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Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 10 9 /L (range, 0.01-2.75 × 10 9 /L) and was significantly higher in patients who achieved complete response (p = 0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2-0.8, p = 0.007). Low DLIx was independently associated with shorter progression-free (p = 0.02) and overall survival (p = 0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To cross-sectionally study subjective memory complaints (SMC) in autosomal dominant Alzheimer disease (ADAD)., Methods: We examined self-reported and study partner-based SMC in 52 young, cognitively unimpaired individuals from a Colombian kindred with early-onset ADAD. Twenty-six carried the PSEN-1 E280A mutation, averaging 7 years of age younger than the kindred's expected clinical onset. Twenty-six were age-matched noncarriers. Participants also underwent structural MRI and cognitive testing., Results: Self-reported SMC were greater in carriers than noncarriers ( p = 0.02). Study partner-based SMC did not differ between groups ( p = 0.21), but in carriers increased with age ( r = 0.66, p < 0.001) and decreased with hippocampal volume ( r = -0.35, p = 0.08)., Conclusions: Cognitively unimpaired PSEN-1 carriers have elevated SMC. Self-reported SMC may be a relatively early indicator of preclinical AD, while partner- reported SMC increases later in preclinical AD, closer to clinical onset., (© 2017 American Academy of Neurology.)