G-CSF as Secondary Prophylaxis of Febrile Neutropenia In the Management of Advanced-Stage Hodgkin Lymphoma Treated with ABVD Chemotherapy: A Decision Analysis.

ABVD is the standard treatment for advanced stage Hodgkin Lymphoma (HL) with rates of complete remission achieved in the majority of patients treated. Current practice guidelines (American Society of Clinical Oncology, Smith TJ et al. JCO 2008) recommend the use of granulocyte colony stimulating factor (G-CSF) in secondary prophylaxis despite lack of a survival benefit and potential toxicities, including bleomycin pulmonary toxicity (BPT). Recently, small retrospective series and expert opinion (Horning S, ASH Education Program Book 2007) advocate for the omission of G-CSF, although this approach has not been prospectively studied. The purpose of this study was to perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of advanced-stage HL managed with and without secondary prophylactic G-CSF.

We constructed a decision-analytic model to compare the strategy of secondary prophylaxis with G-CSF to a strategy of no G-CSF with severe neutropenia for a hypothetical cohort of 40 year-old patients with clinical stage IIB to IV Hodgkin Lymphoma treated with 8 cycles of ABVD chemotherapy. Markov models were used to simulate a 2-year clinical course of patients. Baseline probability estimates were derived from a systematic review of relevant published studies. Utilities for various health states were derived from expert opinion. One-way sensitivity analysis was performed on key variables such as severe neutropenia, febrile neutropenia and bleomycin pulmonary toxicity, as well as the utilites associated with these health states.

The life expectancy was 1.858 years for the G-CSF strategy and 1.875 years for no G-CSF, yielding a net expected benefit of 0.017 years for no G-CSF use in severe neutropenia. The quality-adjusted life expectancy was 1.371 years for the G-CSF strategy and 1.408 years for no G-CSF with a net expected benefit for no G-CSF of 0.037 QALYs. On microsimulation (10,000 trials), 96% of the simulations showed that the no G-CSF strategy is preferred to the use of G-CSF. This analysis was not sensitive to the odds ratio of lung toxicity with G-CSF, the hazard ratios of febrile neutropenia and severe neutropenia, the probability of death from febrile neutropenia, or the utilities associated with bleomycin pulmonary toxicity, hospitalization for febrile neutropenia and musculoskeletal pain from G-CSF.

While the difference between the two strategies is small, our model predicted that for a 40 year-old patient with advanced-stage Hodgkin Lymphoma treated with ABVD chemotherapy, the strategy of avoiding use of G-CSF with severe neutropenia is preferred. This finding is robust across a wide range of sensitivity analyses.

No relevant conflicts of interest to declare.