Clinical outcomes and cost-effectiveness of white blood cell growth factors in elderly patients with non -Hodgkin's lymphoma: Findings from a large population-based cohort
This project was divided into three papers with the following aims: (1) Explore the relationship between CSF use and the development of therapy-related acute myeloid leukemia or myelodysplastic syndromes (t-MDS/AML); (2) Evaluate the population-based effectiveness of CSF use. Outcomes included incidence of febrile neutropenia/infection and overall survival; and (3) Evaluate the cost-effectiveness of CSF use from a payer's perspective. The study utilized data from the SEER-Medicare database, a large repository of population-based registry data linked to Medicare claims data. We identified 13,203 NHL patients from the database who received chemotherapy within 12 months of diagnosis. Primary prophylaxis was defined as CSF administered at the start of chemotherapy prior to the incidence of febrile neutropenia/infection, while secondary prophylaxis was defined as CSF use after a febrile neutropenia/infection event. Patients were followed from their initial chemotherapy date until t-MDS/AML development, death, or end of study period (October 31, 2006) for the purposes of addressing each study aim. In the first paper, we found that CSF use was independently associated with a 53% increased risk of t-MDS/AML (HR 1.53; 95% CI 1.26 – 1.84) after adjusting for gender, histology, stage, comorbidities, chemotherapy dates, and chemotherapy agent. A dose-response was observed, with t-MDS/AML risk increasing by quartile of CSF claims. The observed association between CSF use and t-MDS/AML persisted across histologic subgroups (i.e. diffuse large B cell lymphoma, follicular lymphoma, other). In an evaluation of plausible interactions between CSF use and specific chemotherapy agents, we found a significant interaction (p=0.04) between CSF use and the use of antimetabolite chemotherapy. Patients who received both agents had a 2.5 fold increased risk of t-MDS/AML (HR 2.49; 95% CI 1.91 - 3.26) compared to patients with who received neither agent. In the second paper evaluating clinical outcomes (incidence of febrile neutropenia/infection and overall survival), we found that patients with 5-9 claims for primary prophylactic CSF use had a 42% reduced risk of febrile neutropenia (OR 0.58; 95% CI 0.41 – 0.83), and patients with 10+ claims had a 48% reduced risk of febrile neutropenia (OR 0.52; 95% CI 0.36 – 0.76) after adjusting for age, marital status, stage, histology, comorbidity score, chemotherapy agent, and number of chemotherapy claims. A similar protective association was observed between primary prophylactic CSF use and incidence of infection. After adjusting for relevant clinical and demographic covariates, we found that patients with 5-9 CSF claims had a 27% reduced incidence of infection (OR 0.73; 95% CI 0.55 – 0.96) while patient with 10+ claims had a 52% reduced risk (OR 0.48; 95% CI 0.35 – 0.66). Results did not differ significant when we adjusted for propensity score or when we used a more liberal definition of febrile neutropenia. In the evaluation of overall survival, we did not find an association between primary prophylactic CSF use and overall survival. However, we found that secondary prophylactic CSF use was associated with improved overall survival. After adjusting for relevant covariates, 4-10 administrations of secondary prophylactic CSF was associated with a 9% reduction is risk of mortality (HR 0.91; 95% CI 0.84 – 0.99), 11-23 administrations was associated with a 23% reduction (HR 0.77; 95% CI 0.71 – 0.84) and greater than 23 administrations was associated with a 13% reduction in risk of mortality (HR 0.87; 95% CI 0.79 – 0.95) compared to patients who did not receive any CSF following neutropenia, fever, and/or infection. Results from our cost-effectiveness analysis (3rd paper) suggest that primary prophylactic CSF use was cost-effective at lower willingness to pay thresholds, whereas at higher thresholds, not providing prophylactic CSF became the cost-effective strategy. For secondary prophylactic CSF use among patients experiencing neutropenia, fever, and/or infection, the opposite trend was observed. For low willingness to pay thresholds (less than $20,000 per life year gained), not administering CSF was the cost-effective strategy, while CSF use became cost-effective as willingness to pay increased (from $100,000+ per life year gained). (Abstract shortened by UMI.)
Gruschkus, Stephen K, "Clinical outcomes and cost-effectiveness of white blood cell growth factors in elderly patients with non -Hodgkin's lymphoma: Findings from a large population-based cohort" (2009). Texas Medical Center Dissertations (via ProQuest). AAI3366233.