Goldschmidt, N., Ganzel, C., Attias, D., Gatt, M., Polliack, A., & Tadmor, T. (2014). Pegfilgrastim prophylaxis for cladribine-induced neutropenia in patients with hairy-cell leukemia. Acta Haematologica, 132, 118–121.

To evaluate the efficacy of primary prophylactic pegfilgrastim compared to on-demand daily G-CSF after treatment with cladribine in patients with hairy-cell leukemia (HCL)

This was a retrospective chart review of 40 patients with HCL (1991–2012) treated with cladribine (0.1 mg/kg per day) for five to seven days either subcutaneously (SC) or IV, receiving a total of 40 courses of therapy treated with filgrastim (300 mcg per day) on demand until the patients' absolute neutrophil counts (ANCs) were > 2.0 x 10⁹ compared to nine courses of therapy with primary pegfilgrastim prophylaxis (6 mg SC for 24 hours after the completion of chemotherapy).

• N = 40 (on-demand filgrastim arm had 31 patients; primary pegfilgrastim prophylaxis arm had nine patients)   
• RANGE AGE = 23–76 years  
• MALES: 80%, FEMALES: 20%
• KEY DISEASE CHARACTERISTICS: HCL diagnosis confirmed by bone marrow biopsy and additional flow cytometry confirmation (after 2004); no significant difference in clinical and laboratory parameters between study populations before therapy including cytopenias, spleen size, ANC, platelet count, hemoglobin count, nadir duration, infections requiring hospitalization, and duration of hospitalization
• OTHER KEY SAMPLE CHARACTERISTICS: The on-demand filgrastim arm included two patients who received three cycles because of relapsed disease, seven patients who were treated with two cycles, and 31 patients who received only one course of therapy. In the primary prophylaxis pegfilgrastim arm, nine consecutive courses were given to nine patients 24 hours after the completion of chemotherapy.

• SITE: Medical centers
• SETTING TYPE: Inpatient  
• LOCATION: Haifa, Israel

• PHASE OF CARE: Active treatment

Retrospective, historical control study of patients with HCL prescribed cladribine determining the effect of IV pegfilgrastim versus filgrastim on neutropenia, hospitalization, 2⁰ FN, severity of infection, and ANC nadir

• The incidence of neutropenia (defined as an ANC < 1.0 x 10⁹ /L)
• Fever (defined as a temperature > 38.2 ^oC)
• Number of days of hospitalization because of FN
• Details of severity of infection
• Number days from the last day of therapy until ANC recovery (defined as an ANC > 1.0 x 10⁹ /L)

The median follow-up was 94 months (range = 12–312 months). No significant difference was found between primary prophylaxis with pegfilgrastim versus on-demand filgrastim for patients with HCL treated with cladribine for the variables of incidence of neutropenia, number days of hospitalization because of FN, severity of infection, or the number of days from the last day therapy till ANC recovery.

This retrospective study demonstrated no difference in the clinical effectiveness of primary pegfilgrastim versus on-demand filgrastim after cladribine therapy for patients with HCL.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: The majority of patients were in the filgrastim group (n = 31) compared to the pegfilgrastim group (n = 9). There may have been differences between the sites that were not disclosed. The grade of neutropenia not described. There were differences between the study groups (relapsed patients in the filgrastim on-demand arm). There were unknown comorbities in study population. Previous patient chemotherapy exposure was unknown. The details of the types and severity of infections post-treatment were not well-reported or described.

This study demonstrated no difference in the incidence of neutropenia, FN, or infections requiring hospitalization between the use of pegfilgrastim versus filgrastim after treatment with cladribine. Large, prospective, randomized trials need to be conducted to validate this study's results. Nurse-sensitive interventions remain critical in the prevention of infection for patients with HCL and prolonged neutropenia caused by disease and treatment.