Use of Pre-Transplant Minicog Cognitive Impairment Screening and Validation of Frailty and Functionality Assessment Prior to Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Alfaro Tommy , Salas Maria Queralt , Atenafu Eshetu , Bascom Ora , Wilson Leeann , Chen Carol , Law Arjun D. , Gerbitz Armin , Viswabandya Auro , Michelis Fotios , Lipton Jeffrey H. , Lam Wilson , Novitzky-Basso Igor , Kim Dennis (Dong Hwan) Dong Hwan , Mattsson Jonas , Pasic Ivan , Kumar Rajat 
Published: December 2023

Background: We demonstrated that impaired functionality and frailty have a negative impact on survival after allogeneic hematopoietic cell transplantation (HCT) (Salas et al., 2019). This impact is independent of other predictive models including HCT comorbidity index (HCT-CI) and disease risk index (DRI). Cognitive changes are frequently reported among survivors of autologous and allogeneic HCT. However, impact of the presence of cognitive impairment prior to allogeneic HCT has not been studied. We hypothesized that the presence of cognitive impairment before transplantation could have a negative effect on the outcomes of allogeneic HCT.

Patients and methods: We evaluated transplant outcomes of 277 patients who underwent our updated frailty assessment including the MiniCog scale, incorporated as standard of care in April 2020. The MiniCog assessment included recalling of three unrelated words, for a total of three points and drawing of a clock with the face, number and hands indicating a specific time, for a total of 2 points. We used the cutoff score of &lt;3 as a marker of cognitive impairment and evaluated the effect of cognitive impairment on: overall survival (OS), relapse free survival (RFS), non-relapse mortality (NRM). We further sought to validate our previously described frailty scale in prediction of transplant outcomes, including OS, RFS, and NRM, in the new cohort and compare its performance in outcome prediction to the MiniCog scale. Our frailty evaluation included the following variables: Clinical Frailty Scale (CFS), Lawton's instrumental activities of daily living (IADL), timed to get up and go test (TUGT), grip strength (GS) using a hydraulic hand dynamometer, self-rated health questionnaire (SRH), a question on number of falls in the last year (F), C-reactive protein (CRP) and serum albumin (Alb) levels at the time of the consult. The frailty scale was calculated according to the following formula: 1.5×CFS + 1×IADL +1×GS + 1.5×TUGT +1×SRH+1×F+ 1.5×Alb+2×CRP. The frailty scale score ranged from 0-10.5. With these results we stablished 3 frailty cohorts for the patients being planned for alloHCT, fit (≤1), pre-frail (&lt;1 to ≤5.5), and frail (&gt;5.5), based on this risk model.

Results: Median age at transplantation was 59 years and 85 (31%) patients were ≥ 65 years. Of all the patients, 36 (14%) had a Karnofsky Performance Scale Index (KPS) of &lt;90%, 206 patients had a low-intermediate risk disease risk index (DRI). Median time of follow up was 9 months. Majority of the patients (46%) underwent transplantation for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Of all patients, 246 (88.8%) had a normal MiniCog score (&gt;3). There was no difference in 2-y OS between patients with normal and low MiniCog score: 67% (95% confidence interval (CI): 59%-74%) vs 60% (95% CI: 36-78%), p=0.21. NRM at 24 months was 26% (95% CI 10-46%) for patients with an abnormal MiniCog vs 23% (95% CI 17-30%), p=0.80. There was no difference in 2-year RFS between patients with normal and low MiniCog score: 65% (95% CI 57-72%) vs 43.5% (95% CI 23-63%), p=0.09. Using the frailty scale, 144 (56%) patients were considered fit, 30 (12%) pre-frail and 81 (32%) frail. Using our original frailty scale, the 2-y OS among the fit, pre-frail and frail patients was: 78% (95% CI 65%-87%), 64% (95% CI 53%-74%) and 27% (95% CI 5.6%-55.6%) p=0.005. 2-year NRM was 19.2% (95% CI 9-31%), 23% (16-32%), and 41.6% (95% CI 11-70%) for the fit, pre-frail and frail patients respectively, p=0.12. Relapse free survival at 24 months was 72.5% (95% CI 58-83%), 60.5% (95% CI 50-70%), and 29% (95% CI 6-57%), p=0.003.

Conclusions: In our cohort the sole presence of cognitive decline, based on the MiniCog assessment failed to be a predictor of outcomes after allogeneic HCT. However, ability of our preciously established frailty scale to predict transplant outcomes in this new cohort of patients further validates the results of our previous findings. The presence of frailty is an independent predictor of adverse outcomes after allogeneic HCT.