Pilot Randomized Controlled Trial of an Educational Video for CAR T-Cell Therapy Recipients.

BACKGROUND: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but it is complex and challenging to convey to patients. Educational video interventions are efficacious for improving patient knowledge about cancer therapeutics and informing their care preferences, yet no educational videos have been evaluated in CAR T-cell therapy. METHODS: We conducted a randomized controlled trial comparing an educational video versus usual care in adults (age ≥18 years) with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital. Intervention participants watched a 13-minute video depicting how CAR T-cell therapy works, logistics, toxicities, prognosis, recovery, and approaches for dealing with prognostic uncertainty. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability (≥80% reporting comfort with the video), patients' knowledge about CAR T-cell therapy (10-item test), and self-efficacy (Communication and Attitudinal Self-Efficacy Scale-Cancer), decision satisfaction (Decision Conflict Scale), psychological distress (Hospital Anxiety and Depression Scale), and preference for CAR T-cell therapy. RESULTS: We enrolled 79% (80/101) of eligible patients. Of that group, 91% (30/33) reported being very or somewhat comfortable watching the video, and 94% (31/33) would definitely or probably recommend the video. At 1 month, participants in the video arm reported higher self-efficacy (mean difference [MD], 9.2 [95% CI, -4.0 to 22.3]; Cohen's d, 0.32), decision satisfaction (MD, 2.5 [95% CI, 0.7-4.2]; Cohen's d, 0.67), and lower anxiety (MD, -0.8 [95% CI, -2.5 to 0.7]; Cohen's d, 0.26) compared with participants in the usual care arm. At 1 week, both arms reported high preferences for CAR T-cell therapy (video arm, 94% [33/35]; usual care, 84% [27/32]). CONCLUSIONS: We found that an educational video for patients receiving CAR T-cell therapy was feasible and acceptable. The educational video demonstrated promising preliminary effects on patient self-efficacy and decision satisfaction and warrants further study.

Clinical Outcomes and Toxicity in Older Adults Receiving Chimeric Antigen Receptor T Cell Therapy.

Chimeric antigen receptor T cell therapy (CAR-T) has transformed the treatment landscape for adults with relapsed/refractory hematologic malignancies, but few studies have examined outcomes in older adults. We aimed to evaluate clinical outcomes and treatment toxicity in older adults receiving CAR-T for hematologic malignancies and to describe outcomes and toxicities in older adults age 75+ years compared to those age 65 to 74 years. We conducted a retrospective analysis of 141 adult patients age 65+ years (46.1% age 75+ years) who received commercial CAR-T at Massachusetts General Hospital between December 2017 and June 2023. We abstracted clinical outcomes from a review of the electronic health record, including (1) toxicity (ie, cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]); (2) health care utilization; (3) overall survival (OS); and (4) event-free survival (EFS). We analyzed the association of age (65 to 74 years versus 75+ years) with toxicity and health care utilization using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. We examined the association of age with OS and EFS using multivariable Cox regression, controlling for covariates. The median patient age was 77 years (range, 75 to 91 years) in the 75+ year group and 69 years (ranges, 65 to 74 years) in the 65 to 74 year group. There were no statistically significant differences between the 75+ year group and the 65 to 74 year group in the rates of CRS (75.4% versus 84.2%; P = .21), grade 3+ CRS (1.5% versus 6.6%; P = .24), ICANS (38.5% versus 48.7%; P = .24), grade 3+ ICANS (16.9% versus 21.1%; P = .49), or infections (23.1% versus 29.0%; P = .45). There were no significant between-group differences in hospital readmissions within 30 days of CAR-T (10.8% versus 21.1%; P = .11), intensive care unit admissions within 30 days of CAR-T (7.7% versus 9.2%; P = 1.000), or median hospital length of stay (13 days versus 14 days; P = .29) among age groups. In a multivariable Cox regression analysis controlling for CAR-T product, Eastern Cooperative Oncology Group Performance Status, lactate dehydrogenase level, bridging therapy use, and history of deep venous thromboembolism, age 75+ years was not associated with OS (hazard ratio [HR], .95; P = .86) or EFS (HR, 1.28; P = .30). We identified favorable OS and toxicity outcomes across age categories in older adults receiving CAR-T for B cell non-Hodgkin lymphoma or multiple myeloma, underscoring that age alone is not a contraindication for CAR-T.

Quality of Life and Prognostic Awareness in Caregivers of Patients Receiving Chimeric Antigen Receptor T Cell Therapy.

Caregivers of patients undergoing chimeric antigen receptor T cell therapy (CAR-T) play a critical role during treatment, yet their experience remains largely unaddressed. We aimed to longitudinally describe quality of life (QoL) and psychological distress, as well as prognostic awareness, in caregivers and explore the association of prognosis awareness with baseline psychological distress. We conducted a longitudinal study of caregivers of patients undergoing CAR-T and examined QoL (CAReGiverOncology QoL questionnaire) and psychological distress (Hospital Anxiety and Depression Scale) prior to CAR-T (baseline) and at days 7, 30, 90, and 180 post-CAR-T. At baseline, caregivers and patients completed the Prognostic Awareness Impact Scale, which examines cognitive understanding of prognosis, emotional coping with prognosis, and adaptive response (ie, capacity to use prognostic awareness to inform life decisions). We enrolled 58% (69 of 120) of eligible caregivers. Caregivers reported QoL impairments that did not change over time (B = 0.09; P = .452). The rates of clinically significant depression and anxiety symptoms were 47.7% and 20.0%, respectively, at baseline, and 39.1% and 17.4% at 180 days. One-third (32%) of the caregivers and patients reported that their oncologist said the cancer is curable. Caregivers' greater emotional coping with prognosis was associated with fewer symptoms of anxiety (B = -.17; P < .001) and depression (B = -.02; P < .001). Cognitive understanding of prognosis and adaptive response were not associated with psychological distress. Caregivers reported QoL impairments throughout the study period. A substantial proportion of caregivers experienced psychological distress and reported misperceptions about the prognosis, highlighting the need for supportive care interventions.

Communication About Chimeric Antigen Receptor T-Cell (CAR-T) Therapy.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of patients with hematologic malignancies, yet treatment may coincide with the potential for life-threatening toxicities. Currently, no studies have investigated how oncologists communicate with patients about CAR-T therapy or what patients and their caregivers want to know prior to consenting for CAR-T therapy. This study characterizes the content of oncologist communication with patients and caregivers about the risks and benefits of CAR-T therapy and explore the information preferences of patients and their caregivers about CAR-T therapy. We conducted a multimethod study of 20 patients with hematologic malignancies referred for CAR-T therapy at the Massachusetts General Hospital and 10 caregivers. We audio recorded the initial outpatient visit with the oncologist to review and sign consent for CAR-T therapy. We subsequently surveyed patients and caregivers about information gaps that remained after consent. We then interviewed patients and caregiver about their perceptions of oncologist communication and information preferences after the consent visit, 1 month, and 3 months post-CAR-T therapy treatment. Qualitative data analysis was conducted using the framework approach. Six major themes regarding communication about CAR-T therapy were identified: (1) oncologists create a narrative of power and innovation about CAR-T therapy, (2) oncologists set clear expectations regarding CAR-T therapy, (3) oncologists preferentially discuss positive treatment outcomes and less frequently address treatment failures or uncertainties, (4) oncologists couple their discussion about risks of CAR-T therapy with assurances about risk mitigation strategies, (5) oncologists engage in empathetic communication throughout the consent visit, (6) patients and caregivers vary in their preferences regarding communication about CAR-T therapy but largely favor a positive discourse during the consent visit and (7) patients who completed CAR-T therapy and their caregivers report significant knowledge gaps during and after treatment. Overall, patients and caregivers felt well informed about CAR T-therapy yet identified communication gaps regarding, advanced care planning, treatment failure and treatment toxicities. A predominantly positive discourse between patients, caregivers, and oncologists around CAR-T therapy leaves patients and caregivers with significant knowledge gaps about negative outcomes. Further research is needed to help oncologists communicate about treatment uncertainties and help patients and their caregivers prepare for negative outcomes of CAR-T therapy.

KLRG1 Cell Depletion As A Novel Therapeutic Strategy In Patients With Mature T-cell lymphoma Subtypes.

PURPOSE: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms. EXPERIMENTAL DESIGN: Primary specimens, cell lines, patient-derived xenograft models, commercially available and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation. RESULTS: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL) and gamma/delta T-cell lymphoma (G/D TCL). The majority of the CD8+/CD57+ or CD3-/CD56+ leukemic cells derived from patients with T- and NK-large granular lymphocytic leukemia (T-LGLL and NK-LGLL) respectively expressed surface KLRG1. The humanized afucosylated anti-KLRG1 monoclonal antibody (mAb208) optimized for mouse in vivo use depleted KLRG1+ TCL cells by mechanisms of ADCC, ADCP and CDC rather than apoptosis. mAb208 induced ADCC and ADCP of T-LGLL patient-derived CD8+/CD57+ cells ex vivo. mAb208 effected ADCC of subsets of healthy donor-derived KLRG1+ NK, CD4+, CD8+ Tem and TemRA cells while sparing KLRG1- naive and CD8+ Tcm cells. Treatment of cell line and TCL patient-derived xenografts with mAb208 or anti-CD47 mAb alone and in combination with the PI3K-δ/γ inhibitor, duvelisib extended survival. The depletion of macrophages in vivo antagonized mAb208 efficacy. CONCLUSIONS: Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms.

Coping and Perception of Prognosis in Patients With Indolent Non-Hodgkin's Lymphoma.

BACKGROUND: Indolent non-Hodgkin's lymphomas (iNHL) are a heterogenous group of mostly incurable diseases with prolonged illness courses and prognostic uncertainty. Yet, studies evaluating coping and perception of prognosis are limited. METHODS: We conducted a cross-sectional study of adults newly diagnosed with iNHL in the past 3 months at a single academic center. We assessed quality of life (QOL: Functional Assessment of Cancer Therapy-General), psychological symptoms (Hospital Anxiety and Depression Scale), coping (Brief-COPE), and perception of prognosis (Prognosis Awareness Impact Scale). RESULTS: We enrolled 70.6% (48/68) of eligible patients. Patients had older age (mean = 66.9,sd = 10.5), were female (60.4%), predominantly identified as White (85.4%), and had at least received a college degree (75%). Chronic lymphocytic leukemia (39.6%) and follicular lymphoma (33.3%) were the most common diagnoses. Overall, 27.1% and 14.6% of patients reported clinically significant anxiety and PTSD symptoms, respectively. Patients highly utilized acceptance (56.2%), seeking emotional support (47.9%), and denial (47.9%) as coping strategies at diagnosis. While 66.7% of patients recalled their oncologist assessment of illness as incurable, only 35.4% reported that the illness is unlikely to be cured. Overall, 45.8% indicated that they were worried about prognosis and 31.2% reported perseverating on their prognosis. Higher emotional coping with prognosis was associated with fewer anxiety (B = -0.6, SE = 0.2, P < .001), depression (B = -0.3, SE = .1, P = .005), and PTSD (B = -1.3, SE = 0.4, P < .001) symptoms and better QOL (B = 1.7, SE = 0.4, P < .001). DISCUSSION: Patients with iNHL report substantial psychological distress, a diversity of coping strategies, and complex cognitive understanding of their prognosis. Interventions, which address prognostic uncertainty and promote positive emotional coping with prognosis, may ameliorate psychological distress in this population.

Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited. METHODS: We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a 5-year period. RESULTS: Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ±â€…4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1-0.7; P = .010). CONCLUSIONS: CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted.

Clinical Outcomes and Health Care Utilization in Patients With Burkitt Lymphoma.

PURPOSE: Burkitt lymphoma is an aggressive B-cell lymphoma requiring intensive therapy, which places patients at risk for severe toxicity. However, few studies have described these patients' clinical outcomes and health care utilization, particularly among older adults. METHODS: We conducted a retrospective analysis of adults 40 years and older with Burkitt lymphoma at Massachusetts General Hospital and Dana-Farber Cancer Institute from February 1999 to December 2020 (N = 97). We abstracted patient characteristics, clinical outcomes, and health care utilization (unplanned hospitalizations, intensive care unit [ICU] admissions) during therapy from the electronic health record. Using univariate logistic regression, we examined factors associated with rates of unplanned hospitalization and ICU admission during therapy. RESULTS: Among evaluable patients (median age, 69 years; 23.7% female; 19.3% with bone marrow involvement), 45.8% (38 of 83) experienced unplanned hospitalization and 23.2% (19 of 82) experienced ICU admission during therapy. Among those 70 years and older, rates of unplanned hospitalization and ICU admission were 36.8% (14 of 38) and 29.0% (11 of 38), respectively. Bone marrow involvement (odds ratio [OR], 3.00; P = .069) was associated with a nonsignificantly greater likelihood of unplanned hospitalization. Older age (OR, 1.06; P = .039), Charlson comorbidity index >0 (OR, 3.14; P = .038), and hypoalbuminemia (OR, 3.22; P = .035) were associated with greater likelihood of ICU admission. Overall, 8.7% (8 of 92) of patients died during treatment, all of whom were 70 years and older. CONCLUSION: Adults with Burkitt lymphoma experience substantial rates of unplanned hospitalizations and ICU admissions, with older adults at especially high risk for ICU admission and death during treatment. Our findings underscore the need to develop supportive care interventions for patients with Burkitt lymphoma to help improve clinical outcomes and health care utilization.

Geriatric assessment measures are predictive of outcomes in chronic lymphocytic leukemia.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) commonly affects older adults. However, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in this population. Here, we aim to evaluate the use of a comprehensive geriatric assessment in older (>65 years) untreated patients with CLL to predict outcomes. MATERIALS AND METHODS: We conducted a planned analysis of 369 patients with CLL age 65 or older treated in a phase 3 randomized trial of bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone (A041202). Patients underwent evaluations of geriatric domains including functional status, psychological status, social activity, cognition, social support, and nutritional status. We examined associations among baseline geriatric domains with grade 3+ adverse events using multivariable logistic regression and overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models. RESULTS: In this study, the median age was 71 years (range: 65-87). In the combined multivariable model, the following geriatric domains were significantly associated with PFS: Medical Outcomes Study (MOS) - social activities survey score (hazard ratio [HR] [95% confidence interval (CI)] 0.974(0.961, 0.988), p = 0.0002) and nutritional status (≥5% weight loss in the preceding six months: (HR [95% CI] 2.717[1.696, 4.354], p < 0.001). MOS - social activities score [HR (95% CI) 0.978(0.958, 0.999), p = 0.038] was associated with OS. No geriatric domains were significantly associated with toxicity. There were no statistically significant interactions between geriatric domains and treatment. DISCUSSION: Geriatric domains of social activity and nutritional status were associated with OS and/or PFS in older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during treatment.

Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). To date, few studies have examined risk factors for AKI at engraftment, or the relationship between AKI and clinical outcomes. This study examined the incidence and risk factors for periengraftment AKI, as well as the association between AKI and overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of adult patients undergoing reduced-intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Periengraftment (day 0 to day 30) AKI incidence and severity were defined using modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Factors associated with periengraftment AKI risk were examined using Cox regression analysis. The impact of periengraftment AKI on OS and NRM (defined as death without recurrent disease after HCT), was evaluated using Cox regression and the Fine and Gray competing risks model, respectively. Kidney recovery, defined as a return of serum creatinine (SCr) to within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 post-HCT. Periengraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days (interquartile range, 4 to 30 days) post-transplantation. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.20 to 2.03; P < .001), fludarabine/melphalan conditioning (HR, 1.35, 95% CI, 1.01 to 1.81; P = .05, compared to fludarabine/busulfan and fludarabine, cyclophosphamide, and total body irradiation), HCT Comorbidity Index ≥4 (HR, 1.43; 95% CI, 1.14 to 1.79; P = .002), albumin <3.4 g/dL (HR, 2.04; 95% CI, 1.33 to 3.12; P = .001), hemoglobin ≤12 (HR, 1.96; 95% CI, 1.38 to 2.78; P < .001), supratherapeutic tacrolimus (HR, 1.45; 95% CI, 1.07 to 1.95; P = .02), and baseline SCr >1.1 mg/dL (HR, 1.87; 95% CI, 1.48 to 2.35; P < .001). Periengraftment AKI was associated with worse OS (HR, 1.40; 95% CI, 1.16 to 1.71; P < .001) and NRM (subdistribution HR, 2.10; 95% CI, 1.52 to 2.89; P < .001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, stage 2, and stage 3 AKI without KRT, respectively, and 4 of 16 patients (25%) were liberated from KRT. Periengraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for periengraftment AKI. Its association with worse OS and NRM underscores the importance of timely recognition and management.

Longitudinal patient-reported outcomes in patients receiving chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment for relapsed/refractory hematologic malignancies; however, data on patient-reported outcomes in CAR-T are limited. We conducted a longitudinal study of adults with hematologic malignancies receiving CAR-T. We assessed quality of life (QOL; functional assessment of cancer therapy-general), psychological distress (hospital anxiety and depression scale, patient health questionnaire-9, posttraumatic stress disorder [PTSD] checklist), and physical symptoms (Edmonton symptom assessment scale-revised) at baseline, 1 week, 1, 3, and 6 months after CAR-T. We used linear mixed models to identify factors associated with QOL trajectory. We enrolled 103 of 142 eligible patients (3 did not receive CAR-T). QOL (B = 1.96; P < .001) and depression (B = -0.32; P = .001) worsened by 1 week and improved by 6 months after CAR-T. At 6 months, 18%, 22%, and 22% reported clinically significant depression, anxiety, and PTSD symptoms, respectively. At 1 week, 52% reported severe physical symptoms, declining to 28% at 6 months after CAR-T. In unadjusted linear mixed models, worse Eastern Cooperative Oncology Group performance status (B = 1.24; P = .042), receipt of tocilizumab (B = 1.54; P = .042), and receipt of corticosteroids for cytokine release syndrome and/or neurotoxicity (B = 2.05; P = .006) were associated with higher QOL trajectory. After CAR-T, QOL declined, and depression increased early, followed by improvements in QOL, psychological distress, and physical symptoms by 6 months after infusion. A significant minority of patients reported substantial psychological distress and physical symptoms longitudinally.

Quality of Life, Physical Functioning, and Psychological Distress of Older Adults Undergoing Hematopoietic Stem Cell Transplantation.

With advances in therapies for hematologic cancers, older adults increasingly undergo hematopoietic stem cell transplantation (HSCT). Older adults may potentially experience an exaggerated burden of toxicity from HSCT. Studies examining the quality of life (QOL), physical functioning, and psychological symptom trajectory for older adults undergoing HSCT are limited. Our primary aim was to describe the trajectory of QOL, physical functioning, and psychological distress of older adults undergoing HSCT. Secondarily, we aimed to compare the trajectory of QOL, physical functioning, and psychological distress of older and younger adults undergoing HSCT and to evaluate factors associated with QOL trajectory in older adults undergoing HSCT. We conducted secondary analyses of two prospective studies conducted at Massachusetts General Hospital. From 2011 to 2016, we enrolled 250 adults undergoing allogeneic or autologous HSCT. Older age was defined as age ≥65 years. We collected patient-reported outcomes (PROs) within 72 hours of admission for HSCT, at hematologic nadir (2 weeks), and at 6 months after HSCT. To assess QOL, physical functioning, and psychological symptoms, we used the Functional Assessment of Cancer Therapy (FACT)-Bone Marrow Transplant, FACT-Trial Outcome Index, and Patient Health Questionnaire-9, respectively. We used the post-traumatic stress disorder (PTSD) Checklist-Civilian Version to assess PTSD symptoms. We fit linear mixed effects models to characterize trajectories of changes in PROs across timepoints and to evaluate baseline factors associated with QOL trajectories in older adults. Overall 30.4% (76/250) of our cohort was 65 years or older. All older adults undergoing allogeneic HSCT received a reduced intensity conditioning regimen. At 2 weeks after HSCT, older patients experienced a decline in QOL (Δ = -16.6, P < .001), physical functioning (Δ = -15.4, P < .001) and an increase in depression symptoms (Δ = 3.8, P < .001). At 6 months after HSCT, QOL (Δ = 1.4, P = .7), physical functioning (Δ = 1.7, P = .5), and depression symptoms (Δ = 0.4, P = .6) recovered to baseline values. At 6 months after HSCT, the proportion of older patients with PTSD symptoms increased from 5.3% (4/76) at baseline to 13.2% (10/76). There was no significant difference in slopes or trajectories of PROs between older and younger patients. In older adults, baseline psychological distress was associated with significantly worse QOL trajectory (Δ= -21.6, P ≤ .001). Older adults experienced a sharp decline in QOL and physical functioning and an increase in depression symptoms within 2 weeks of HSCT hospitalization. Baseline psychological distress was associated with a pronounced worsening in post-HSCT QOL trajectory. These findings underscore the need for supportive care interventions to improve the experience of older adults undergoing HSCT.

Delirium and Healthcare Utilization in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Delirium, a common neuropsychiatric syndrome among hospitalized patients, has been associated with significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Although delirium is often reversible with prompt diagnosis and appropriate management, timely screening of hospitalized patients, including HSCT recipients at risk for delirium, is lacking. The association between delirium symptoms and healthcare utilization among HSCT recipients is also limited. We conducted a retrospective analysis of 502 hospitalized patients admitted for allogeneic or autologous HSCT at 2 tertiary care hospitals between April 2016 and April 2021. We used Natural Language Processing (NLP) to identify patients with delirium symptoms, as defined by an NLP-assisted chart review of the electronic health record (EHR). We used multivariable regression models to examine the associations between delirium symptoms, clinical outcomes, and healthcare utilization, adjusting for patient-, disease-, and transplantation-related factors. Overall, 44.4% (124 of 279) of patients undergoing allogeneic HSCT and 39.0% (87 of 223) of those undergoing autologous HSCT were identified as having delirium symptoms during their index hospitalization. Two-thirds (139 of 211) of the patients with delirium symptoms were prescribed treatment with antipsychotic medications. Among allogeneic HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 7.960; P < .001), fewer days alive and out of the hospital (ß = -23.669; P < .001), and more intensive care unit admissions (odds ratio, 2.854; P = .002). In autologous HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 2.204; P < .001). NLP-assisted EHR review is a feasible approach to identifying hospitalized patients, including HSCT recipients at risk for delirium. Because delirium symptoms are negatively associated with health care utilization during and after HSCT, our findings underscore the need to efficiently identify patients hospitalized for HSCT who are at risk of delirium to improve their outcomes. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Sexual function remains persistently low in women after treatment for colorectal cancer and anal squamous cell carcinoma.

BACKGROUND: Women diagnosed with colorectal cancer (CRC) or anal squamous cell carcinoma (ASCC) are at high risk of sexual dysfunction after treatment, yet little is known about recovery and risk factors for chronic dysfunction. AIM: We aimed to describe sexual function and sexual activity among women who underwent definitive treatment for CRC or ASCC, examine relationships between time since treatment completion and sexual function, and explore factors associated with desire and changes in sexual desire over time. METHODS: As part of a prospective cohort study of patients with gastrointestinal cancer at the University of California San Francisco, female-identifying participants who finished definitive treatment for CRC or ASCC completed the Female Sexual Function Index (FSFI) at 6- to 12-month intervals. We used multivariable linear mixed models to explore factors associated with the FSFI desire subscale. OUTCOMES: Outcomes were rates of sexual activity, proportion at risk for sexual dysfunction (FSFI score <26.55), total FSFI score, and FSFI desire subscale. RESULTS: Among the 97 cancer survivors who completed at least 1 FSFI, the median age was 59 years, the median time since treatment end was 14 months, and 87% were menopausal. Fifty-five women (57%) had a history of colon cancer; 21 (22%), rectal cancer; and 21 (22%), ASCC. An additional 13 (13%) had a current ostomy. Approximately half the women were sexually active (n = 48, 49%). Among these 48 sexually active women, 34 (71%) had FSFI scores indicating risk for sexual dysfunction. Among the 10 sexually active women who completed a FSFI ≥2 years since end of treatment, the median total score was 22.6 (IQR, 15.6-27.3). None of the evaluated characteristics were associated with desire (age, tumor site, treatment, menopause status, or ostomy status). CLINICAL IMPLICATIONS: Consistent with prior studies, we found low desire scores after treatment for CRC or ASCC, with little recovery over time, suggesting that patients should not expect an eventual rebound of sexual function. STRENGTHS AND LIMITATIONS: Strengths of our study include longitudinal data and use of the validated FSFI. Women with ASCC composed 22% of our cohort, allowing for insight into this rare disease group. Limitations of this study include the small sample size, particularly for longitudinal analyses, and the enrollment of patients at variable times since treatment end. CONCLUSION: We observed a high prevalence of sexual health concerns, including low desire, after the treatment of CRC and ASCC that persisted for years after treatment was completed.

The Use of Natural Language Processing to Assess Social Support in Patients With Advanced Cancer.

BACKGROUND: Data examining associations among social support, survival, and healthcare utilization are lacking in patients with advanced cancer. METHODS: We conducted a cross-sectional secondary analysis using data from a prospective longitudinal cohort study of 966 hospitalized patients with advanced cancer at Massachusetts General Hospital from 2014 through 2017. We used NLP to identify extent of patients' social support (limited versus adequate as defined by NLP-aided review of the Electronic Health Record (EHR)). Two independent coders achieved a Kappa of 0.90 (95% CI: 0.84-1.00) using NLP. Using multivariable regression models, we examined associations of social support with: 1) OS; 2) death or readmission within 90 days of hospital discharge; 3) time to readmission within 90 days; and 4) hospital length of stay (LOS). RESULTS: Patients' median age was 65 (range: 21-92) years, and a plurality had gastrointestinal (GI) cancer (34.3%) followed by lung cancer (19.5%). 6.2% (60/966) of patients had limited social support. In multivariable analyses, limited social support was not significantly associated with OS (HR = 1.13, P = 0.390), death or readmission (OR = 1.18, P = 0.578), time to readmission (HR = 0.92, P = 0.698), or LOS (ß = -0.22, P = 0.726). We identified a potential interaction suggesting cancer type (GI cancer versus other) may be an effect modifier of the relationship between social support and OS (interaction term P = 0.053). In separate unadjusted analyses, limited social support was associated with lower OS (HR = 2.10, P = 0.008) in patients with GI cancer but not other cancer types (HR = 1.00, P = 0.991). CONCLUSION: We used NLP to assess the extent of social support in patients with advanced cancer. We did not identify significant associations of social support with OS or healthcare utilization but found cancer type may be an effect modifier of the relationship between social support and OS. These findings underscore the potential utility of NLP for evaluating social support in patients with advanced cancer.

Coping in caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

Caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) must cope with substantial caregiving burden, high rates of psychological distress, and diminished quality of life (QOL). However, data describing coping strategies before HSCT and the association between coping, QOL, and psychological outcomes in this population are lacking. We conducted a secondary analysis of data collected during a multisite randomized clinical trial of a supportive care intervention in HSCT recipients and their caregivers. Caregivers completed the Brief COPE, Hospital Anxiety and Depression Scale, and the Caregiver Oncology Quality of Life Questionnaire to measure coping strategies, psychological distress, and QOL, respectively. We grouped coping into 2 higher-order domains: approach-oriented (ie, emotional support and active coping) and avoidant (ie, self-blame and denial). We used the median split method to describe the distribution of coping and multivariate linear regression models to assess the relationship between coping and caregiver outcomes. We enrolled 170 caregivers, with a median (range) age of 53 (47-64) years. Most were White (87%), non-Hispanic (96%), and female (77%). Approach-oriented coping was associated with less anxiety (ß = -0.210, P = .003), depression symptoms (ß = -0.160, P = .009), and better QOL (ß = 0.526, P = .002). In contrast, avoidant coping was associated with more anxiety (ß = 0.687, P<.001), depression symptoms (ß = 0.579, P < .001), and worse QOL (ß = -1.631, P < .001). Our findings suggest that coping is related to distress and QOL among caregivers of HSCT recipients even before transplant. Hence, caregivers of patients with hematologic malignancies undergoing HSCT may benefit from resources that facilitate adaptive coping with the demands of caregiving.

Perception of prognosis, quality of life, and distress in patients receiving chimeric antigen receptor T-cell therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell is potentially curative therapy for patients with hematologic malignancies but can cause life-threatening toxicities. Data on perceptions of prognosis and psychological distress are lacking. METHODS: The authors conducted a cross-sectional study of patients receiving CAR-T. Before hospitalization for CAR-T, patients completed assessments of quality of life (QOL) (Functional Assessment of Cancer Therapy-General), anxiety and depression symptoms (Hospital Anxiety and Depression Scale) and post-traumatic stress disorder symptoms (Post-Traumatic Stress Checklist). Patients also completed the Prognostic Awareness Impact Scale (PAIS), which measures three domains: cognitive understanding of prognosis, emotional coping with prognosis, and adaptive response. RESULTS: A total of 71.8% (102 of 142) of eligible patients were enrolled. A total of 34% of patients reported that their oncologist said their cancer is curable and 64% reported there was >50% chance of cure. Overall, 26%, 30%, and 21% of patients reported clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, respectively. We found no association between patients' cognitive understanding of prognosis and QOL or mood. Higher emotional coping with prognosis was associated with better QOL (Β = 0.72; SE = 0.10; p = <.001) and lower depression (Β = -0.17; SE = 0.02; p = <.001), anxiety (Β = -0.21; SE = 0.02; p = <.001), and PTSD (Β = -0.43; SE = 0.06; p = <.001) symptoms. Higher adaptive response was associated with better QOL (Β = 0.19; SE = 0.09; p = .028) and lower depression (Β = -0.05; SE = 0.02; p = .023), anxiety (Β = -0.09; SE = 0.02; p = <.001), and PTSD (Β = -0.19; SE = 0.05; p = <.001) symptoms. CONCLUSIONS: Patients undergoing CAR-T report overly optimistic perception of their prognosis and have high rates of psychological distress. Higher emotional coping with prognosis and adaptive response were associated with better QOL and less psychological distress, underscoring the need to develop interventions to promote coping with this treatment. PLAIN LANGUAGE SUMMARY: Patients undergoing chimeric antigen receptor T-cell therapy experience report overly optimistic perceptions of their prognosis and have high rates of psychological distress. Notably, higher emotional coping with prognosis and adaptive response were associated with better quality of life and less psychological distress.