Children With Malignancies: A Single-Center Evaluation.

OBJECTIVE: Current recommendations for febrile neutropenia (FN) include initiation of broad-spectrum antibiotics without clear indications of when or how to de-escalate or target therapy, especially in those without microbiologically defined bloodstream infections (MD-BSIs). The purpose of this study is to characterize a pediatric FN population, FN management, and identify the proportion of patients with MD-BSI. METHODS: This study was a single-center, retrospective chart review of patients admitted to the University of North Carolina Children's Hospital between January 1, 2016, and December 31, 2019, with a diagnosis of FN. RESULTS: There were 81 unique encounters included in this study. MD-BSI was the etiology of fever in 8 FN episodes (9.9%). The most common empiric antibiotic regimen was cefepime (62%) followed by cefepime and vancomycin (25%). The most common de-escalation type was the discontinuation of vancomycin (83.3%), and the most common type of escalation was the addition of vancomycin (50%). The median antibiotic total duration in patients without MDI-BSI was 3 days (IQR, 5-9). CONCLUSIONS: In this single-center, retrospective review, most FN episodes were not due to an MD-BSI. There were inconsistencies in practice of when discontinuation of antibiotic therapy occurred in patients without MD-BSI. De-escalation or cessation of antibiotic therapy before neutropenia resolution did not result in any documented complication. These data suggest a role for implementing an institutional guideline to improve consistency in antimicrobial use in pediatric patients with febrile neutropenia.

Impact of Adherence to Ibrutinib on Clinical Outcomes in Real-World Patients With Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with clonal expansion of small lymphocytes. Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a first-line treatment option, and recent data suggest that strict adherence is directly related to clinical outcomes. OBJECTIVES: The primary objective of this study was to quantify ibrutinib adherence rates in real-world patients with CLL on ibrutinib; secondary outcomes included progression-free survival and overall survival. METHODS: This retrospective study included subjects who were treated at a large academic medical center over approximately 5 years. Subjects were at least 18 years, diagnosed with CLL or small lymphocytic lymphoma, and treated with ibrutinib monotherapy for at least 6 months. Adherence was quantified using the medication possession ratio (MPR), which is the ratio of the sum of days' supply of medication in a period over the number of days in that period, and was based on fill history from the medical center's specialty pharmacy. RESULTS: For the 32 subjects in this study, the mean ibrutinib adherence rate was 91.7% (range, 84.4%-100%). Only 3 subjects had disease progression, and 1 death was recorded while on therapy (all with MPR < 95%); therefore, analyses of clinical outcomes were unable to be assessed due to a low number of events. There were no statistically significant differences in rates of adherence based on baseline characteristics and adverse drug events. CONCLUSION: In patients with CLL treated with ibrutinib, mean adherence was 91.7%, which is lower than rates seen in clinical trials.

Novel therapies for treatment of resistant and refractory nontuberculous mycobacterial infections in patients with cystic fibrosis.

Respiratory infections caused by non-tuberculous mycobacteria (NTM) are a major cause of morbidity for patients living with cystic fibrosis (CF), as NTM pulmonary disease (NTM-PD) is challenging to both diagnose and eradicate. Despite the lengthy courses of the established regimens recommended by the Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) consensus guidelines, only about 50% to 60% of patients achieve culture conversion, and treatment regimens are often complicated by antibiotic resistance and toxicities. Since publication of the CFF/ECFS guidelines, several new or alternative antibiotic regimens have been described for patients with CF who have NTM-PD. These regimens offer new options for patients who do not clear NTM with standard therapies or cannot utilize the usual regimens due to toxicities or drug-drug interactions.