Fung Ellen B, Harmatz Paul, Milet Meredith, Ballas Samir K, De Castro Laura, Hagar Ward, Owen William, Olivieri Nancy, Smith-Whitley Kim, Darbari Deepika, Wang Winfred, Vichinsky Elliott
Department of Hematology, Children's Hospital & Research Center, Oakland, California, USA.
Am J Hematol. 2007 Apr;82(4):255-65. doi: 10.1002/ajh.20809.
A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.
对142名地中海贫血患者（Thal）、199名接受输血的镰状细胞病患者（Tx-SCD，n = 199）和64名未接受输血的镰状细胞病患者进行了一项自然史研究，以描述铁相关发病和死亡的频率。从美国、加拿大或英国的31个中心招募的受试者在年龄（总体：25±11岁，平均值±标准差）和性别（52%为女性）方面相似。我们发现，与地中海贫血患者或未接受输血的镰状细胞病患者相比，接受输血的镰状细胞病患者住院频率更高（P < 0.001）。在住院患者中，与地中海贫血患者（RR = 1.6，95% CI 1.0 - 2.5）或未接受输血的镰状细胞病患者（RR = 3.1，95% CI 1.3 - 7.3）相比，接受输血的镰状细胞病成年患者更有可能失业。通过血清铁蛋白评估的铁过载严重程度与住院频率之间存在正相关关系（r = ；P = 0.009）。在23.5±10个月的随访中报告了23例死亡（6例地中海贫血患者，17例接受输血的镰状细胞病患者）。在接受输血的镰状细胞病组中，与存活者相比，死亡者开始输血的时间更晚（25.3岁对12.4岁，P < 0.001），开始螯合治疗的时间也更晚（26.8岁对14.2岁，P = 0.01）。地中海贫血患者的未调整死亡率（2.2/100人年）低于接受输血的镰状细胞病患者（7.0/100人年；RR = 0.38：95% CI 0.12 - 0.99）。然而，考虑死亡年龄时未观察到差异。尽管治疗有所改善，但在这个当代接受输血的成年地中海贫血或镰状细胞病患者样本中，死亡率比美国普通人群高3倍。对这一独特队列的受试者进行长期随访将有助于进一步明确慢性、重度铁过载与发病和死亡之间的关系。
