Sargramostim

Sargramostim is recombinant human granulocyte-macrophage colony-stimulating factor, produced in yeast. It stimulates neutrophils, monocytes and macrophages and is used after marrow transplantation and induction chemotherapy for acute myeloid leukaemia.

Classification. Haematopoietic growth factor; granulocyte-macrophage colony-stimulating factor.

Mechanism. Binds the granulocyte-macrophage colony-stimulating factor receptor and stimulates proliferation of granulocyte, monocyte and eosinophil lineages, and enhances neutrophil and macrophage function.

Pharmacokinetics. Subcutaneous absorption is rapid; the half-life is about 2 hours intravenously and 2 to 3 hours subcutaneously. Leucocytes rise within 3 to 6 days.

Neutrophil recovery after induction chemotherapy for acute myeloid leukaemia (adults 55 years and older).

• Dose: 250 µg/m² daily by intravenous infusion over 4 hours, starting about day 11 or 4 days after induction, only if the day-10 marrow is hypoplastic with less than 5% blasts. Continue until neutrophils exceed 1.5 × 10⁹/L for 3 days, up to 42 days.

Neutrophil recovery after autologous or allogeneic marrow transplant.

• Dose: 250 µg/m² daily by intravenous infusion over 2 hours, starting 2 to 4 hours after marrow infusion and at least 24 hours after the last chemotherapy and 12 hours after radiotherapy. Continue until neutrophils exceed 1.5 × 10⁹/L for 3 days.

Peripheral blood progenitor cell mobilisation. 250 µg/m² daily by intravenous infusion over 24 hours or subcutaneously, continued through apheresis.

Graft failure or delayed engraftment. 250 µg/m² daily for 14 days intravenously over 2 hours; may repeat after 7 days off at 500 µg/m² daily.

Maximum and titration. Reduce the dose by half or stop if neutrophils exceed 20 × 10⁹/L or platelets exceed 500 × 10⁹/L. No loading dose.

Adjustments. Kidney and liver: no formal adjustment; monitor creatinine and bilirubin. Children: the same dose by body surface area.

Contraindications. Excessive leukaemic blasts (10% or more) in marrow or blood, hypersensitivity to yeast-derived products, and use within 24 hours before or after cytotoxic therapy or 12 hours of radiotherapy.

Adverse effects. Fever, bone pain, myalgia, fluid retention with pleural or pericardial effusion, capillary leak, supraventricular arrhythmia, and a first-dose reaction (flushing, dyspnoea, tachycardia, hypotension, hypoxia).

Interactions. Lithium and corticosteroids may potentiate leucocytosis. Concurrent use with cytotoxics is avoided.

Pregnancy and breastfeeding. Limited data; use only if benefit outweighs risk.

Regional points. Availability is limited in much of East Africa; filgrastim is more widely used.

Common errors. Starting too close to chemotherapy; continuing after recovery.

Administration. Intravenous infusion in 0.9% sodium chloride, or subcutaneous injection. Do not use an in-line membrane filter. Store at 2 to 8°C.

Baseline. Full blood count with differential, weight, fluid status, chest film if respiratory disease.

Monitoring. Full blood count with differential at least twice weekly; weight and fluid balance; respiratory status.

Referral and escalation. Stop for severe first-dose reaction or leucocytosis above 20 × 10⁹/L; assess for capillary leak.