Bohlius, J., Herbst, C., Reiser, M., Schwarzer, G., & Engert, A. (2008). Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database of Systematic Reviews, 4, CD003189.

The purpose of this study was to determine the effectiveness of G-CSF and GM-CSF in patients with malignant lymphomas for improving overall survival (OS) and freedom from treatment failure (FFTF). Secondary goals were to to decrease the risk and duration of neutropenia and febrile neutropenia, infection and mortality during chemotherapy; improve received dose intensity, tumor response, and quality of life; and examine adverse effects.

Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Medikat, Russmed Articles, SOMED, Toxline, BIOSIS Previews, and LILACS databases were used.

In addition, Internet databases of grey literature (SIGLE) and ongoing trials were reviewed, as were conference proceedings. Experts and pharmaceutical companies also were contacted for unpublished or ongoing trials. Citations of identified trials also were searched.

Key words included granulocyte–colony-stimulate factor (G-CSF), granulocyte-macrophage–colony-stimulating factor (GM-CSF), malignant lymphoma
 
Studies were included if they were randomized, controlled trials (RTCs) conducted from January 1980 to April, 2008 comparing G-CSF or GM-CSF prophylaxis with placebo or no prophylaxis; studies on long-lasting G-CSFs (e.g., filgrastim) also were included. Abstracts and unpublished data were included if enough data were available on study design, patient characteristics, interventions, and outcomes.
 

Studies were excluded if they were crossover studies, quasi-randomisedand, or nonrandomised comparative studies.

306 total abstracts were reviewed. Of these, 90 studies were evaluated and 74 excluded for not meeting inclusion criteria. The remaining 16 RTCs met inclusion criteria, but three of these were later excluded due to not fulfilling all criteria.

Subgroup analysis and investigation of heterogeneity (drug type: G-CSF versus GM-CSF; Hodgkin disease versus non-Hodgkin lymphoma; age [trials that included all ages 16 and older versus those restricted to older than age 60 years]; administration of prophylactic antibiotics during chemotherapy; different toxicity of chemotherapies); sensitivity analysis (placebo-controlled versus open label; concealment of allocation; size of studies [less than 100 versus 100 or greater]; published versus unpublished, unreported, or abstract based; and duration of follow-up). Statistical analyses included hazard ratios (OS and FFTF) (missing patient data analyzed using published survival curve methods); relative risk and 95% confidence interval (CI) (binary data) using the Mantel-Haenszel method for pooling (pooled using a fixed effect model); continuous data calculated as weighted mean differences with 95% CI; heterogeneity of treatment effect via chi-squared (p < 0.05); robustness of overall results and causes of heterogeneity assessed by sensitivity and subgroup analyses; funnel plots and linear regression (for bias; 0.1 = significant) used for meta-analyses of four or more trials; all data based on intention-to-treat or full set analysis.

• The final sample size included 13 RTCs.
• Total subjects across reviewed studies ranged from 25–784.
• 2,607 randomized patients were included in the review.
• Patients were aged 16 years and older with malignant lymphomas (Hodgkin disease or non-Hodgkin lymphoma) with the histological classifications of Working Formulation, Kiel, REAL, and WHO.
• All participants received standard nonmyeloablative chemotherapeutic agents and either G-CSF or GM-CSF within 72 hours of receiving the chemotherapy and prior to onset of neutropenia in the first or second line treatment of their malignant lymphoma.
• The control groups had to receive the same chemotherapies and same supportive care.

• The phase of care was active treatment
• Application was for elderly care

The prophylactic use of G-CSF or GM-CSF in patients aged 16 years and older with malignant lymphomas who underwent standard chemotherapy treatment had a reduced risk of neutropenia, febrile neutropenia, and infections. The prophylactic use of G-CSF or GM-CSF in this patient population does not increase overall survival or freedom from treatment failure.

Since neutropenia, febrile neutropenia, and infections are prevalent among patients with malignant lymphomas being treated with chemotherapeutic agents, the prophylactic use of G-CSF and GM-CSF is warranted to decrease the risk of these deleterious treatment effects.

Implications for nursing practice include knowledge about the efficacy of using these growth factors, advocating for their use, and close patient monitoring.