Impact of Neurocognitive Dysfunction in a Veteran Population Undergoing First Outpatient Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Authors: Grant Shakira J. , Hannan Lindsay M. , Brand Jessica L. , Richard Robert E. , Wu Daniel Y. , Graf Solomon A. , Grim Jonathan , Burwick Nicholas , Chauncey Thomas R. 
Published: November 2019

INTRODUCTION
Older adults (age > 70 years) with multiple myeloma (MM) are at higher risk of early mortality partly due to age-related factors, including impairments of cognition and function. To date, few studies have investigated the prevalence of neurocognitive impairment prior to autologous hematopoietic stem cell transplantation (ASCT) and its impact on post-transplant outcomes.
We hypothesize, for patients with MM undergoing first outpatient ASCT, age >70 years or the presence of comorbid neurocognitive dysfunction decreases the time to first unplanned hospitalization occurring within 30 days post ASCT, and increases the overall length of stay (LOS) on the transplant service.
METHODS
We conducted a retrospective cohort study of 76 consecutive patients who underwent first ASCT at the Puget Sound Veterans Health Administration, for MM between January 2017 and December 2018. Patients with the following were excluded: amyloidosis, anaplastic plasmacytoma, and POEMS. Comprehensive psychological evaluations performed within 30 days prior to ASCT included: cognitive screening [Montreal Cognitive Assessment (MOCA)], depression [Patient Health Questionnaire-9 (PHQ-9)], and anxiety [General Anxiety Disorder- 7 (GAD-7)]. Functional status was assessed by activities of daily living (ADLS) and instrumental activities of daily living (IADLS). Data sources for table 1, included the institutional stem cell transplant database, and comprehensive electronic medical record review for each patient. This included vital status as of 7/15/19. Total LOS on the transplant service was measured as the time from arrival until discharge post-engraftment. For eligible patients, all portions of ASCT, including, stem cell collection, conditioning and stem cell infusion were completed as an outpatient. Statistical analyses were performed using SAS version 9.4. Kaplan Meier curves were generated to explore the association of cognitive scores and 1) time until first unplanned hospitalization within 30 days post-ASCT and 2) outpatient LOS on the stem cell transplant service.
RESULTS
Of the 76 patients undergoing ASCT, median age was 67 (range 40-79), 29% (22/76) were ≥ 70 years old . 67% (51/76) underwent ASCT within 1 year from diagnosis. The majority (73/76) scored ≥ 70 on a provider-assessed Karnofsky performance scale. Of those with MOCA scores available (n=64), impairments in cognition ranged from suspected mild cognitive impairment (MOCA 20-25) to probable cognitive impairment (MOCA 15-19), in 50% (32/64) and 6%( 8/64) of patients respectively. Those with MOCA scores< 26 were more likely to have ≥ 1 IADL impairment compared to those with scores ≥ 26 (Fisher Exact p=0.014). A total of 19 patients underwent planned hospitalization for conditioning followed by stem cell rescue, and therefore were not included in our analysis of unplanned hospitalization. Of the 57% (33/59) of patients with an unplanned inpatient admission within 30 days post-ASCT, the median time to first admission was 11 days. A total of 61% (17/28) and 53%(10/19) patients with MOCA <26 and ≥26, respectively, required hospitalization post-ASCT (log-rank p-value=0.70). There was no difference in the time to first unplanned hospitalization by age (<70, ≥70 years; log-rank p-value 0.58). Median time spent on the transplant service was 78 days (range 30 - 118). Suspected cognitive impairment did not influence time on the outpatient transplant service (median: 79 days MOCA <26 and 77 days MOCA ≥ 26, log-rank p-value=0.38). Median number of days on the transplant service differed by age group (log-rank p-value=0.02),) 76 vs 79 days in those age <70 and ≥70 respectively.
CONCLUSION
We found a high prevalence of cognitive impairment in MM patients undergoing first ASCT. However, we found no significant association between cognitive impairment or age and 30-day unplanned hospitalization. Older age (>70 years) was associated with a longer transplant service LOS. Thus, select older patients may have higher utilization of hospital resources post-ASCT compared to their younger counterparts. However confounding variables and selection bias may have influenced these preliminary results and additional analyses are ongoing. Future studies will evaluate the impact of age and pre-transplant neurocognitive function on additional outcomes, including longitudinal neurocognitive deterioration and impact on long-term morbidity and mortality.

Disclosures
Graf: TG Therapeutics: Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding.