E. Yakisan, C. Zeidler, E. Schirg, A. Reiter, B. Koci, C. Fier, H. Riehm and K. Welte., Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany, and Amgen, Thousand Oaks, CA. 1994.

Severe congenital neutropenia (Kostmann’s syndrome) is an autosomal recessive disease characterized by persistent severe absolute neutropenia (<500 cells/u l) associated with severe bacterial infections. In our clinic 32 patients (age 0-23 years) with confirmed diagnosis of congenital neutropenia were treated with r-metHuG-CSF (G-CSF, Filgrastim). 30 of 32 patients responded to G-CSF with a sustained (up to six years) increase in absolute neutrophil counts (ANC) to above 1000 cells/u l. The quality of life of these patients has been improved dramatically. G-CSF has been well tolerated by majority of the patients. Clinical observations of bone pain, pathological fractures in two patients and osteoporosis in X-ray films led us to assess the bone mineral density and mineral status in more detail in 20 patients (11 female, 9 male). Presence of osteopenia/osteoporosis was evaluated either by X-ray examination of the lumbar vertebrae (n=7), or by quantitative computed tomography (Q-CT) (n=4), or Q-CT plus lumbar x-ray (n=9). In 10 of these patients the bone mineral content was severely diminished (more than 2 SD below normal). Prior to G-CSF treatment at least 6 of these patients showed in roentgenogramms of the lumbar vertebrae osteopenia/osteoporosis. Unfortunately, the other 4 patients with osteopenia/osteoporosis were not tested prior to treatment. In 5 patients with osteopenia/osteoporosis sequential Q-CT analysis were performed yearly, of which in 2 bone density decreased during treatment, 3 remained stable. The serum biochemical markers of bone metabolism were within normal ranges except for mild elevation of serum alkaline phosphatase. The degree of spinal bone mineral loss did not correlate with the G-CSF dosage and treatment duration, patients age or sex. The underlying pathogenesis of bone demineralization is not yet clear. The presence of osteopenia/osteoporosis prior to G-CSF treatment in 6 patients makes it very likely that it is a symptom of the underlying disease and most likely not caused by G-CSF treatment.

For more information on Severe congenital neutropenia, see the articles What is Neutropenia? and Types of Severe Chronic Neutropenia