The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy

Philip S. Rosenberg, Blanche P. Alter, Audrey A. Bolyard, Mary Ann Bonilla, Laurence A. Boxer, Bonnie Cham, Carol Fier, Melvin Freedman, George Kannourakis, Sally Kinsey, Beate Schwinzer, Connie Zeidler, Karl Welte, David C. Dale

Research output: Contribution to journalArticlepeer-review

Abstract

In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.9% per year. The hazard of MDS/AML increased significantly over time, from 2.9% per year after 6 years to 8.0% per year after 12 years on G-CSF. After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML. A subgroup of SCN patients (29%) received more than the median dose of G-CSF (≥ 8 μg/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC <2.188 × 109/L [2188/μL] at 6-18 months). In these less-responsive patients, the cumulative incidence of adverse events was highest: after 10 years, 40% developed MDS/AML and 14% died of sepsis, compared with 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Risk of MDS/AML may be similar in SDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option.

Original languageEnglish (US)
Pages (from-to)4628-4635
Number of pages8
JournalBlood
Volume107
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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