Management of Kostmann syndrome in the G-CSF era.

Kostmann (1956, 1975) described an inherited haematological disorder with severe neutropenia with an absolute neutrophil count (ANC) , 0 ́2 10/l and early onset of severe bacterial infections. Most children died because of these infections, despite antibiotic treatment. Different treatment strategies for congenital neutropenia (CN) included use of steroids and lithium (Barrett et al, 1977; Hraker et al, 1977), but these treatments did not show any long-term effect on neutrophil counts. Bone marrow transplantation (BMT) was the only curative treatment option for patients with human leucocyte antigen (HLA)compatible donors (Rappeport et al, 1980). Some patients who survived infections and treatment, however, underwent malignant transformation into acute myeloid leukaemia (AML) (Gilman et al, 1970; Rosen & Kang, 1979). The availability of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in 1987 (Nagata et al, 1986; Souza et al, 1986) dramatically changed both the prognosis of CN and the quality of life for patients with CN (Bonilla et al, 1989; Welte et al, 1990). Since the establishment of the Severe Chronic Neutropenia International Registry (SCNIR) in 1994, data on 304 patients with CN have been collected to monitor the clinical course, treatment and disease outcomes in these patients. In clinical trials, . 90% of these patients responded to rHuG-CSF treatment with an increase in ANC . 1 ́0 10/l. Importantly, all responding patients required significantly fewer antibiotics and days of hospitalizations (Dale et al, 1993; Bonilla et al, 1994; Welte & Dale, 1996; Freedman, 1997; Welte & Boxer, 1997). Haematopoietic stem cell transplantation (HSCT) remains the only currently available treatment for those patients refractory to rHuG-CSF treatment that continue to have severe and life-threatening bacterial infections. Data from the SCNIR also demonstrate that for all CN patients, < 9% will develop leukaemia regardless of their treatment or response (Bonilla et al, 1994; Freedman, 1997; Welte & Boxer, 1997). The molecular and genetic basis for this disease is still largely unknown.