Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation

SIMPLE SUMMARY: We studied cognitive (thinking) abilities and brain structure and function in older adults with multiple myeloma—a cancer of plasma cells—treated with high-dose chemotherapy and a stem cell transplant. The initial results suggested that after the chemotherapy and transplant, functional connectivity was diminished in regions involving the frontal and parietal lobes of the brain, while brain structure and cognitive function remained relatively stable. We also found increases in markers of inflammation after the transplant. The findings provide supporting evidence for the vulnerability of frontal and parietal brain regions to the side effects of chemotherapy. These preliminary findings would support the design of large future studies with the goal of developing therapeutic interventions. ABSTRACT: There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were significant decreases in RSFC post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022) and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029). There were no significant changes in GM or NF, except for improvements in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). In conclusion, RSFC decreased in frontal, parietal, and cingulate cortices post-HDC/ASCT, NF was relatively stable, and several PCy increased. These findings are congruent with other studies in cancer patients and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy’s adverse effects.