Minuk, L.A., Monkman, K., Chin-Yee, I.H., Lazo-Langner, A., Bhagirath, V., Chin-Yee, B.H., & Mangel, J.E. (2012). Treatment of Hodgkin lymphoma with adriamycin, bleomycin, vinblastine and dacarbazine without routine granulocyte-colony stimulating factor support does not increase the risk of febrile neutropenia: A prospective cohort study. Leukemia and Lymphoma, 53, 57–63.

The purpose of the study was to evaluate a protocol change of not routinely prescribing G-CSF to manage uncomplicated neutropenia in patients with Hodgkin lymphoma on adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.

Eligible patients who consented to participate had baseline data collected (demographics, comorbidities, standard blood tests, routing staging via computed tomography scan, and bone marrow biopsies when indicated, and prognostic factors). Response rates were evaluated via repeat computed tomography scans following completion of ABVD therapy. Patients with limited stage disease received 2–4 cycles of ABVD with involved field radiation and those with advanced stage disease received 6–8 cycles of ABVD. Blood tests were taken every two weeks. No primary prophylactic G-CSF was administered; but was given as secondary prophylactic for febrile neutropenia. Adjustments were made to the chemotherapy regimen for nonhematologic toxicities (peripheral neuropathy or lung toxicity). Comparisons were made to a retrospective chart review in which C-GSF was administered as primary prophylaxis.

• 33 in the prospective group, 89 in the retrospective study group
• Mean age was 38 years in the prospective group and 42 years in the retrospective group.
• 18 males (55%) were in the prospective group and 50 (56%) were in the retrospective group. 15 females (45%) were in the prospective group and 39 (46%) were in the retrospective group
• Key disease characteristics include biopsy-proven Hodgkin lymphoma
• Participants were excluded if neutropenic or if they had significant cytopenias prior to starting chemotherapy, Hodgkin lymphoma-related bone marrow involvement, initiating chemotherapy as an inpatient, and/or comorbidities of HIV, active infection, or severe cardiac or pulmonary disease

A single-site outpatient location (the London Regional Cancer Program)

Active antitumor treatment

Prospective cohort with comparison to historical cohort

• Statistical analyses included using two-tailed Mann-Whitney U test for continuous variable comparisons with chi-square or Fisher’s exact test for proportional comparisons.
• Taylor series approximation was used to calculate the absolute difference in risk of developing febrile neutropenia.
• Cost analysis was also conducted.

Six percent of patients in the prospective group (did not receive primary prophylactic G-CSF) acquired febrile neutropenia, interfering with 0.6% of chemotherapy treatments. There was no significant difference from the retrospective comparison group in rate of febrile neutropenia, although the prospective group had a significantly higher rate of neutropenia (p < 0.001). The cost savings to the institution of not using primary prophylactic G-CSF was $10,241.

Not using G-CSF as a primary prophylactic treatment for patients with uncomplicated neutropenia who are being treated with ABVD for Hodgkin lymphoma is safe and cost saving.

• Small sample (less than 100 participants)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Closely monitoring patients for febrile neutropenia would be highly important in patients not receiving G-CSF as primary prophylaxis. Educating patients and healthcare providers about the safety of not using G-CSF as a primary prophylactic treatment is important. While this study provides some evidence that primary prophylaxis may not be of benefit related to development of febrile neutropenia, the ability to draw firm conclusions is limited by study design and other limitations. Ongoing research in the most cost effective way to prevent infection is needed.