Long-term Survival after Hematopoietic Cell Transplant for Sickle Cell Disease Compared to the United States Population.
Long-term Survival after Hematopoietic Cell Transplant for Sickle Cell Disease Compared to the United States Population.
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DOI：
10.1016/j.jtct.2022.03.014
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发表时间：
2022-06
影响因子：
3.2
通讯作者：
Eapen, Mary
中科院分区：
文献类型：
--
作者：
St Martin, Andrew;Hebert, Kyle M.;Serret-Larmande, Arnaud;Jouhet, Vianney;Hughes, Emily;Stedman, Jason;DeSain, Thomas;Pillion, Danielle;Lyons, Jessica C.;Steinert, Patricia;Avillach, Paul;Eapen, Mary
镰状细胞病的造血细胞移植是治愈性的，但与危及生命的并发症有关，其中大多数发生在移植后的前2年内。在当今对基因治疗和基因编辑感兴趣的时代，我们认为报告镰状细胞病移植受者在移植后至少存活2年的情况是及时的，这是以前没有报道过的。我们的目标是：1）报告移植后存活2年或更长时间的患者的条件生存率; 2）确定移植后2年以上死亡的风险因素; 3）将全因死亡风险与美国年龄、性别和种族匹配的一般人群进行比较。通过限制2年的存活率，我们排除了移植手术直接导致的死亡。从公开可用的数据源中审查了1149例患者的去识别记录，950例患者合格（https：picsure.biodatacatalyst.nhlbi.nih.gov）。所有分析均在该安全云环境中使用可用的统计软件包进行。公共数据库的有效性通过复制早期出版物的结果得到证实。使用Kaplan-Meier方法获得移植后存活给定时间长度（x）的子队列的条件生存估计值。建立考克斯回归模型以确定与移植后2年以上死亡率相关的危险因素。标准化相对死亡风险（SMR）或观察到的死亡人数与预期死亡人数的比率用于量化移植后的全因死亡风险，并与年龄、种族和性别匹配的一般人群进行比较。从锚日期（即，移植后2年、5年和7年）至死亡日期或已知最后存活日期。使用年龄、人种和性别特异性美国死亡率计算预期死亡人数。中位随访时间为5年（范围2 - 20年），300例（32%）患者观察时间超过7年。在移植后存活至少7年的患者中，12年生存率为97%（95%CI 92 - 99）。与年龄、种族和性别匹配的美国人群相比，移植后迟发性死亡的风险在移植后7年内更高（HR 3.2，p=0.020），但风险随着时间的推移而降低。晚期死亡的风险因素包括移植时的年龄和供体类型。患者年龄每增加10岁，老年患者死亡的可能性是年轻患者的1.75倍（p=0.0004）。与HLA匹配的同胞相比，使用其他供体与晚期死亡的风险较高相关（HR 3.49，p=0.003）。移植失败（移植后超过2年）为7%（95%CI 5 - 9），非HLA匹配同胞供体移植后移植失败率较高（HR 2.59，p<0.0001）。移植后的长期存活率非常好，并支持这种治疗方法作为镰状细胞病的治愈方法。预期的死亡风险随着时间的推移而降低，但晚期死亡的风险不可忽略。
Hematopoietic cell transplant for sickle cell disease is curative but is associated with life threatening complications most of which occur within the first 2 years after transplantation. In the current era with interest in gene therapy and gene editing we felt it timely to report on sickle cell disease transplant recipients who were alive for at least 2-year after transplantation, not previously reported. Our objectives were to 1) report the conditional survival rates of patients who were alive for 2 or more years after transplantation 2) identify risk factors for death beyond 2 years after transplantation and 3) compare all-cause mortality risks to those of an age-, sex- and race-matched general population in the United States. By limiting to 2-year survivors, we exclude deaths that occur as a direct consequence of the transplantation procedure. De-identified records of 1149 patients were reviewed from a publicly available data source and 950 patients were eligible (https://picsure.biodatacatalyst.nhlbi.nih.gov). All analyses were performed in this secure cloud environment using the available statistical software package(s). The validity of the public database was confirmed by reproducing results from an earlier publication. Conditional survival estimates were obtained using the Kaplan-Meier method for the sub-cohort that had survived a given length (x) of time after transplantation. Cox regression models were built to identify risk factors associated with mortality beyond 2 years after transplantation. The standardized relative mortality risk (SMR) or the ratio of observed to expected number of deaths, was used to quantify all-cause mortality risk after transplantation and compared to age, race and sex-matched general population. Person-years at risk were calculated from an anchor date (i.e., 2-, 5- and 7-years) after transplantation until date of death or last date known alive. The expected number of deaths was calculated using age, race and sex-specific US mortality rates. The median follow up was 5 years (range 2 – 20) and 300 (32%) patients were observed for more than 7 years. Among those who lived for at least 7 years after transplantation the 12-year probability of survival was 97% (95% CI 92 – 99). Compared to an age-, race- and sex-matched US population, the risk for late death after transplantation was higher as late as 7 years after transplantation (HR 3.2, p=0.020) but the risk receded over time. Risk factors for late death included age at transplant and donor type. For every 10-year increment in patient age, an older patient was 1.75 times more likely to die than a younger patient (p=0.0004). Compared to HLA-matched siblings the use of other donors was associated with higher risk for late death (HR 3.49, p=0.003). Graft failure (beyond 2-years after transplantation) was 7% (95% CI 5 – 9) and graft failure was higher after transplantation of grafts from donors who were not HLA-matched siblings (HR 2.59, p<0.0001). Long-term survival after transplantation is excellent and support this treatment as a cure for sickle cell disease. The expected risk for death recedes over time but the risk for late death is not negligible.
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DOI：
10.1016/s2352-3026(17)30104-7
发表时间：
2017-07
期刊：
The Lancet. Haematology
影响因子：
--
作者：
Eapen M;Wang T;Veys PA;Boelens JJ;St Martin A;Spellman S;Bonfim CS;Brady C;Cant AJ;Dalle JH;Davies SM;Freeman J;Hsu KC;Fleischhauer K;Kenzey C;Kurtzberg J;Michel G;Orchard PJ;Paviglianiti A;Rocha V;Veneris MR;Volt F;Wynn R;Lee SJ;Horowitz MM;Gluckman E;Ruggeri A
通讯作者：
Ruggeri A
影响因子：
24.7
作者：
Bolanos-Meade, Javier;Cooke, Kenneth R.;Brodsky, Robert A.
通讯作者：
Brodsky, Robert A.
影响因子：
4.3
作者：
de la Fuente, Josu;Dhedin, Nathalie;Kassim, Adetola A.
通讯作者：
Kassim, Adetola A.
影响因子：
10.1
作者：
Bernaudin, Francoise;Dalle, Jean-Hugues;Socie, Gerard
通讯作者：
Socie, Gerard
影响因子：
20.3
作者：
Horan, John;Wang, Tao;Woolfrey, Ann
通讯作者：
Woolfrey, Ann