Evidence-based review and meta-analysis of the use of hematopoietic growth factors (hgf) in the management of malignant lymphoma (ml)

The use of HGFs to prevent febrile neutropenia (FN) and maintain dose and schedule adherence in patients (pts) receiving combination chemotherapy for ML is widespread. Several trials have demonstrated improvements in rates of FN, treatment delays and hospitalization in pts receiving HGFs, although no improvement in remission or survival rates has been observed. We undertook a systematic review of published evidence relating to the use of HGFs (G-CSF and GM-CSF) as primary prophylaxis for FN in the management of ML pts. The searches covered Medline, Embase, Cancerlit, Cochrane and NEED databases, the UKCCCR trials register and the publication databases of the European Haematology Association and American Society of Hematology websites. Only randomized controlled trials published in peer-reviewed journals were included. Publications were excluded if <80% of the study population were lymphoma pts. The relative risk comparing the proportion of pts administered HGF compared to controls for specified outcome measures, and the 95% confidence intervals were calculated for each trial and then combined using a weighted average. Six randomized trials were identified that compared growth factors with no additional therapy or placebo. Results of the analyses are tabulated below: outcome measure noofstudies noofpts weighted relative risk (95% CD 5 year survival 2 236 1.15(0.83,1.60) complete remission 5 583 1.07(0.87,1.32) neutropenia (ANC <0.5) 3 391 0.56(0.42,0.74) infection 6 637 0.57 (0.42, 0.77) Hospitalization due to infection 2 321 0.40(0.21,0.77) treatment delays (any reason) 2 252 0.40 (0.24, 0.69) treatment delays (neutropenia) 2 242 0.20(0.10.0.41) weighted ratio duration of hospitalization 4 450 0.53 There was no evidence of an effect of HGFs on survival or complete remission rates. There was a significant reduction (p<0.01 ) in all other outcome measures. These results suggests that the benefits of HGFs in this context are restricted to endpoints related to FN rather than disease control. A cost-effectiveness analysis utilizing these data is in progress.