Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, France.
Blood. 2012 Oct 18;120(16):3353-9. doi: 10.1182/blood-2012-01-403337. Epub 2012 Sep 4.
Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.
端粒磨损诱导细胞衰老和凋亡。我们假设，经过年龄调整的移植前端粒长度可能预测造血干细胞移植（HSCT）后的治疗相关死亡率（TRM）。在 2000 年至 2005 年间，178 例连续患者接受了 HLA 匹配的同胞供体 HSCT，预处理方案为清髓性，主要用于血液系统恶性肿瘤（n = 153）。在 HSCT 前通过实时定量 PCR 测量血液淋巴细胞的端粒长度。分析移植前经年龄调整的端粒长度与临床结果的相关性。经过年龄调整后，患者的端粒长度分布在所有 4 个四分位数中除疾病阶段外相似。端粒长度与植入、GVHD 或复发均无相关性。5 年总生存率为 62%（95%置信区间[CI]，54-70）。中位随访 51 个月（范围，1-121 个月）后，43 例患者因 TRM 死亡。TRM 率与端粒长度呈反比。第一（端粒长度最低）四分位的患者的 TRM 率明显高于端粒较长的患者（P =.017）。多变量分析显示，受者年龄（风险比，1.1；95%CI，.0-1.1；P =.0001）和经年龄调整的端粒长度（风险比，0.4；95%CI；0.2-0.8；P =.01）与 TRM 独立相关。总之，经过年龄调整的受者端粒长度是 HSCT 后 TRM 的独立生物学标志物。
