Reduced-Intensity Hematopoietic Stem Cell Transplant Spares Cognition


Key Points

  • Transplant recipients treated with full-intensity conditioning experienced cognitive decline, while those who received reduced-intensity conditioning had cognitive function post-transplant similar to that of healthy matched controls.
  • Shorter telomeres pretransplant were found to be associated with cognitive decline in female patients but not in males.

The intensity of transplant-related chemotherapy and radiation has effects on cognition, according to a study presented at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 913). Full-intensity hematopoietic stem cell transplant was associated with cognitive decline, while cognition remained intact in patients treated with reduced-intensity hematopoietic stem cell transplant. The study also found that cognitive decline was associated with shorter telomere length prior to transplant in females but not males.

“This study strongly indicates that patients who receive reduced-intensity transplants are generally spared from significant changes on their cognitive abilities, while full-intensity conditioning contributes to declines in multiple cognitive domains,” said study author Alysia Bosworth, of City Of Hope, Duarte, California. “As our results isolate a specific group of patients who would be considered ‘high-risk’ for cognitive impairment, including those who receive full-intensity transplants, it will be important for clinicians to evaluate and offer services to help these patients regain that function after transplant,” she added.

“We addressed the gaps in previous studies showing cognitive decline in transplant recipients. Unlike other studies, our study compared full- and reduced-intensity hematopoietic stem cell transplant and also included a healthy control comparison group,” said senior author Smita Bhatia, MD, of City of Hope, who presented the results at a press briefing.

Study Details

The prospective, longitudinal study assessed the trajectory of cognitive function in hematopoietic stem cell transplant recipients from pre–hematopoietic stem cell transplant (n = 242) to 2 years post–hematopoietic stem cell transplant using 14 standardized neurologic tests that assessed eight cognitive domains. Cognitive function was also assessed in 98 age- and gender-matched healthy controls at similar time points.

Median age of hematopoietic stem cell transplant recipients was 49 years and 51 years for healthy controls. The primary diagnosis was leukemia in 69%, lymphoma in 14%, and “others” in 17%. Full-intensity hematopoietic stem cell transplant conditioning was used in 116 patients (48%) and reduced-intensity conditioning in 126 patients (52%).

At 2 years post-transplant, 125 hematopoietic stem cell transplant patients and 45 healthy controls were evaluable.

Results showed that patients receiving full-intensity hematopoietic stem cell transplant exhibited declines in the following areas: executive function, processing speed, verbal speed, and visual memory, whereas those receiving reduced-intensity stem cell transplant exhibited no decline in these domains. In fact, those treated with reduced-intensity hematopoietic stem cell transplant had similar levels of cognitive function in all domains compared to healthy controls.

On multivariable, longitudinal analysis, in addition to full-intensity hematopoietic stem cell transplant, factors strongly associated with risk of cognitive decline included older age; male gender; Hispanic ethnicity; low education level, income, and cognitive reserve; and higher risk of relapse and high fatigue.

“These vulnerable subpopulations could benefit from multidisciplinary support,” Dr. Bhatia said.

Association With Telomere Length

The authors hypothesized that hematopoietic stem cell transplant recipients with shorter telomeres (which has been associated with Alzheimer’s disease) pretransplant would lead to reduced cognitive function after transplant. Telomere length was assessed in 142 patients prior to hematopoietic stem cell transplant. Women with shorter telomeres prior to transplant experienced cognitive decline, but this association did not hold true for males. Dr. Bhatia said that she and her colleagues have analyzed the data and still have no answer as to why this effect appears to be gender-specific.

The study authors reported no potential conflicts of interest.

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