The Use of Pegylated G-CSF in Chronic Neutropaenia of Childhood. A Single Centre Experience

Abstract ³²⁶⁸

Chronic Neutropenia of Childhood (CNC) is defined as an absolute neutrophil count that is persistently below 0.5×10⁹/L and leaves patients at risk of severe, systemic bacterial and fungal infections. The standard treatment to raise the neutrophil count is daily injections of recombinant G-CSF to maintain the neutrophil count above 1.0 × 10⁹/L and the child infection free.

A long acting Pegylated G-CSF (PEG G-CSF) is available but is unlicensed for use in chronic neutropenia and in children. Concern has been expressed regarding long term exposure to PEG G-CSF and the potential for neutralising antibodies; there is a lack of clinical evidence and experience in its use for CNC. Potential advantages exist in its use including a more stable and sustained neutrophil count and fewer subcutaneous injections; the latter an important consideration in a paediatric population.

We report a single centre experience of seven consecutive cases using PEG G-CSF in CNC. Five boys and two girls age range five months to six years had a total of thirty four presentations in Accident and Emergency for bacterial infection; eleven episodes required hospital admission and intravenous antibiotics. All had a history of persistent neutropenia ranging from one to thirty two months. Prophylactic oral anti-infectives; ciprofloxacin and itraconazole were prescribed and once bone marrow examination had excluded evidence for other causes of persistent neutropenia standard G-CSF was commenced.

All seven patients were responsive to G-CSF and so following two – four weeks of treatment a switch to PEG G-CSF was made. Neutrophil response kinetics was monitored to tailor individual dose and frequency of injections.

In all cases there was an increased longevity of neutrophil response over time. Treatment with PEG G-CSF was required initially every seven days, but the neutrophil count was ultimately sustained by one injection every three to four weeks. We hypothesise that this is due to gradual recruitment of immature precursors and stem cells towards the neutrophil lineage; whereas the initial neutrophil responses are the result of more mature committed precursors.

Once on PEG G-CSF there was a marked reduction in serious bacterial infections with a total of only six urgent medical assessments sought. This resulted in one admission each for three of the children. Four children had no further hospital admissions.

The neutrophil count responded and was maintained in all seven cases. Prophylactic anti-infectives were discontinued once a stable neutrophil count was achieved. Six patients continued the PEG G-CSF successfully whilst one discontinued its use due to maternal concerns of an associated behaviour change and sleep disturbance, not an expected side effect of PEG G-CSF.

These cases demonstrate the effective, safe use of PEG G-CSF in chronic neutropenia of childhood, with a more sustained neutrophil count and thus reduced risk of infection. There was no evidence of a reduced response to PEG C-CSF suggesting no development of neutralising antibodies.

The decreased frequency of injections has led to an improved quality of life for these children and their families, with fewer hospital visits for treatment, blood sampling and review.