Comparison of telomere length in patients with bone marrow failure syndromes and healthy controls.

INTRODUCTION: During normal aging, telomeric DNA is gradually lost in dividing somatic cells, and critically short telomeres lead to replicative senescence, apoptosis, or chromosomal instability. We studied telomere length in bone marrow failure syndromes (BMFS) compared to normal healthy population. METHODS: Peripheral blood was collected from the participants, and genomic DNA was extracted. Relative telomere length was measured using a quantitative polymerase chain reaction. Statistical analysis was performed using SPSS and GraphPad Prism 8.2 software. RESULTS: The median age of normal Indian population was 31 (0-60) years. As expected, telomere length (TL) showed a decline with age and no difference in TL between males and females. The median age of 650 patients with aplastic anemia (AA) was 30 (1-60) years. TL was significantly shorter in patients with AA compared to healthy controls (p < .001). In FA and MDS patients, TL was significantly shorter than age-matched healthy controls (p = .028; p < .001), respectively. There was no difference between the median TL in age-matched AA and FA patients (p = .727). However, patients with MDS had shorter TL than age-matched AA (p = .031). CONCLUSION: TL in BMF syndrome patients was significantly shorter than age-matched healthy controls.

Impact of donor telomere length on survival in patients undergoing matched sibling donor transplantation for aplastic anaemia.

Although telomere shortening is seen frequently in patients with aplastic anaemia (AA), there are no data on its association in matched sibling donor (MSD) transplants. We evaluated the effect of pre-transplant telomere length of patients and donors, measured by quantitative real-time polymerase chain reaction in 163 recipients undergoing MSD transplants. The median age of patients and donors was 24 and 26 years, respectively. Fludarabine and cyclophosphamide was the main conditioning regimen used and all received peripheral blood stem cell grafts. Engraftment occurred in 89% with graft failure (primary and secondary) in 6%. Acute and chronic graft-versus-host disease (GVHD) occurred in 28% and 24%, respectively. At a median follow-up of 37 months, 117 patients (72%) were alive. All patients and donors were divided into short and long telomere length based on their median and quartile values. Patient telomere length was not associated with severity of AA, neutrophil recovery, graft failure, acute GVHD or chronic GVHD. Longer donor telomere length was associated with better overall survival [hazard ratio (HR) = 0·2, P = 0·006] but did not influence neutrophil recovery, graft failure, acute or chronic GVHD. The five-year overall survival was significantly better (94·9 ± 3·5% vs 65·4 ± 4·3%, P = 0·002) for donors with long (highest quartile, DTL-HQ) versus short (lower three quartiles, DTL-LQ) telomeres, respectively. On multivariate analysis, longer donor telomere length, recipient age and acute GVHD continued to remain significant. This is the first study demonstrating an association of donor telomere length on overall survival following MSD transplant for AA but it needs to be confirmed in larger studies.