Long-Term Effects of G-CSF Use in Patients With Cyclic Neutropenia

Based on long-term observations, granulocyte colony-stimulating factor utilization (G-CSF) is a safe and effective treatment to prevent infections and improve quality of life in patients with cyclic neutropenia, according to an analysis in The New England Journal of Medicine.

Cyclic neutropenia is characterized by regular oscillations in neutrophil counts from normal levels (>1.5×10⁹ per liter) to severe neutropenia (<0.2 ×10⁹ per liter), with a cycle length of approximately 21 days. Cyclic neutropenia is usually caused by mutations in the gene encoding neutrophil elastase (ELANE). Patients with cyclic neutropenia usually suffer from fevers and mouth ulcers and are at risk for severe infections.

The authors of the analysis originally analyzed the administering of G-CSF in patients with cyclic neutropenia 28 years ago, and reported that randomized clinical trial results showed G-CSF use prevented infections in those patients. Following the trial, the authors followed the 6 patients and 350 others: 239 were followed through the Severe Chronic Neutropenia International Registry (SCNIR), which documents treatments, serious infections, hospitalizations, cancers, and deaths; 112 were family members with cyclic neutropenia; and 5 were listed as other.

At the time of the long-term analysis, the authors reported that the 6 patients from the original study were between ages 38 and 94, and 5 had ELANE mutations. The patient without the mutation had significant improvement and stopped the G-CSF; the remaining 5 patients continually maintained good health while receiving the G-CSF injections at least 3 times per week for nearly 30 years. One of the patients had decreased bone density, and one patient developed idiopathic thrombocytopenic purpura; otherwise there were no clinically significant complications.

Among the 239 patients followed through the SCNIR, there was a consistent history of recurrent fevers, mouth ulcers, and infections before they began their G-CSF. The authors observed 18 episodes of severe infection in patients who were not receiving G-CSF and 2 episodes in patients who were receiving G-CSF.

“Since our original report, we have recorded nearly 3000 patient-years of treatment with G-CSF,” wrote the authors. “On the basis of these long-term observations, we believe that G-CSF is a remarkably safe and effective treatment to prevent infections and improve the quality of life in patients with cyclic neutropenia.”