Telomere length and clonal chromosomal alterations in peripheral blood of patients with severe aplastic anaemia

Author:

Strauss, Joshua D [ORCID]

Brown, Derek W [ORCID]

Zhou, Weiyin [ORCID]

Dagnall,Casey [ORCID]

Yuan, Jian-Min [ORCID]

Im, Annie [ORCID]

Savage, Sharon A [ORCID]

Wang, Youjin [ORCID]

Rafati, Maryam [ORCID]

Spellman, Stephen R [ORCID]

Gadalla, Shahinaz M [ORCID]
Author Address

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., Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA., Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Center for International Blood and Marrow Transplant Research, NMDP, Minneapolis, Minnesota, USA.,

Abstract:

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.

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