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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4628-4635. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-11-4370. This Article Full Text (PDF) All Versions of this Article: 2005-11-4370v1 107/12/4628    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rosenberg, P. S Articles by Dale, D. C Search for Related Content PubMed PubMed Citation Articles by Rosenberg, P. S Articles by Dale, D. C Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 4, 2005 Accepted February 3, 2006 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 A Bonilla, Laurence A Boxer, Bonnie Cham, Carol Fier, Melvin Freedman, George Kannourakis, Sally Kinsey, Beate Schwinzer, Connie Zeidler, Karl Welte, and David C Dale Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute, Rockville, MD, USA Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, Rockville, MD, USA Department of Medicine, University of Washington, Seatlle, WA, USA Department of Pediatric Hematology Oncology, St. Joseph's Children's Hospital, Paterson, NJ, USA Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, MI, USA CancerCare Manitoba, Winnipeg, MB, Canada Amgen, Inc., Boulder, CO, USA Hospital for Sick Children, Toronto, ON, Canada Ballarat Onc. & Haem. Services, Wendouree, Australia St. James's University Hospital, Leeds, United Kingdom Kinderklinic, Medizinische Hochschule, Hannover, Germany * Corresponding author; email: rosenbep{at}mail.nih.gov. In patients with severe congenital neutropenia (SCN), mortality from sepsis is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported in treated and untreated patients. 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, mortality from sepsis was stable at 0.9%/year. The hazard of MDS/AML increased significantly over time, from 2.9%/year after 6 years to 8.0%/year after 12 years on G-CSF. After 10 years, the cumulative incidence was 8% for mortality from sepsis and 21% for MDS/AML. The hazard of MDS/AML increased with the dose of G-CSF. Twenty-nine percent of SCN patients received more than the median dose of G-CSF (8 µg/kg/day), but achieved less than the median absolute neutrophil count (ANC) response (ANC <2188 cells/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 to 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Available data do not suggest that the risk of MDS/AML is lower in SDS than in SCN. In the less responsive patient with SCN, early hematopoietic stem cell transplantation may be a rational option. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Reconsidering how we treat severe congenital neutropenia Kevin Shannon Blood 2006 107: 4575-4576. [Full Text] [PDF] This article has been cited by other articles: K. Beel and P. 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