Colony-stimulating factors, in particular granulocyte colonystimulating factor (G-CSF), are widely used for the amelioration of chemotherapy-induced neutropenia. There is a paucity of data regarding the safety of G-CSF in patients with sickle cell anemia. This is relevant, as neutrophil activation may be involved in the pathogenesis of sickle crises. Here we report a patient with sickle cell/thalassemia who developed a sickle cell crisis and lifethreatening multiorgan failure in close temporal relationship to administration of G-CSF.

A 58-year-old Greek female with stage II invasive ductal breast carcinoma underwent bilateral mastectomies and was scheduled to commence adjuvant chemotherapy with 150 mg cyclophosphamide orally alternating with 200 mg orally daily for a total of 14 days, 70 mg methotrexate intravenously on days 1 and 8, and 1050 mg 5-fluorouracil intravenously on days 1 and 8 (CMF). The cycle was to be repeated each 28 days. The patient’s history included several episodes of lower back pain requiring narcotic analgesia in the preceding 2 years. Prior to starting chemotherapy, she had a normal hemoglobin (120 g/L; normal range, 115-150 g/L), microcytosis (mean corpuscular volume, 71 fL; range, 80-96 fL), and mild thrombocytopenia (platelets, 137 109/L; range, 140-400 109/L). An abdominal ultrasound revealed a bulky spleen. Liver function tests were normal. The serum ferritin level was 16 g/L (range, 20-120 g/L). Hemoglobin electrophoresis revealed an abnormal band migrating as Hb S amounting to 57% of the total hemoglobin. The solubility test for Hb S was positive. DNA testing revealed compound heterozygosity of Hb S with a mutation involving intron 1, position 6. The only sibling, a sister, had an Hb S level of 36%, consistent with sickle cell trait. There were no other surviving first-degree relatives. The first chemotherapy cycle was administered without G-CSF and proceeded uneventfully except for mild chemotherapy-induced neutropenia (neutrophil nadir of 1.1 109/L on day 17). On day 9 of the second cycle, subcutaneous injections each morning of 480 g r-metHuG-CSF (filgrastim, Neupogen, Amgen, Australia) were commenced. On the night after the fourth dose, the patient complained of severe lower back pain, along with dyspnea and drowsiness. Pain and respiratory distress worsened significantly following the next morning’s dose, resulting in admission to the hospital. Severe hypoxia (arterial oxygen saturation, 70%), unresponsive to supplemental oxygen therapy, required endotracheal intubation and mechanical ventilation. A chest x-ray showed bilateral pulmonary infiltrates. A ventilation/perfusion lung scan demonstrated low probability for pulmonary embolism. Full blood examination revealed marked anemia: hemoglobin, 54 g/L; white cell count, 6.4 109/L; and platelets, 95 109/L. Blood film revealed a mild increase in the number of sickle cells compared to the prechemotherapy film. Anisopoikilocytosis, myeloid left shift, and toxic change were consistent with G-CSF. Blood cultures were repeatedly negative. There was widespread organ dysfunction with evidence of myocardial ischemia: troponin I level 28.9 g/L (range, 0.4/L) and creatine kinase 333 IU/L (range, 20-160 IU/L); renal impairment: creatinine