The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy.
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 (> or = 8 microg/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/microL] 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.
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852-7244, USA. rosenbep@mail.nih.gov
Philip S
PS
Rosenberg
Blanche P
BP
Alter
Audrey A
AA
Bolyard
Mary Ann
MA
Bonilla
Laurence A
LA
Boxer
Bonnie
B
Cham
Carol
C
Fier
Melvin
M
Freedman
George
G
Kannourakis
Sally
S
Kinsey
Beate
B
Schwinzer
Connie
C
Zeidler
Karl
K
Welte
David C
DC
Dale
D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D007958:Leukocyte Count; D008297:Male; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D009503:Neutropenia / Q000097:blood / Q000150:complications / Q000151:congenital / Q000188:drug therapy / Q000401:mortality*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D015996:Survival Rate
D016179:Granulocyte Colony-Stimulating Factor