Rodgers Nathan J, Kaizer Alexander M, Miller Weston P, Rudser Kyle D, Orchard Paul J, Braunlin Elizabeth A
Department of Pediatrics, Division of Pediatric Cardiology, Masonic Children's Hospital, University of Minnesota Medical School, Minneapolis, MN, 55454, USA.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
J Inherit Metab Dis. 2017 Mar;40(2):271-280. doi: 10.1007/s10545-016-0006-2. Epub 2017 Jan 4.
Mucopolysaccharidosis IH (MPS IH, Hurler syndrome) naturally leads to death within the first decade of life, primarily from cardiac and pulmonary causes. To determine how hematopoietic stem cell transplantation (HSCT) has altered mortality, we analyzed our institution's 30-year experience of patients with MPS IH undergoing HSCT.
Using chart review and the National Death Index, we determined survival status of 134 patients (males = 69) with MPS IH transplanted between 9/16/1983 and 7/25/2013 on 12/31/2013. Analysis included descriptive statistics, Kaplan-Meier curves, and regression analysis by Cox proportional hazards model.
Overall survival (95% CI) at one- and 25-years was 70% (62-78%) and 37% (19-55%), respectively. From 2004 onward, overall survival at one- and 8-years was 84% (73-96%) and 81% (69-94%), respectively, compared to 65% (55-74%) and 57% (47-67%) prior to 2004 (Log-rank p = 0.032). Regardless of era, male survival was significantly better than female (HR 0.40, [95% CI: 0.21-0.74], p = 0.004). The cumulative incidence of death (95% CI) at 25 years was 63% (45-81%); incidence of pulmonary-related death was the highest at 27% (10-41%) compared to 8% (0.3-16%) for cardiac, 12% (6-17%) for infectious disease, and 16% (3-27%) from other complications.
HSCT has increased survival in MPS IH beyond the third decade of life and decreased the incidence of cardiac mortality, but deaths after the third year post-HSCT occur in excess of expected US mortality. It is important to determine if improved transplant strategies since 2004 result in better long-term survival in the current patient population.
黏多糖贮积症Ⅰ型（MPS IH，Hurler综合征）通常会导致患者在生命的第一个十年内死亡，主要死因是心脏和肺部问题。为了确定造血干细胞移植（HSCT）如何改变死亡率，我们分析了本机构30年来对接受HSCT的MPS IH患者的治疗经验。
通过查阅病历和国家死亡指数，我们确定了1983年9月16日至2013年7月25日期间接受移植的134例MPS IH患者（男性69例）在2013年12月31日的生存状况。分析包括描述性统计、Kaplan-Meier曲线以及Cox比例风险模型的回归分析。
1年和25年的总生存率（95%置信区间）分别为70%（62-78%）和37%（19-55%）。从2004年起，1年和8年的总生存率分别为84%（73-96%）和81%（69-94%），而2004年之前分别为65%（55-74%）和57%（47-67%）（对数秩检验p = 0.032）。无论哪个时期，男性生存率均显著高于女性（风险比0.40，[95%置信区间：0.21-0.74]，p = 0.004）。25年时的累积死亡发生率（95%置信区间）为63%（45-81%）；肺部相关死亡发生率最高，为27%（10-41%），而心脏相关死亡为8%（0.3-16%），传染病相关死亡为12%（6-17%），其他并发症相关死亡为16%（3-27%）。
HSCT提高了MPS IH患者超过第三个十年的生存率，并降低了心脏死亡率，但HSCT后第三年之后的死亡发生率超过了美国预期死亡率。确定2004年以来改进的移植策略是否能使当前患者群体获得更好的长期生存很重要。
