Rosenberg Philip S, Alter Blanche P, Bolyard Audrey A, Bonilla Mary Ann, Boxer Laurence A, Cham Bonnie, Fier Carol, Freedman Melvin, Kannourakis George, Kinsey Sally, Schwinzer Beate, Zeidler Connie, Welte Karl, Dale David C
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852-7244, USA.
Blood. 2006 Jun 15;107(12):4628-35. doi: 10.1182/blood-2005-11-4370. Epub 2006 Feb 23.
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.
在严重先天性中性粒细胞减少症（SCN）患者中，使用粒细胞集落刺激因子（G-CSF）治疗可降低败血症死亡率，但已有骨髓增生异常综合征和急性髓系白血病（MDS/AML）的报道。我们研究了374例SCN患者和29例施瓦茨曼-戴蒙德综合征（SDS）患者，这些患者长期接受G-CSF治疗并被纳入严重慢性中性粒细胞减少症国际注册研究。在SCN患者中，败血症死亡率稳定在每年0.9%。MDS/AML的风险随时间显著增加，在接受G-CSF治疗6年后为每年2.9%，12年后为每年8.0%。10年后，败血症死亡率的累积发生率为8%，MDS/AML为21%。SCN患者的一个亚组（29%）接受的G-CSF剂量超过中位数（≥8μg/kg/d），但其绝对中性粒细胞计数（ANC）反应低于中位数（6至18个月时ANC<2.188×10⁹/L[2188/μL]）。在这些反应较差的患者中，不良事件的累积发生率最高：10年后，40%发生MDS/AML，14%死于败血症，而反应较好、ANC高于中位数且G-CSF剂量低于中位数的患者中，这两个比例分别为11%和4%。SDS和SCN患者发生MDS/AML的风险可能相似。对于反应较差的SCN患者，早期造血干细胞移植可能是一个合理的选择。
