Novel treatment for severe congenital neutropenia with pegfilgrastim

To the editor:

Severe congenital neutropenia (SCN) of infancy is a rare disorder with onset very early in life. Until the introduction of bone marrow transplantation as a curative strategy, and more recently with the introduction of recombinant granulocyte colony-stimulating factor (G-CSF), this was often a lethal disorder. Although G-CSF has prolonged survival, patients continue to die of infectious complications at a rate of 0.9% per year.¹  Pegfilgrastim, the pegylated, covalent conjugate of G-CSF, is a longer acting form of filgrastim, making once-per-chemotherapy-cycle administration possible. It has been used in adult cancer patients to shorten the duration of chemotherapy-induced neutropenia^2-4  and more recently also as adjuvant treatment in the pediatric population.^5,6  The safety and efficacy profile of pegfilgrastim has been shown to be comparable with filgrastim and, due to its single dose administration, has improved patient quality of life.

We describe the case of an African American female who was found to be neutropenic at 7 weeks of age. A bone marrow aspirate performed at 10 weeks of age showed hypocellularity with decreased myeloid precursor cells and few mature myeloid cells, and she was diagnosed with SCN. Treatment with daily G-CSF was started at 5 months, and until she was 15 and a half years old she received daily G-CSF injections, with average doses of 20 μg/kg/day. Treatment compliance was a major concern, as evidenced objectively by admission and discharge absolute neutrophil count (ANC; Table 1). Since birth, she has been hospitalized 95 times (average of 6 times/year, with a range of 3-11). The average length of stay has been 7 days per admission due to significant infected and unremitting ulcerations and abscesses. At the age of 14 years and 8 months, she developed a right breast abscess that was positive for both methicillin-resistant Staphylococcus aureus and Proteus mirabilis. For the next 10 months, she was hospitalized a total of 53 days for this unremitting lesion and, although she was treated with various antibiotics, the recurrent right breast abscess continued to ulcerate and would not completely heal. At 15 and a half years, she was started on pegfilgrastim at a dose of 3 mg subcutaneously weekly, which was slowly increased to 4.5 mg weekly and then to a maximum of 6 mg subcutaneously weekly. Since starting this regimen 16 months ago, she has been hospitalized 3 times (average hospitalization of 3 days/admission) and the recurrent right breast abscess has completely healed. Pegfilgrastim given once to a 48-year-old patient with SCN has been previously reported,⁷  but to our knowledge, this is the first reported pediatric case of weekly pegfilgrastim usage for the treatment of SCN. Although this is limited to only one case, the treatment has been feasible and well tolerated. Given the fact that survival of patients with SCN has dramatically increased in recent years, we propose that the use of pegfilgrastim can improve quality of life as well as increase compliance, particularly in the adolescent population. Further studies to evaluate long-term outcomes, however, are warranted.