Chow Eric J, Wong Kenneth, Lee Stephanie J, Cushing-Haugen Kara L, Flowers Mary E D, Friedman Debra L, Leisenring Wendy M, Martin Paul J, Mueller Beth A, Baker K Scott
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington.
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California.
Biol Blood Marrow Transplant. 2014 Jun;20(6):794-800. doi: 10.1016/j.bbmt.2014.02.012. Epub 2014 Feb 22.
The authors sought to better understand the combined effects of pretransplant, transplant, and post-transplant factors in determining risks of serious cardiovascular disease after hematopoietic cell transplantation (HCT). Hospitalizations and deaths associated with serious cardiovascular outcomes were identified among 1379 Washington State residents who received HCT (57% allogeneic and 43% autologous) at a single center from 1985 to 2005, survived ≥ 2 years, and followed through 2008. Using a nested case-cohort design, relationships (hazard ratios [HRs]) between potential risk factors and outcomes were examined among affected survivors and a randomly selected subcohort (N = 509). After 7.0 years of median follow-up (range, 2.0 to 23.7), the 10-year cumulative incidence of ischemic heart disease, cardiomyopathy, stroke, and all-cause cardiovascular death was 3.8%, 6.0%, 3.5%, and 3.7%, respectively. In multivariable analysis, increased pretransplant anthracycline was associated with cardiomyopathy. Active chronic graft-versus-host disease was associated with cardiovascular death (HR, 4.0; 95% confidence interval, 1.1 to 14.7); risk was otherwise similar between autologous versus allogeneic HCT recipients. Independent of therapeutic exposures, pretransplant smoking, hypertension, dyslipidemia, diabetes, and obesity conferred additional risk of all outcomes except stroke (HR ≥ 1.5 for each additional risk factor, P < .03). Hypertension and dyslipidemia at 1 year with persistence of these conditions 2 or more years after HCT also were associated with independent risks of multiple outcomes. HCT survivors with preexisting or newly developed and persistent cardiovascular risk factors remain at greater risk of subsequent serious cardiovascular disease compared with other survivors, independent of chemo- and radiotherapy exposures. These survivors should receive appropriate follow-up and be considered for primary intervention.
作者试图更好地了解移植前、移植过程中和移植后因素对造血细胞移植(HCT)后严重心血管疾病风险的综合影响。在1985年至2005年于单一中心接受HCT(57%为同种异体移植,43%为自体移植)、存活≥2年并随访至2008年的1379名华盛顿州居民中,确定了与严重心血管结局相关的住院和死亡情况。采用巢式病例队列设计,在受影响的幸存者和随机选择的子队列(N = 509)中检查潜在风险因素与结局之间的关系(风险比[HRs])。中位随访7.0年(范围2.0至23.7年)后,缺血性心脏病、心肌病、中风和全因心血管死亡的10年累积发病率分别为3.8%、6.0%、3.5%和3.7%。在多变量分析中,移植前蒽环类药物使用增加与心肌病相关。活动性慢性移植物抗宿主病与心血管死亡相关(HR,4.0;95%置信区间,1.1至14.7);自体与同种异体HCT受者之间的风险在其他方面相似。与治疗暴露无关,移植前吸烟、高血压、血脂异常、糖尿病和肥胖会增加除中风外所有结局的风险(每个额外风险因素的HR≥1.5,P <.03)。移植后1年出现高血压和血脂异常且这些情况持续2年或更长时间也与多种结局的独立风险相关。与其他幸存者相比,有既往或新出现且持续存在心血管危险因素的HCT幸存者后续发生严重心血管疾病的风险仍然更高,与化疗和放疗暴露无关。这些幸存者应接受适当的随访,并考虑进行一级干预。