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Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) as graft-versus-host disease (GvHD) prophylaxis post-hematopoietic cell transplantation (HCT) is safe and effective. Optimal serum levels of TAC in this combination remain undetermined. We hypothesized that TAC at initial steady state (TISS) of10 ng/mL could promote optimal transplant outcomes and prevent TAC-associated toxicities. We retrospectively analyzed a consecutive case series of 210 patients who received PTCy/TAC-based prophylaxis post-HCT from 1/2013-6/2018. Patients received HCT from haploidentical (n = 172) or mismatched donors (n = 38), and flat dose (FD) or weight-based dose (WBD) TAC. Twenty-four-month overall survival (OS), disease free survival (DFS), and relapse rate (RR) were 61%, 56%, and 22%, respectively, in TISS 10 ng/mL cohort (n = 176), and 50%, 43%, and 35%, respectively, in TISS ≥ 10 ng/mL cohort (n = 34) (OS, P = 0.71; DFS, P = 0.097; RR, P = 0.031). OS, DFS, RR, non-relapse mortality, acute GvHD grade II-IV, grade III-IV or chronic GvHD by TISS were similar in multivariable analysis. TISS ≥ 10 ng/mL conferred increased risk of viral infection (P = 0.003). More patients receiving FD vs. WBD had TISS 10 ng/mL (P = 0.001). Overall, TISS 10 ng/mL early post HCT conferred similar survival outcomes and lowered risk of viral infection and toxicities compared to TISS ≥ 10 ng/mL.

Hematopoietic cell transplantation is increasingly used in older adults with hematological malignancies. Younger adult patients who undergo HCT have shown to commonly present with cognitive impairment and depression prior to transplant; however, little research has been done to understand the cognitive and emotional functioning of older adults undergoing HCT. This study aimed to investigate the rate of cognitive impairment in a retrospective sample of older adult HCT candidates prior to transplant using a comprehensive battery. Ninety-three patients over the age of 60 completed a neuropsychology test battery that assessed standard domains of cognitive and emotional functioning. Impairment was defined as z-scores =-1.5 on at least two tests or a z score =-2.0 on at least one test. Results indicated that over 68% of patients were impaired with nearly a third of the sample showing impairment in verbal learning and memory and approximately one fifth showing impairments in aspects of executive function, processing speed, and visual learning. Ten percent of the patients endorsed symptoms indicative of a clinical level of depression. Medical comorbidities nor depression predicted cognitive impairment. These findings suggest that older adults candidates for HCT are at risk for cognitive impairment prior to transplant and thus cognition should be a consideration when developing treatment plans.