CT-162: Ageing of Long-term Allogeneic Hematopoietic Cell Recipients Compared to Their Donors

Abstract

Context Although allogeneic hematopoietic cells transplantation (allo-HCT) is a well-established, curative option in a variety of hematologic malignancies, its influence on ageing remains poorly understood. Therefore, we launched a comprehensive study, aiming at assessing age-related changes in allo-HCT long-term survivors, compared to their donors. Objective To investigate ageing-associated changes in main lymphocyte subpopulations (CD4, CD8, CD19, CD56), by assessing telomeric shortening and abnormalities in immunophenotype. We hypothesize, that allo-HCT survivors experience, as healthy elderly, telomeric shortening, premature immunosenescence, and inflammaging, caused by clonal expansion required for rebuilding of hematopoiesis. Design Planned duration of the project: August 2019 to August 2020. Material: venous blood. All participants' PBMCs samples undergo telomeric length measurement (qPCR) and immunophenotype assessment. The results will be tested for any correlation with ageing-associated morphological features (such as Klotho protein and calpaincalpastatin system). Patients Population: 20 recipient-donor pairs. To date, we have examined 9 out of 20 scheduled pairs. Allo-HCT recipients had undergone the engraftment due to a variety of hematological malignancies (i.e., AML, ALL, CML, PNH). Median current age of participants — 51.5 years (11 males, 7 females). Enrolled patients are at least 10 years after allo-HCT with intrinsic control of living donors. Main outcome measures The preliminary results suggest an existence of differences in telomeric length between recipients and donors in all lymphocyte subpopulations (2 pairs examined). Results Telomeric length measurement in 2 recipient (R) - donor (D) pairs (average length per chromosome): TCD4+ (R – 11kb, D – 2kb), TCD8+ (R – 8.5kb, D – 6.5kb), CD19+ (R – 9kb, D – 13kb), CD 56+ (R – 4.5kb, D - 9.5kb). Immunophenotype analysis of 9 R-D pairs has shown no statistically significant (p Conclusions The data suggest the differences in telomeric length in all lymphocyte subpopulations tested. We have not found, as yet, any statistically significant differences in immunophenotype. Observed increase in the percentage of NKT-like subpopulation in allo-HTC recipients, similar to that observed in individuals with autoimmune disorders, though interesting, requires further studies. National Science Center, Poland grants: PRELUDIUM (2018/31/N/NZ3/01035), MINIATURA (2019/03/X/NZ3/01848).