ALBERT

Description: Background and Objectives: Bacterial sepsis is a common complication in pediatric patients with acute myeloid leukemia (AML) undergoing intensive myelosuppressive chemotherapy. Up to 60% of children experience at least one documented infectious complication during therapy, with bacterial causes being most common; infection related mortality may reach 11% (Sung et al, Pediatric Blood & Cancer, 2008). Randomized controlled trials in children undergoing intensive chemotherapy have demonstrated a reduction in bacteremia risk with prophylactic levofloxacin use. This study evaluates epidemiologic data regarding factors associated with levofloxacin use, the impact of levofloxacin on infectious outcomes and the cost-effectiveness of this strategy. Methods: We queried the Pediatric Health Information System (PHIS) database, which collects billing and coding data from 52 pediatric hospitals, for inpatient encounters of children with AML admitted for chemotherapy with a length of stay ≥14 days from 2013-2018. We collected demographics, information on infectious outcomes and utilization of hospital resources. Variables were compared between children who received levofloxacin prophylaxis during their hospitalization and those who did not using chi-square or Fisher's exact test for categorical variables and t-test of means for continuous variables. We next developed a decision model comparing levofloxacin prophylaxis through count nadir until recovery to no prophylaxis during a single chemotherapy cycle for AML using published data from randomized controlled trials. We assumed bacteremia was present only in the setting of fevers. We used published literature to estimate the probability of ICU admission or death with or without bacteremia. It was assumed that antibacterial prophylaxis only altered the probabilities of febrile neutropenia and bacteremia. Strategies were compared to analyze incremental costs per bacteremia episode avoided, ICU admission avoided and death avoided. Medication costs were obtained from the Federal Supply Schedule. Costs related to infectious complications and ICU admissions were obtained for patients with AML from PHIS during the 2018 calendar year. Multiple sensitivity analyses tested the robustness of results. Results: Overall, 26.3% of children received levofloxacin prophylaxis. The decision to use prophylaxis varied significantly by geographic division, AML disease status, year of admission and chemotherapy regimen (Table 1). Patients who received prophylaxis had decreased risk of bacterial infection, C. diff infection, ICU admission and overall antibiotic exposure, not including levofloxacin, during that encounter (Table 2). There was no significant difference between groups regarding length of stay or hospitalization costs. In PHIS, each bacteremia episode added an average of $119,478 to hospitalization costs. Using baseline probabilities from our literature review, levofloxacin prophylaxis cost $7,252 per bacteremia episode avoided compared with no prophylaxis. This resulted in cost savings of over $100,000 with prophylaxis as the favored strategy. When probabilities for each parameter in the model were altered by 1-way sensitivity analyses, results were sensitive to variation in bacteremia risk with prophylaxis, febrile neutropenia risk, levofloxacin cost and the cost of levofloxacin-related adverse events. However, none of the variations in parameter values generated a result which exceeded a cost-effectiveness threshold of $50,000 per bacteremia episode avoided. In a probabilistic sensitivity analysis, when all parameters were varied simultaneously over the distribution of their potential probabilities, the probability that levofloxacin use was cost-effective at a willingness-to-pay threshold of $50,000 was 95.1%. When considering other outcomes, levofloxacin prophylaxis cost $73,088 per ICU admission avoided compared to actual added costs of $94,181, or $198,525 per death avoided. Conclusions: Based on available evidence, antibacterial prophylaxis with levofloxacin is effective in reducing bacterial sepsis in pediatric AML patients undergoing intensive chemotherapy. Levofloxacin prophylaxis may also be cost saving when the costs of infectious complications and other adverse health outcomes are considered.

Description: Introduction Improvements in multi-modal therapies have increased survival rates for older adults diagnosed with B-cell Non-Hodgkin Lymphoma (B-NHL). Despite this success, B-NHL survivors are at an increased risk for developing long-term and late complications of these therapies thereby compromising survival. Several studies have reported an increased risk in diabetes mellitus (DM) among long-term survivors of Hodgkin lymphoma and pediatric cancers. However, there are limited data on the risk of DM and its risk factors in older adults following treatment for B-NHL. Using data from the Utah Population Database, we evaluated the association between treatment for B-NHL and DM risk and furthermore compared this risk to a matched Utah general population. We hypothesized that the risk of DM among B-NHL survivors would be significantly increased compared to the general population. Methods Adult (age 〉18 years at diagnosis) survivors of primary B-NHL living in Utah at the time of diagnosis between 1997-2013, without a previous diagnosis of DM, and matched (1:4) to individuals without a prior history of DM from the Utah general population for birth year, birth state, and sex were included. New DM diagnoses were identified for all-time, 0-1, 1-5, and 5-10 years following a diagnosis of B-NHL. Adjusting for sex, race, baseline body mass index (BMI), and Charlson Comorbidity Index (CCI) scores, multivariate Cox proportional hazard analysis was performed to estimate the adjusted hazard ratio (aHR) of DM in B-NHL survivors compared with that in matched non-B-NHL individuals. Risk factors for DM were evaluated, including age at diagnosis, race, sex, BMI at baseline, family history of DM, cancer stage at diagnosis, and treatment modality. The risk of developing DM during all-time, 0 to 1, 1 to 5, and 5 to 10 years follow-up after adjusting for demographic variables was analyzed by age (〈 40, 40-65, and 〉65 years) at diagnosis of B-NHL. Results The study population included 3,970 B-NHL survivors and 19,821 matched individuals from the general population. At the time of diagnosis, the majority of B-NHL patients were age 60 or greater (61.4%), had diffuse large B-cell lymphoma (46%) or follicular lymphoma (26.4%), distant cancer stage (50.1%), and received chemotherapy (27.5%). DM was diagnosed in 897 (22.6%) B-NHL survivors and 3,253 (16.4%) non-B-NHL adults. The majority in both groups were male (B-NHL: 55.5%; controls: 55.5%), white (B-NHL: 97.4%; controls: 93.8%), overweight [BMI 25-29.9 kg/m2 (B-NHL: 40.7%; controls: 40.6%)] or obese [BMI ≥30 kg/m2 (B-NHL: 21.8%; controls: 18.5%)]. The risk of developing DM among B-NHL survivors compared to the control group was significantly increased over all time (HR, 1.34; 95% CI 1.24 - 1.44) and the 0 to 1 year follow-up period (HR, 1.28; 95% CI 1.15 - 1.43)(Table 1). Multivariable analysis for DM risk showed that age 40-65 years and BMI ≥25 were factors independently associated with developing DM at all-time, 0 to 1, 1 to 5, and 5 to 10 years after diagnosis of B-NHL. Male sex and a family history of DM were significantly associated with development of DM during all time, 1 to 5, and 5 to 10 year follow-up periods. Distant cancer stage at diagnosis was a significant risk factor for DM at all time and 1 to 5 years while receipt of chemotherapy only or chemotherapy with radiation were significantly associated with development of DM at 5 to 10 years after diagnosis of B-NHL (estimated aHR and CIs are shown in Table 2). There was no significant association between race and the development of DM. Conclusion Adult survivors of B-NHL have an overall significantly higher risk of developing DM in the first year and over all time following a diagnosis of B-NHL compared to the general population. Age 40 to 65 years and BMI ≥25 were significant risk factors for DM across all follow-up periods while treatment with chemotherapy only or chemotherapy with radiation significantly increased the risk of DM 5-10 years after diagnosis of B-NHL. Race did not appear to be a risk factor for DM but this result may reflect the homogeneity of our study population. These findings contribute important information to the existing literature regarding the risk of developing DM in adult B-NHL survivors and provide foundation for the development of screening and management guidelines for DM in the B-NHL survivor population. Disclosures No relevant conflicts of interest to declare.

Description: Background: Asparaginase is a critical therapy component for childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions and silent inactivation by neutralizing antibodies can lead to withholding further doses. Reactions occur in 10-20% of children receiving the commonly used, widely available pegylated asparaginase. The less immunogenic Erwinia asparaginase may allow continued administration, but requires more frequent dosing and is subject to limitations in availability. Inability to receive all recommended asparaginase doses decreases disease-free survival. Premedication with antihistamines, antipyretics and steroids decreases hypersensitivity reaction frequency, preventing the need for alternates. The cost-effectiveness of premedication strategies in childhood ALL is unclear. Methods: We used a Markov model to estimate strategy costs and quality-adjusted life years (QALYs) for two patient scenarios: a 3-year-old with standard-risk ALL receiving 2 asparaginase doses, and a 15-year-old with high-risk ALL receiving 7 asparaginase doses over a 5-year time horizon. Patients entering the model received premedication with serum asparaginase level monitoring, monitoring only, or no premedication/monitoring. Literature data were used for hypersensitivity reaction and silent inactivation risks following each asparaginase dose. Silent inactivation was not identified the non-monitoring strategy. Disease outcomes, therapy and associated additional care costs, and health state quality-of-life utilities were obtained from the literature and US databases. Evaluation took the societal perspective, with costs and effectiveness discounted at 3%/yr. Multiple sensitivity analyses were performed. Results: In both the standard-risk and high-risk analyses, premedication was the least costly strategy. In the standard-risk model, premedication with monitoring cost $4,586 less than monitoring alone, resulted in 8% fewer changes to Erwinia and 0.01 additional QALYs. It cost $1,993 less than no premedication/monitoring, resulted in 3% fewer changes and 0.08 additional QALYs. In the high-risk model, premedication cost $29,757 less than monitoring alone, resulted in 7% fewer medication changes and 0.01 fewer QALYS; thus, monitoring alone was expensive, costing 〉$2 million/QALY gained compared to premedication and monitoring. Premedication cost $11,255 less than no premedication/monitoring, resulted in 2% fewer changes and 0.07 additional QALYs. Individual variation of all model inputs did not change the favorability of premedication and monitoring for either model. In probabilistic sensitivity analyses varying all parameters simultaneously over distributions 1000 times, premedication and monitoring was favored in 〉86% of model iterations in both standard- and high-risk scenarios. Conclusion: Compared to other strategies, premedication use and asparaginase level monitoring in children with ALL is economically reasonable and potentially cost-saving. Disclosures No relevant conflicts of interest to declare.