Gerbek Tina, Thomsen Birthe Lykke, Muhic Ena, Christiansen Terkel, Sørensen Kaspar, Ifversen Marianne, Kofoed Klaus, Müller Klaus
Department of Pediatrics and Adolescent Medicine, University Hospital of Copenhagen, Copenhagen, Denmark.
Institute of Inflammation Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Pediatr Transplant. 2023 Jun;27(4):e14530. doi: 10.1111/petr.14530. Epub 2023 Apr 17.
Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies.
A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias.
Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high-grade TBI (8-12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0-4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00-0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (-59%, 95% CI: -71% to -42%).
The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria HDL and triglyceride.
代谢综合征（MetS）在儿童造血干细胞移植（HSCT）幸存者中很常见，但在长期随访研究中，幸存者和参与偏倚对危险因素的评估构成了挑战。
对1980年至2018年间接受移植的395名儿科患者组成的队列进行了调查。在2018年12月至2020年3月的随访中对MetS进行了评估。考虑了两个复合结局（（a）将MetS与死亡相结合，（b）将MetS、死亡和未参与相结合）以解决选择偏倚的风险。
在受邀参加随访的234名幸存者中，96人（中位年龄27岁）参与。参与者中MetS患病率为30%。唯一显著的HSCT危险因素是一个将HSCT指征和预处理与全身照射（TBI）相结合的变量（p = 0.0011）。与接受高剂量TBI（8 - 12 Gy）治疗的急性白血病（AL）相比，接受无/低剂量TBI（0 - 4.5 Gy）治疗的非恶性疾病的MetS患病率较低（OR = 0.04，95%置信区间（CI）：0.00 - 0.23）。对复合结局的分析表明，由于选择偏倚，高剂量TBI的影响被高估。仔细审查显示，AL患者中HSCT指征和高剂量TBI之间存在强烈的残余混杂。HSCT对MetS的影响反映了HSCT对高密度脂蛋白（HDL）和甘油三酯的影响。与接受高剂量TBI治疗的AL相比，接受无/低剂量TBI治疗的非恶性诊断患者的HDL更高（+40%，95% CI：+21%至+62%），甘油三酯更低（-59%，95% CI：-71%至-42%）。
由于选择偏倚和混杂，在随访研究中TBI对MetS的影响可能被高估。TBI的影响仅限于潜在可改变的MetS标准HDL和甘油三酯。
