Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT

Abstract

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

Use of geriatric assessment in hematopoietic cell transplant

“…Cognition is an important consideration when evaluating older adults for HCT. The prevalence of cognitive impairment in pre-transplant patients is highly variable, reported at 5-47% of patients with deficits in one of 8 domains (attention/concentration, perceptual processing, learning working memory, executive function, language, processing speed, motor function, emotion) [69]. Independent of age, allogeneic HCT survivors have more neurocognitive dysfunction than healthy controls, at rates of over 30-35% compared to 9-20% [70,71].…”

“…Methods to reduced neurocognitive decline include minimizing cranial radiation, total body irradiation (TBI), or substitution of busulfan for TBI-based conditioning regimens. There is evidence to suggest exercise improves neurocognitive function in patients with cancer; further studies may be useful in HCT recipients [69].…”

Long‐term Follow‐up of Hematopoietic Stem Cell Transplant Survivors: A Focus on Screening, Monitoring, and Therapeutics

“…15 Neurocognitive dysfunction has been documented at 22 to 82 months post-HCT in~60% of patients. 15,31,32 Pretransplant chemotherapy, use of total body irradiation (TBI) in conditioning, immunosuppressive therapies, length of hospital stay, and GVHD are some of the risk factors that increase the risk of neurocognitive dysfunction. Potential interventions to decrease the risk of neurocognitive dysfunction in HCT survivors include: (i) reducing the use of neurotoxic therapies (i.e., prophylactic cranial radiation, TBI, or neurotoxic agents) during treatment, (ii) prompt identification and management of acute central nervous system toxicities after HCT (i.e., posterior reversible encephalopathy syndrome), (iii) non-pharmacological interventions (i.e., job training, cognitive remediation and rehabilitation, computer or web-based cognitive training, stress management, and exercise), and (iv) pharmacologic interventions with stimulants, donepezil, or recombinant growth hormone.…”

Maintenance Strategies After Hematopoietic Cell Transplantation

“…The initial success with rituximab opened the door to other immunotherapies, including the recognition that PD-1 expression is present in DLBCL tumors, albeit to a lesser extent than FL. 47 A multicenter phase II trial evaluated the administration of 3 doses of anti-PD-1 monoclonal antibody, pidilizumab, after auto-HCT. 48,49 Of the 66 treated patients, 72% met the primary endpoint of 16 month PFS, and 70% of high-risk patients with PET positivity prior to auto-HCT met this endpoint.…”