Abstract B129: Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly non-Hodgkin's lymphoma patients

Abstract

Abstract Therapy-related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML), defined as MDS or AML occurring after myelosuppressive chemotherapy and/or radiation therapy, are devastating long-term complications of cancer therapy. White blood cell growth factors (CSFs) are supportive care agents intended to minimize risk of febrile neutropenia in patients receiving chemotherapy. However, evidence suggests that CSFs may increase risk of t-MDS/AML, possibly due to the observation that CSFs not only stimulate the proliferation and differentiation of hematopoietic stem cells, but also interfere with apoptosis. The purpose of this study was to evaluate the association between CSF use and t-MDS/AML among a large population-based cohort of elderly non-Hodgkin's lymphoma (NHL) patients treated with chemotherapy. We identified 13,203 NHL patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed from 1992 to 2002 who received chemotherapy within 12 months of diagnosis. Patients were followed from their initial chemotherapy date until t-MDS/AML development, death, or end of study period (October 31, 2006). Overall, 40% (n=5,266) of patients received CSF. A total of 272 (5.2%) of patients receiving CSF developed t-MDS/AML vs. 230 (2.9%) who did not receive CSF: there was a statistically significant higher incidence of t-MDS/AML among patients receiving CSF compared to patients not receiving CSF (log-rank p<0.0001). In a multivariable Cox regression analysis adjusting for gender, histology, stage, comorbidities, chemotherapy dates, and chemotherapy agent, CSF use was independently associated with a 53% increased risk of t-MDS/AML (HR 1.53; 95% CI 1.26 – 1.84). A dose-response relationship was observed, with t-MDS/AML risk increasing by quartile of CSF claims. In an evaluation of plausible biologic interactions, we found that patients who received both CSF and antimetabolite chemotherapy had a 2.5 fold increased risk of t-MDS/AML (HR 2.49; 95% CI 1.91 – 3.26) vs. patients who received neither agent (p-interaction=0.04). This observation has added clinical significance considering that approximately 10% of the overall population received this therapeutic combination. To our knowledge, this is the first large population-based study to evaluate the association between CSF use and t-MDS/AML risk among NHL patients. Findings support our hypothesis that the administration of CSF among elderly NHL patients receiving chemotherapy may increase the risk of t-MDS/AML, even though the absolute risk is low in these populations. Future studies are necessary to verify these results and to determine the potential clinical implications of the observed interaction between CSF use and antimetabolite chemotherapy. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B129.