Treatment of Hodgkin Lymphoma without G-CSF Does Not Increase the Risk of Febrile Neutropenia.

Patients with Hodgkin Lymphoma (HL) being treated with ABVD chemotherapy frequently develop neutropenia, though the complication of febrile neutropenia is relatively uncommon. In most cancer centres, including our own until recently, the presence of neutropenia on the planned day of chemotherapy administration (absolute neutrophil count (ANC) <1.5×10⁹/L) often resulted in delays in chemotherapy administration and/or dose attenuation, plus the addition of G-CSF prophylaxis through all subsequent cycles of chemotherapy. G-CSF is costly and it can cause side effects such as bone pain. There is also some suggestion in the literature that G-CSF may increase the risk of bleomycin lung toxicity (BLT). Several retrospective studies have reported that full dose ABVD can be safely administered to patients without routine G-CSF support, regardless of the neutrophil count on the day of treatment. Based on this data, our centre decided to change the practice of routinely delaying chemotherapy and starting G-CSF prophylaxis in neutropenic patients, and to prospectively monitor the safety of this practice change. We present the results of our planned interim safety analysis.

Newly diagnosed patients with HL with no bone marrow involvement and no significant co-morbidities were enrolled and followed prospectively throughout their treatment. ABVD chemotherapy was administered every two weeks without dose delay or attenuation and without the addition of G-CSF, regardless of the neutrophil count on the day of treatment. Dose reductions were permitted for non-hematological toxicities. G-CSF was added as secondary prophylaxis to all subsequent cycles in patients who developed febrile neutropenia. We also retrospectively reviewed the charts of patients with HL treated with ABVD at our centre from 2004-2007 (prior to practice change) and collected data on the incidence of neutropenia, febrile neutropenia, G-CSF use and BLT. Continuous variables were analysed using the Mann Whitney U test and dichotomous variables using Chi squared analysis.

Since September 2008, 17 patients have been enrolled in the study. No patients met criteria for exclusion. A total of 149 ‘doses' (half cycles) of ABVD have been administered so far. Table 1 shows demographic information on the prospective and retrospective patient populations, as well as rates of neutropenia, febrile neutropenia, and BLT. Almost all study patients (15/17, 88%) had documented neutropenia at some point during treatment, the majority (13 patients) as early as cycle 1B. Excluding cycle 1A, the median neutrophil count on day of treatment was 1.3×10⁹/L. Half of the chemotherapy doses (74/149) were administered with an ANC <1.5×10⁹/L; one third (52 doses) with grade 3/4 neutropenia. None of the chemotherapy was dose reduced (except for non-hematologic toxicity) and most of the treatments were given on time, with a median dose interval of 14 days. One patient developed BLT after cycle 4B. There was 1 episode of low risk febrile neutropenia occurring after cycle 3B in which no causative organism was identified. This patient received all subsequent chemotherapy with G-CSF prophylaxis with no further episodes of neutropenic fever.

This interim analysis shows that ABVD chemotherapy can be safely administered to patients with HL without dose attenuation, delays or the routine use of G-CSF prophylaxis in the setting of neutropenia. This practice change resulted in a similar very low rate of febrile neutropenia (<1%), but significant reductions in cost and dose delay secondary to neutropenia.

No relevant conflicts of interest to declare.