D. Dale, M.A. Bonilla, L. Boxer, M. Freedman, S. Brown, C. Fier, and K. Welte, for the SCN International Disease Registry, Seattle, WA, Hannover, Germany, and Amgen, Thousand Oaks, CA. 1994.

Pts with SCN as a result of congenital neutropenia (CN), cyclic neutropenia (CyN), or idiopathic neutropenia (IN), all states due to disorders of neutrophil production, experience infections resulting in considerable morbidity and mortality. To stimulate neutrophil production, r-metHuG-CSF was tested in a randomized, controlled Phase III trial. Benefits included a reduction in fever, mucositis, the incidence/duration of infections, the duration of antibiotic use, and improvement in the quality of life. Worldwide clinical trials with r-metHuG-CSF provide information on the rx of 325 pts: CN-185 pts, CyN-48 pts, IN-74 pts, and Other-18pts. Pts have been treated for up to 7 years with varying doses of drug to titrate neutrophil levels. Adverse effects have been similar to those identified in the Phase III trial, including bone pain, rash, and splenomegaly. Prior to the era of growth factors, reports describe pts with CN who developed AML, suggesting that CN may be a premalignant condition. From current trials, nine cases (7AML, 2 MDS) have been reported in pts with CN, eight with monosomy 7 (median 44 mo rx, range 22-73.5 mo). Five pts had prior normal cytogenetic studies; four pts had no earlier studies. No relationship was seen with dose/duration of dosing with r-metHug-CSF. Nine other pts have presented with a variety of cytogenetic abnormalities on routine BM exam, w/o evidence of MDS or AML to date (median 52 mo rx, range 18-74.5 mo). These include 6 pts with CN [2(del7), 1(inv5), 1(inv16), 1(del2), 1t(x;5)], 2 pts with IN [1(trisomy8), 1(5q-1)], and 1 pt with CyN [inv(8), repeat study 2.5 mo later normal]. From this second group, 5/9 pts continue on treatment with r-metHuG-CSF. An SCN International Registry has been established to study these rare disorders and the efficacy and safety of long term rx.

For more information on MDS and AML, see the article Myelodysplastic Syndromes.