Granulocytosis typically accompanies episodes of painful crises and acute chest syndrome in sickle-cell disease, although a causal association between granulocytosis and these complications has not been established. During studies directed at developing gene therapy for sickle-cell disease, we sought to identify a safe and effective means of mobilising early haematopoietic cells into the circulation of patients with granulocyte-colony stimulating factor (G-CSF). A 34-year-old African American woman with sickle-cell anaemia required hospital admission two to four times a year for treatment of painful crises. A trial of hydroxyurea was discontinued due to concerns about compliance. She had never had an acute chest syndrome. Recombinant human GCSF (Amgen, Thousand Oaks, CA, USA) was given as a single daily subcutaneous injection at a dosage of 2.5 pgkg. Blood counts, circulating clonogenic progenitors and, circulating CD34+ cells were measured daily. Within 12 hours of the first injection, white blood cells (WBCs) rose five-fold, due almost exclusively to an increase in neutrophils. On the morning of the third study day, she developed pain in her arms, chest, upper abdomen, and legs which she described as identical to her usual sickle-cell crisis. The severity of her pain matched the worst crisis she had ever had. WBCs were 63.4 X 1 09L Chest radiograph showed bilateral infiltrates consistent with an acute chest syndrome. No further G-CSF was given and hydroxyurea, 2 g, was given by mouth. Within 12 hours, WBCs had decreased and her symptoms began to improve. A second dose of hydroxyurea (1 5 g) was given. A further decline in WBCs was associated with marked clinical improvement and she was discharged on day 7. Repeat chest radiograph showed near-complete resolution of the pulmonary infiltrates. Neither circulating progenitor cells nor CD34+ cells rose when GCSF was given, however, both increased on day 7, 3-4 days after hydroxyurea.

The development of gene therapy for sickle-cell disease will require procedures for the procurement of stem cells. Our experience shows that G-CSF alone is not safe. This case also suggests the possibility of a causal link between granulocytosis and sickle-cell crises. Leucocytosis has been associated with an increased frequency of pain crises in a large populationbased study: and hydroxyurea appears to be most effective in individuals who experience the greatest reduction in WBCS.~~~ This reduction in WBCs by hydroxyurea may explain cases in which clinical benefit has been observed in the absence of sigdicant elevations in fetal haemoglobinP In this woman, there was prompt improvement in symptoms as her granulocytosis resolved, suggesting that interventions that reduce granulocytosis may warrant investigation in clinical trials.