A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy.
A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy.
复制标题
DOI：
10.1002/ajh.24906
复制
发表时间：
2017-12
影响因子：
12.8
通讯作者：
Hankins JS
中科院分区：
文献类型：
--
作者：
Estepp JH;Smeltzer MP;Kang G;Li C;Wang WC;Abrams C;Aygun B;Ware RE;Nottage K;Hankins JS
羟基脲已被证明具有临床益处，建议所有镰状细胞性贫血 (SCA) 儿童使用，但最佳剂量方案仍存在争议。羟基脲对红细胞胎儿血红蛋白 (HbF) 的诱导似乎具有剂量依赖性。然而，最大化 HbF% 是否可以改善临床结果尚不清楚。 HUSTLE (NCT00305175) 是一项前瞻性观察性研究，主要目标是描述羟基脲升级至最大耐受剂量 (MTD) 对 SCA 儿童的长期临床效果。对 230 名儿童进行了 610 患者年的随访，在长达 4 年的随访中，MTD 时平均达到的 HbF% >20%。当 HbF% 值≤20%时，儿童因任何原因住院的几率是两倍（p<0.0001），包括血管闭塞性疼痛（p<0.01）和急性胸部综合征（ACS）（p<0.01），因发烧入院的几率是四倍多（p<0.001）。 30 天再入院率不受 HbF% 的影响。中性粒细胞减少症 (ANC <1,000×106/L) 罕见（占所有实验室监测的 2.3%）、短暂且良性。因此，HbF 达到 >20% 与住院次数减少相关，且无明显毒性。这些数据支持在儿童中使用羟基脲，并表明首选剂量策略是针对 HbF 终点 >20% 的策略。
Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow-up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (p<0.0001), including vaso-occlusive pain (p<0.01) and acute chest syndrome (ACS) (p<0.01), and more than four times the odds of admission for fever (p<0.001). Thirty day readmission rates were not affected by HbF%. Neutropenia (ANC <1,000×106/L) was rare (2.3% of all laboratory monitoring), transient, and benign. Therefore, attaining HbF >20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%.
登录
查看更多内容
影响因子：
6.5
作者：
de Castro Lobo, Clarisse Lopes;Pinto, Jorge F. C.;Hankins, Jane S.
通讯作者：
Hankins, Jane S.
影响因子：
3.1
作者：
Nottage, Kerri A.;Ware, Russell E.;Aygun, Banu
通讯作者：
Aygun, Banu
影响因子：
8.6
作者：
Grosset, KA;Bone, I;Grosset, DG
通讯作者：
Grosset, DG
影响因子：
12.8
作者：
Ballas, Samir K.;Lieff, Susan;Benjamin, Lennette J.;Dampier, Carlton D.;Heeney, Matthew M.;Hoppe, Carolyn;Johnson, Cage S.;Rogers, Zora R.;Smith-Whitley, Kim;Wang, Winfred C.;Telen, Marilyn J.
通讯作者：
Telen, Marilyn J.
影响因子：
20.3
作者：
Almeida, Camila Bononi;Botelho Souza, Lucas Eduardo;Conran, Nicola
通讯作者：
Conran, Nicola