Study Finds Hematopoietic Cell Transplants May Age Immune Cells

A study funded by the National Institutes of Health found that certain blood cancer treatments may lead to the premature aging of immune cells.

Researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center tracked a molecular marker that has been shown to increase in white blood cells as people age and found that hematopoietic cell transplantation (HCT) is linked to a marked increase in the “molecular age” of these immune cells in a group of patients with blood cancer.

The results, published in EBioMedicine, indicate that patients who have undergone autologous HCT (AHCT) had elevated levels of expression of messenger RNA – comparable to those found in an individual who is 30 years older in chronologic age.

“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 the study’s lead author William Wood, MD, associate professor in the Division of Hematology and Oncology at UNC School of Medicine. “At the same time, we’re increasingly recognizing that survivors of transplant are at risk for long-term health problems, 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.”

The authors then examined p16 protein levels, which is associated with an exponential increase with chronologic age, in 63 patients with myeloma, lymphoma, or leukemia who had undergone AHCT and allogeneic HCT (alloHCT) at UNC hospitals.

While they found a higher expression of mRNA coding for p16 in the T cells of patients who underwent alloHCT and AHCT, patients receiving AHCT had a larger increase, one that was three times higher than pre-transplant levels. AHCT also had the strongest effect on molecular aging of T cells – even greater than the effect of cytotoxic chemotherapy.

The authors speculated that the forced regeneration of bone marrow that accompanies re-engraftment may contribute to stem cell aging from AHCT. Chemotherapy prior to transplant may also contribute to increased p16 mRNA expression, which could doubly impact patients.

The expression of this marker is “arguably one of the best in vivo marker of cellular senescence and is directly associated with age-related deterioration,” the authors noted.

Sources: UNC press release, September 1, 2016; Wood WA, Krishnamurthy J, Nitin N, et al. Chemotherapy and stem cell transplantation increase p16INK4a expression, a biomarker of T-cell aging. EBioMedicine. 2016 August 21. [Epub ahead of print]

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