Photo by Chad McNeeley
New research suggests hematopoietic stem cell transplant (HSCT) may increase the molecular age of peripheral blood T cells.
The study showed an increase in peripheral blood T-cell senescence in patients with hematologic malignancies who were treated with autologous (auto-) or allogeneic (allo-) HSCT.
The patients had elevated levels of p16INK4a, a known marker of cellular senescence.
Auto-HSCT in particular had a strong effect on p16INK4a, increasing the expression of this marker to a degree comparable to 30 years of chronological aging.
Researchers reported these findings in EBioMedicine.
“We know that transplant is life-prolonging, and, in many cases, it’s life-saving for many patients with blood cancers and other disorders,” said study author William Wood, MD, of the University of North Carolina School of Medicine in Chapel Hill.
“At the same time, we’re increasingly recognizing that survivors of transplant are at risk for long-term health problems, and so there is interest in determining what markers may exist to help predict risk for long-term health problems or even in helping choose which patients are best candidates for transplantation.”
With this in mind, Dr Wood and his colleagues looked at levels of p16INK4a in 63 patients who underwent auto- or allo-HSCT to treat myeloma, lymphoma, or leukemia. The researchers assessed p16INK4a expression in T cells before HSCT and 6 months after.
Among auto-HSCT recipients, there were no baseline characteristics associated with pre-transplant p16INK4a expression.
However, allo-HSCT recipients had significantly higher pre-transplant p16INK4a levels the more cycles of chemotherapy they received before transplant (P=0.003), if they had previously undergone auto-HSCT (P=0.01), and if they had been exposed to alkylating agents (P=0.01).
After transplant, allo-HSCT recipients had a 1.93-fold increase in p16INK4a expression (P=0.0004), and auto-HSCT recipients had a 3.05-fold increase (P=0.002).
The researchers said the measured change in p16INK4a from pre- to post-HSCT in allogeneic recipients likely underestimates the age-promoting effects of HSCT, given that the pre-HSCT levels were elevated in the recipients from prior therapeutic exposure.
The researchers also pointed out that this study does not show a clear connection between changes in p16INK4a levels and the actual function of peripheral blood T cells, but they did say that p16INK4a is “arguably one of the best in vivo markers of cellular senescence and is directly associated with age-related deterioration.”
So the results of this research suggest the forced bone marrow repopulation associated with HSCT accelerates the molecular aging of peripheral blood T cells.
“Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging,” said study author Norman Sharpless, MD, of the University of North Carolina School of Medicine.
“We know that, years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age.”
