The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy
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DOI：
10.1182/blood-2005-11-4370
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Dale, David C.
中科院分区：
文献类型：
--
作者：
Rosenberg, Philip S.;Alter, Blanche P.;Dale, David C.
在严重先天性中性粒细胞减少症（SCN）患者中，用粒细胞集落刺激因子（G-CSF）治疗可降低败血症死亡率，但髓系增生综合征和急性髓系白血病（MDS/AML）也有报道。我们研究了374名SCN患者和29名长期服用G-CSF的Shwachman-Diamond综合征（SDS）患者，这些患者登记在严重慢性中性粒细胞减少症国际登记处。在SCN中，败血症死亡率稳定在每年0.9%。随着时间的推移，MDS/AML的风险显著增加，从6年后的每年2.9%增加到G-CSF 12年后的每年8.0%。10年后，败血症死亡率的累积发生率为8%，MDS/AML的累积发生率为21%。SCN患者的一个亚组（29%）接受了超过中位剂量的G-CSF (！8 μ g/kg/d)，但低于中位绝对中性粒细胞计数（ANC）反应（6-18个月时ANC < 2.188 × 10(9)/L [2188/ μ L]）。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%的患者发展为MDS/AML， 14%的患者死于败血症，而在G-CSF低于中位数剂量的情况下，ANC高于中位数的反应较好的患者分别为11%和4%。小岛屿发展中国家和SCN的MDS/AML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。
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 mu g/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/mu L] 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 SIDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option.