European Society for Paediatric Research Abstract

IMPROVED SURVIVAL FROM GRANULOCYTE-COLONY STIMULATING FACTOR THERAPY FOR CONGENITAL NEUTROPENIA UNMASKS PREDISPOSITION TO MYELODYSPLASIA AND ACUTE MYELOID LEUKEMIA

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Results. The 302 patients with congenital neutropenia were observed on G-CSF treatment for a mean of five years (range 0.1 to 10 years). Twenty-seven developed MDS/AML giving a crude rate of malignant transformation of nine percent at mean follow-up of five to six years. Twenty-six had congenital neutropenia (Kostmann's syndrome) and one had Shwachman-Diamond syndrome. None of the patients with idiopathic or cyclic neutropenia for whom similar data were maintained and analyzed developed MDS/AML. Conversion to MDS/AML was frequently associated with acquired marrow cytogenetic clonal changes: 14 developed partial or complete loss of chromosome 7, and nine manifested abnormalities of chromosome 21 (usually trisomy 21). Eight other patients also acquired marrow clonal cytogenetic changes but without evolution to MDS/AML during an observation period of up to 74 months. Life table analyses showed that the hazard rates for MDS/AML for each yearly interval were less than two percent per year in most instances. Statistical treatment of the data did not show a significant relationship to any of the following: patient gender, age of onset of MDS/AML, dose of G-CSF compared to age of onset of MDS/AML, dose of G-CSF in patients with and without MDS/AML, or on duration of treatment with G-CSF (p values for all >0.15).

Conclusion. In the pre-cytokine era there were reports of MDS/AML developing spontaneously in patients with congenital forms of neutropenia indicating a propensity for malignant myeloid transformation. Our data do not support a cause-and-effect relationship between development of MDS/AML and G-CSF dose or duration of therapy in congenital neutropenia, nor with any other patient demographics. It is likely that the improved survival of congenital neutropenia patients with G-CSF therapy allows time for the expression of the leukemic predisposition that characterizes the natural history of these disorders.

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Freedman, M., Bonilla, M., Fier, C. et al. IMPROVED SURVIVAL FROM GRANULOCYTE-COLONY STIMULATING FACTOR THERAPY FOR CONGENITAL NEUTROPENIA UNMASKS PREDISPOSITION TO MYELODYSPLASIA AND ACUTE MYELOID LEUKEMIA. Pediatr Res 45, 942 (1999). https://doi.org/10.1203/00006450-199906000-00267

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