羟基脲治疗镰状细胞贫血患儿脾脏功能保留的预测因素

Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

作者信息

Nottage Kerri A, Ware Russell E, Winter Bryan, Smeltzer Matthew, Wang Winfred C, Hankins Jane S, Dertinger Stephen D, Shulkin Barry, Aygun Banu

机构信息

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.

出版信息

Eur J Haematol. 2014 Nov;93(5):377-83. doi: 10.1111/ejh.12361. Epub 2014 Jun 2.

DOI:10.1111/ejh.12361

PMID:24796940

Abstract

BACKGROUND

More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function.

METHODS

Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc(99) m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, <10% uptake, decreased but ≥10% uptake, and normal.

RESULTS

Mean age (N = 40) was 9.1 yrs, range 2.3-17.0. After 3 yrs of treatment, 13 (33%) had uptake on LS scan. These 13 children were younger (median age 6.0 vs. 10.6 yrs, P = 0.008), had a higher HbF at baseline (mean 10.2% vs. 5.8%, P = 0.004) and after 3 yrs (22.9% vs. 13.9%, P < 0.001), achieved MTD more rapidly (median 288 vs. 358 d, P = 0.021), and were more likely to have baseline splenic uptake (P < 0.001).

CONCLUSIONS

Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome.

摘要

背景

超过90%的镰状细胞贫血（SCA）患儿在2岁时失去脾脏功能。羟基脲可能改善脾脏功能，但既往研究结果相互矛盾。我们前瞻性评估了羟基脲对脾脏滤过功能的影响。

方法

参与羟基脲长期效应研究（HUSTLE，NCT00305175）的SCA患儿在开始使用羟基脲前及治疗3年至最大耐受剂量（MTD）后接受了包括Tc（99）m肝脾（LS）扫描在内的临床评估。LS扫描分类如下：无摄取、摄取<10%、摄取减少但≥10%以及正常。

结果

平均年龄（N = 40）为9.1岁，范围为2.3 - 17.0岁。治疗3年后，13例（33%）LS扫描有摄取。这13例患儿年龄更小（中位年龄6.0岁对10.6岁，P = 0.008），基线时HbF更高（平均10.2%对5.8%，P = 0.004），3年后也更高（22.9%对13.9%，P < 0.001），达到MTD更快（中位时间288天对358天，P = 0.021），且更可能基线时有脾脏摄取（P < 0.001）。