University Children's Hospital Tübingen, Tübingen, Germany.
Department of Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
Transplant Cell Ther. 2022 Jul;28(7):355.e1-355.e9. doi: 10.1016/j.jtct.2022.03.027. Epub 2022 Apr 9.
Hematopoietic stem cell transplantation (HSCT) is associated with severe medical complications and variable outcomes depending on the recipient's disease stage and health condition. Biomarkers predicting outcome may have therapeutic relevance in pediatric cancer care. Insulin-like growth factor 1 (IGF-1), a mitogenic and anabolic peptide hormone expressed in almost all tissues, is the major growth factor in childhood. Decreased IGF-1 concentration in conditions that cause catabolic metabolism may reflect a patient's degree of physical robustness and serve as a predictive biomarker for transplantation outcome. We evaluated the impact of pretransplantation serum IGF-1 level on both survival and adverse events in 587 pediatric cancer patients who underwent autologous or allogeneic HSCT between 1987 and 2014 at the University Children's Hospital Tübingen. Survival probabilities of the entire cohort and of defined subgroups according to pretransplantation serum IGF-1 level were estimated using the Kaplan-Meier method. The mean pretransplantation IGF-1 level (n = 498) was low: -1.67 SDS (SD, 1.54). Completeness of follow-up was 96% at 3 years post-HSCT and 83% at 10 years. Overall survival (OS) at 10 years was 44.8% (95% confidence interval, 40.6% to 48.9%). Decreasing IGF-1 SDS was associated with significant increases in transplantation-related mortality (P = .027), sinusoidal obstruction syndrome (quartiles 4 to 1: 3%, 1%, 12%, and 12%; P < .001), and thrombotic microangiopathy (quartiles 4 to 1: 0%, 0%, 2%, and 5%; P = .004). Compared with patients in IGF-1 deciles 2 to 10, patients in IGF-1 decile 1 had significantly poorer outcome (P = .042) with lower median survival (12 months versus 68 months) and 10-year OS (37% versus 52%). This retrospective study suggests that pretransplantation serum IGF-1 level has utility as a predictor of survival and selected vascular adverse events that may have diagnostic and therapeutic relevance in pediatric cancer care.
造血干细胞移植（HSCT）会引起严重的医疗并发症，并根据受者的疾病阶段和健康状况而产生不同的结果。预测结果的生物标志物在儿科癌症治疗中可能具有治疗相关性。胰岛素样生长因子 1（IGF-1）是一种在几乎所有组织中表达的有丝分裂和合成代谢肽激素，是儿童时期的主要生长因子。在引起分解代谢的情况下，IGF-1 浓度降低可能反映了患者的身体健壮程度，并可作为移植结果的预测生物标志物。我们评估了 1987 年至 2014 年间在图宾根大学儿童医院接受自体或同种异体 HSCT 的 587 例儿科癌症患者的移植前血清 IGF-1 水平对生存和不良事件的影响。使用 Kaplan-Meier 法估计整个队列和根据移植前血清 IGF-1 水平定义的亚组的生存概率。移植前 IGF-1 水平（n=498）平均值较低：-1.67 SDS（SD，1.54）。HSCT 后 3 年和 10 年的随访完整率分别为 96%和 83%。10 年总生存率（OS）为 44.8%（95%置信区间，40.6%至 48.9%）。IGF-1 SDS 降低与移植相关死亡率显著增加相关（P=.027），窦状阻塞综合征（四分位数 4 到 1：3%、1%、12%和 12%；P<.001）和血栓性微血管病（四分位数 4 到 1：0%、0%、2%和 5%；P=.004）。与 IGF-1 十分位数 2 到 10 的患者相比，IGF-1 十分位数 1 的患者的预后明显较差（P=.042），中位生存时间（12 个月与 68 个月）和 10 年 OS（37%与 52%）较低。这项回顾性研究表明，移植前血清 IGF-1 水平可用作生存和选定血管不良事件的预测因子，这些不良事件在儿科癌症治疗中可能具有诊断和治疗相关性。
