Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Br J Haematol. 2024 Sep;205(3):1180-1187. doi: 10.1111/bjh.19681. Epub 2024 Aug 5.
Severe aplastic anaemia (SAA) is a rare and life-threatening bone marrow failure disorder. We used data from the transplant outcomes in aplastic anaemia study to characterize mosaic chromosomal alterations (mCAs) in the peripheral blood of 738 patients with acquired SAA and evaluate their associations with telomere length (TL) and survival post-haematopoietic cell transplant (HCT). The median age at HCT was 20.4 years (range = 0.2-77.4). Patients with SAA had shorter TL than expected for their age (median TL percentile for age: 35.7th; range <1-99.99). mCAs were detected in 211 patients (28.6%), with chr6p copy-neutral loss of heterozygosity (6p-CNLOH) in 15.9% and chr7 loss in 3.0% of the patients; chrX loss was detected in 4.1% of female patients. Negative correlations between mCA cell fraction and measured TL (r = -0.14, p = 0.0002), and possibly genetically predicted TL (r = -0.07, p = 0.06) were noted. The post-HCT 3-year survival probability was low in patients with chr7 loss (39% vs. 72% in patients with chr6-CNLOH, 60% in patients with other mCAs and 70% in patients with no mCAs; p-log rank = 0.001). In multivariable analysis, short TL (p = 0.01), but not chr7 loss (p = 0.29), was associated with worse post-HCT survival. TL may guide clinical decisions in patients with SAA.
严重再生障碍性贫血（SAA）是一种罕见且危及生命的骨髓衰竭性疾病。我们利用再生障碍性贫血移植研究的移植结果数据，对 738 例获得性 SAA 患者外周血中的嵌合体染色体改变（mCA）进行了特征描述，并评估了它们与端粒长度（TL）和造血细胞移植（HCT）后生存的关系。HCT 时的中位年龄为 20.4 岁（范围=0.2-77.4）。SAA 患者的 TL 比预期年龄短（年龄的 TL 中位数百分位数：第 35.7 百分位数；范围<1-99.99）。211 例患者（28.6%）检测到 mCA，其中 15.9%的患者存在 6p 染色体杂合性丢失（6p-CNLOH），3.0%的患者存在 7 号染色体缺失；4.1%的女性患者检测到 X 染色体缺失。mCA 细胞分数与测量 TL 呈负相关（r=-0.14，p=0.0002），可能与遗传预测 TL 呈负相关（r=-0.07，p=0.06）。7 号染色体缺失患者的 HCT 后 3 年生存率较低（39%vs.6p-CNLOH 患者 72%，其他 mCA 患者 60%，无 mCA 患者 70%；p-log 秩=0.001）。多变量分析显示，短 TL（p=0.01）而不是 7 号染色体缺失（p=0.29）与 HCT 后生存不良相关。TL 可能指导 SAA 患者的临床决策。
