Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

We report on the first-in-human clinical trial using chimeric antigen receptor (CAR) T-cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies (clinicaltrials.gov NCT04136275). Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T-cells. CAR-37 T-cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4/5 patients. Tumor responses were observed in 4/5 patients, with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in two of these patients, efforts to ablate CAR-37 T-cells (which were engineered to co-express truncated EGFR) with cetuximab, were unsuccessful. Hematopoiesis was restored in these two patients following allogeneic hematopoietic stem cell transplantation. No other severe, non-hematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T-cells in response to hematopoietic stem cells in vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of IL-18, with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37-treated patients relative to both cytopenic and non-cytopenic cohorts of CAR-19-treated cohorts of patients. In conclusion, CAR-37 T-cells exhibited anti-tumor activity, with significant CAR expansion and cytokine production. CAR-37 T-cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant.

Integrating Palliative Care and Hematologic Malignancies: Bridging the Gaps for Our Patients and Their Caregivers.

Patients with hematologic malignancies (HMs) struggle with immense physical and psychological symptom burden, which negatively affect their quality of life (QOL) throughout the continuum of illness. These patients are often faced with substantial prognostic uncertainty as they navigate their illness course, which further complicates their medical decision making, especially at the end of life (EOL). Consequently, patients with HM often endure intensive medical care at the EOL, including frequent hospitalization and intensive care unit admissions, and they often die in the hospital. Our EOL health care delivery models are not well suited to meet the unique needs of patients with HMs. Although studies have established the role of specialty palliative care for improving QOL and EOL outcomes in patients with solid tumors, numerous disease-, clinician-, and system-based barriers prevail, limiting the integration of palliative care for patients with HMs. Nonetheless, multiple studies have emerged over the past decade identifying the role of palliative care integration in patients with various HMs, resulting in improvements in patient-reported QOL, symptom burden, and psychological distress, as well as EOL care. Importantly, these studies have also identified active components of specialty palliative care interventions, including strategies to promote adaptive coping especially in the face of prognostic uncertainty. Future work can leverage the knowledge gained from specialty palliative care integration to develop and test primary palliative care interventions by training clinicians caring for patients with HMs to incorporate these strategies into their clinical practice.

Outcomes of a Formal Hematopoietic Cell Transplantation Survivorship Program on Screening for Late Effects.

Allogeneic hematopoietic cell transplantation (HCT) survivors may benefit from routine screening for post-transplant complications. However, the impact of formal survivorship efforts to promote screening adherence is uncertain. The effect of a formal HCT survivorship program to promote screening adherence was evaluated. We conducted a retrospective analysis of an academic formal HCT survivorship program with primary and specialty consult components. We included patients who underwent allogeneic HCT and were alive and relapse-free 1-year post-HCT. We excluded patients who died <2-year post-HCT or transferred care. We measured screening adherence to cardiovascular, pulmonary, ocular, secondary cancer, and endocrine evaluations. The primary outcome was proportion of patients completing ≥1 evaluation per screening domain prior to 2-year post-HCT. We examined screening adherence during 3 time periods: presurvivorship (2012 to 2014) and 2 postsurvivorship (2016 to 2018 and 2019 to 2021) using multivariate logistic and Cox proportional hazards regression. Four hundred ten patients (2012 to 2014: n = 136, 2016 to 2018: n = 153, 2019 to 2021: n = 121) were included. Compared to the presurvivorship period (16.9%), patients in 2016 to 2018 (47.7%, odds ratio [OR] = 4.9, P < .0001) and 2019 to 2021 (34.7%, OR = 2.7, P = .001) were more likely to complete ≥1 evaluation per screening domain. Except for pulmonary function tests in 2019 to 2021, median time to completion of survivorship evaluations was shorter in the survivorship periods compared to presurvivorship. Patients who completed a formal HCT survivorship consult in 2016 to 2018 and 2019 to 2021 were more likely to complete ≥1 evaluation per screening domain (OR = 5.1, P = .0004). Survivorship consult had similar effect on the primary screening outcome in 2016 to 2018 and 2019 to 2021 (consult × time interaction OR: 2.5, P = .2). However, patients who received a consult in 2019 to 2021 were more likely to complete all screenings (consult × time interaction: OR = 5.7, P = .03). Our HCT survivorship program with primary and specialty components improved screening adherence. Additional studies are needed to evaluate efficacy, dissemination, and implementation of formal HCT survivorship programs.

A novel psychosocial virtual reality intervention (BMT-VR) for patients undergoing hematopoietic stem cell transplantation: Pilot randomized clinical trial design and methods.

BACKGROUND: Although patients undergoing hematopoietic stem cell transplantation (HSCT) must cope with psychological distress and isolation during an extended transplant hospitalization, psychosocial interventions to address these unmet needs are lacking. Virtual reality offers an innovative modality to deliver a patient-centered psychosocial intervention to address psychosocial needs of patients undergoing HSCT. However, there are currently no supportive care interventions leveraging virtual reality in patients undergoing HSCT. OBJECTIVE: To describe the methods of a randomized clinical trial (RCT) to assess the feasibility and preliminary efficacy of a self-administered, virtual reality-delivered psychosocial intervention (BMT-VR) to improve psychological distress and quality of life (QOL) for patients hospitalized for HSCT. METHODS: This study entails a single-center RCT of BMT-VR compared to usual transplant care in 80 patients hospitalized for HSCT. Adult patients with hematologic malignancies hospitalized for autologous or allogeneic HSCT are eligible. BMT-VR includes psychoeducation about the HSCT process, psychosocial skill building to promote effective coping and acceptance, and self-care and positive psychology skills to promote post-HSCT recovery. The primary aim is to assess the feasibility defined a priori as ≥60% of eligible patients enrolling in the study, and of those enrolled and randomized to the BMT-VR, ≥ 60% completing 4/6 BMT-VR modules. Secondary objectives include assessing the preliminary effects on psychological distress and QOL. DISCUSSION: This is the first RCT of a virtual reality-delivered psychosocial intervention for the HSCT population. If deemed feasible, a future larger multi-site clinical trial can evaluate the efficacy of BMT-VR on outcomes for patients hospitalized for HSCT.

The Edmonton Symptom Assessment System is a valid, reliable, and responsive tool to assess symptom burden in decompensated cirrhosis.

BACKGROUND: While there is a growing need for interventions addressing symptom burden in patients with decompensated cirrhosis (DC), the lack of validated symptom assessment tools is a critical barrier. We investigated the psychometric properties of the revised Edmonton Symptom Assessment System (ESAS-r) in a longitudinal cohort of patients with DC. METHODS: Adult outpatients with DC were prospectively recruited from a liver transplant center and completed ESAS-r at baseline and week 12. We examined reliability, floor/ceiling effects, structural validity, and known-groups validity. We examined the convergent and predictive validity of ESAS-r with health-related quality of life using the Short Form Liver Disease Quality of Life (SF-LDQOL) and responsiveness to changes in anxiety and depression using the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 from baseline to week 12. RESULTS: From August 2018 to September 2022, 218 patients (9% Child-Pugh A, 59% Child-Pugh B, and 32% Child-Pugh C) were prospectively recruited and completed the ESAS-r, SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale at baseline and week 12 (n = 135). ESAS-r had strong reliability (Cronbach's alpha 0.86), structural validity (comparative fit index 0.95), known-groups validity (Child-Pugh A: 25.1 vs. B: 37.5 vs. C: 41.4, p = 0.006), and convergent validity (r = -0.67 with SF-LDQOL). Floor effects were 9% and ceiling effects were 0.5%. Changes in ESAS-r scores from baseline to week 12 significantly predicted changes in SF-LDQOL (ß = -0.36, p < 0.001), accounting for 30% of the variation. ESAS-r was strongly responsive to clinically meaningful changes in SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale. CONCLUSIONS: ESAS-r is a reliable, valid, and responsive tool for assessing symptom burden in patients with DC and can predict changes in health-related quality of life. Future directions include its implementation as a key outcome measure in cirrhosis care and clinical trials.

Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract.

ABSTRACT: Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577.

Hospital-Level Care at Home for Patients with Cirrhosis.

BACKGROUND: Patients with cirrhosis have a 30-day readmission rate of over 30%. Novel care delivery models are needed to reduce healthcare costs and utilization associated with cirrhosis care. One such model is Home Hospital (HH), which provides inpatient-level care at home. Limited evidence currently exists supporting HH for cirrhosis patients. AIMS: The aims of this study were to characterize patients with cirrhosis who received hospital-level care at home in a two-site clinical trial and to describe the care they received. Secondary aims included describing their outcomes, including adverse events, readmissions and mortality. METHODS: We identified all patients with cirrhosis who enrolled in HH as part of a two-site clinical trial between 2017 and 2022. HH services include daily clinician visits, intravenous and oral medications, continuous vital sign monitoring, and telehealth specialist consultation. We collected sociodemographic data and analyzed HH stays, including interventions, outcomes, adverse events, and follow-up. RESULTS: 22 patients with cirrhosis (45% Hispanic; 50% limited English proficiency, median MELD-Na 12) enrolled in HH during the study period. Interventions included lab chemistries (82%), intravenous medications (77%), specialist consultation (23%), and advanced diagnostics/procedures (23%). The median length of stay was 7 days (IQR 4-12); 186 bed-days were saved. Two patients (9%) experienced adverse events (AKI). No patients required escalation of care; 9% were readmitted within 30 days. CONCLUSIONS: In this two-site study, HH was feasible for patients with cirrhosis, holding promise as a hepatology delivery model. Future randomized trials are needed to further evaluate the efficacy of HH for patients with cirrhosis.

Trajectories of physical well-being among adults with acute myeloid leukemia.

ABSTRACT: Patients with acute myeloid leukemia (AML) often undergo physical decline leading to negative outcomes. Identification of distinct trajectories may help guide clinical decision-making and supportive care interventions. We built group-based trajectory models (GBTM) to find trajectories of change in the Functional Assessment of Cancer Therapy Physical Well-Being (FACT-PWB) subscale (up to 5 time points over 0 to 200 days of follow-up) using data from adults with newly diagnosed AML in 4 supportive care studies. We also estimated the association of baseline characteristics (age, marital status, education, AML risk, baseline FACT-PWB, depression, and anxiety) with group membership. Among 343 patients with ≥2 FACT-PWB scores, mean age was 69.6 years (standard deviation, 12.1); most had intermediate-risk AML (n = 178 [51.8%]), received intensive treatment (n = 244 [71.1%]), and died during follow-up (n = 199 [58.0%]). The GBTM with 4 distinct trajectories showed the best fit. The largest group (n = 153 [45.0%]) showed slight improvement, whereas the smallest (n = 8 [2.4%]) experienced early decline with later improvement. Baseline FACT-PWB was the only characteristic statistically significantly associated with group membership. Adults with AML show distinct trajectories of physical well-being, and many experience some decline. Exploring trajectories of self-reported and objective physical function may inform decision-making and interventions. These trials were registered at www.ClinicalTrials.gov as #NCT02975869, #NCT03310918, and #NCT03372291.

A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

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.

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.

Gratitude, optimism, and satisfaction with life and patient-reported outcomes in patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: Associations between positive psychological well-being (PPWB) and patient-reported outcomes (PROs, e.g., quality of life [QOL]) have yet to be studied extensively in patients with hematologic malignancies who are allogeneic hematopoietic stem cell transplant (HSCT) survivors, despite substantial evidence that PPWB impacts PROs of other medical populations. METHODS: We conducted a secondary analysis of cross-sectional data examining the association of PPWB and PROs at day 100 post-transplant among 158 allogeneic HSCT recipients. Optimism, gratitude, life satisfaction, and PROs (i.e., QOL, anxiety, depression, and PTSD symptoms) were assessed using the Life Orientation Test-Revised, Gratitude Questionnaire, Satisfaction with Life Scale, Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Hospital Anxiety and Depression Scale, and Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, respectively. We used linear and multivariate regressions for all analyses and controlled for patient factors. RESULTS: Optimism was associated with better QOL (ß = 1.46; p < 0.001) and lower levels of anxiety (ß = -0.28; p < 0.001), depression (ß = -0.31; p < 0.001), and PTSD (ß = -0.58; p < 0.001). Gratitude was associated with better QOL (ß = 1.11; p < 0.001) and lower levels of anxiety (ß = -0.21; p = 0.001), depression (ß = -0.14; p = 0.021), and PTSD (ß = -0.32; p = 0.032). Finally, satisfaction with life was associated with better QOL (ß = 1.26; p < 0.001) and lower levels of anxiety (ß = -0.18; p < 0.001), depression (ß = -0.21; p < 0.001), and PTSD (ß = -0.49; p < 0.001). CONCLUSION: Optimism, gratitude, and satisfaction with life were all associated with better QOL and lower levels of psychological distress in allogeneic HSCT survivors. These data support studies to harness PPWB as a therapeutic intervention for this population throughout HSCT recovery.

Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease.

BACKGROUND: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.

Coping in patients with hematologic malignancies undergoing hematopoietic cell transplantation.

ABSTRACT: Patients undergoing hematopoietic cell transplantation (HCT) must cope with physical and psychological symptoms. Yet, studies examining pre-HCT coping are limited. We aimed to characterize pre-HCT coping, evaluate the association of coping with baseline quality of life (QOL) and psychological distress, and identify sociodemographic factors associated with pre-HCT coping. We conducted a cross-sectional analysis of baseline data from a multisite randomized supportive care intervention trial among patients with hematologic malignancies undergoing allogeneic or autologous HCT. We assessed patient-reported QOL, psychological distress, and coping within 72 hours of admission for HCT. We used the median split method to dichotomize coping and multivariate regression analyses to characterize the association of coping with psychological distress and QOL. Of patients awaiting HCT (n = 360; mean age, 55.4 years; 49.7% autologous), 43.5% were high users of approach-oriented coping, whereas 31.3% were high users of avoidant coping. Patients reported high use of emotional support (60.9%), acceptance (51.2%), self-blame (33%), and denial (31.3%). Older age (≥65 years) was associated with less frequent use of avoidant coping (odds ratio, 0.5; P = .01). Approach-oriented coping was associated with better pre-HCT QOL (Beta(B) = 6.7; P = .001), and lower depression (B = -1.1; P = .001) and anxiety (B = -0.9; P = .02) symptoms. Avoidant coping was associated with worse pre-HCT QOL (B = -13.3; P < .001) and symptoms of depression (B = 1.9; P < .001), anxiety (B = 3.1; P < .001), and posttraumatic stress disorder (B = 8.1; P < .001). Pre-HCT coping is strongly associated with psychological distress and QOL. These data support the need for interventions to address coping during HCT hospitalization. This clinical trial was registered at www.clinicaltrials.gov as #NCT03641378.

Protocol for multi-site randomized trial of inpatient palliative care for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

BACKGROUND: Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) commonly experience debilitating physical and psychological symptoms during a 3-4-week-hospitalization. During hospitalization, caregivers (i.e., family and friends) also endure immense emotional stress as they witness their loved one struggle with HSCT toxicities. Yet interventions to improve quality of life (QOL) and reduce psychological distress during HSCT are limited. METHODS: We are conducting a multi-site randomized controlled trial of inpatient integrated palliative and transplant care versus usual care in 360 patients hospitalized for HSCT and their caregivers at three academic centers. Intervention participants meet with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care receive all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assess patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD checklist), symptom burden (Edmonton Symptom Assessment Scale), and fatigue (FACT-Fatigue) as well as caregiver-reported outcomes at baseline, 2 weeks, 3-months, 6-months, and 12-months post-HSCT. The primary endpoint is to compare QOL at week-2 during HSCT hospitalization between the two groups when patients typically experience their QOL nadir during HSCT. CONCLUSIONS: This multi-site trial will define the role of palliative care for improving QOL and care for patients with hematologic malignancies undergoing HSCT and their caregivers.

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.