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.

Ameliorating Racial Disparities in Vascular Risk Factor Management With Aggressive Medical Management in the SAMMPRIS Trial.

BACKGROUND: The WASID trial (Warfarin-Aspirin Symptomatic Intracranial Disease) and the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) evaluated optimal management of symptomatic intracranial atherosclerotic stenosis. The aim of this retrospective, observational study was to determine whether aggressive medical management used in the SAMMPRIS trial ameliorated disparities in risk factor control between Black and non-Black patients. METHODS: The SAMMPRIS trial was a randomized controlled trial that enrolled patients with symptomatic intracranial atherosclerotic stenosis between November 2008 and April 2011. The frequency of risk factors at study entry (baseline) and mean levels of systolic blood pressure, diastolic blood pressure, LDL (low-density lipoprotein), hemoglobin A1c, and exercise level (quantified by physician-based assessment and counseling for exercise score) at baseline and at 1 year of follow-up were compared between Black (n=104) versus non-Black patients (n=347). RESULTS: Significant differences at baseline in Black patients (listed first) versus non-Black patients were age (57.5 versus 61.0 years; P=0.004), hypertension (95.2% versus 87.5%; P=0.027), diabetes (52.9% versus 39.7%; P=0.017), mean diastolic blood pressure (82.4 versus 79.5 mm Hg; P=0.035), and mean physician-based assessment and counseling for exercise score (2.7 versus 3.3; P=0.002). The mean diastolic blood pressure and mean physician-based assessment and counseling for exercise scores at 1 year in Black versus non-Black patients were 74.7 versus 75.5 mm Hg (P=0.575) and 4.2 versus 4.1 (P=0.593), respectively. No disparities in other modifiable risk factors emerged at 1 year. CONCLUSIONS: Significant differences in important risk factors (physical activity and diastolic blood pressure) at baseline between Black and non-Black patients resolved at 1 year, suggesting that aggressive medical management may have an important role in ameliorating disparities in risk factor control between Black and non-Black patients.

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.

Inflammatory cytokines and depression symptoms following hematopoietic cell transplantation.

Increased synthesis and release of inflammatory signalling proteins is common among individuals with hematologic malignancies undergoing hematopoietic cell transplantation (HCT) due to intensive conditioning regimens and complications such as graft-versus-host-disease and infections. Prior research indicates that inflammatory responses can activate central nervous system pathways that evoke changes in mood. This study examined relationships between markers of inflammatory activity and depression symptoms following HCT. Individuals undergoing allogeneic (n = 84) and autologous (n = 155) HCT completed measures of depression symptoms pre-HCT and 1, 3, and 6 months post-HCT. Proinflammatory (IL-6, TNF-α) and regulatory (IL-10) cytokines were assessed by ELISA in peripheral blood plasma. Mixed-effects linear regression models indicated that patients with elevated IL-6 and IL-10 reported more severe depression symptoms at the post-HCT assessments. These findings were replicated when examining both allogeneic and autologous samples. Follow-up analyses clarified that relationships were strongest for neurovegetative, rather than cognitive or affective, symptoms of depression. These findings suggest that anti-inflammatory therapeutics targeting an inflammatory mediator of depression could improve quality of life of HCT recipients.

Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance.

Macrophage antibody (Ab)-dependent cellular phagocytosis (ADCP) is a major cytotoxic mechanism for both therapeutic unconjugated monoclonal Abs (mAbs) such as rituximab and Ab-induced hemolytic anemia and immune thrombocytopenia. Here, we studied the mechanisms controlling the rate and capacity of macrophages to carry out ADCP in settings of high target/effector cell ratios, such as those seen in patients with circulating tumor burden in leukemic phase disease. Using quantitative live-cell imaging of primary human and mouse macrophages, we found that, upon initial challenge with mAb-opsonized lymphocytes, macrophages underwent a brief burst (<1 hour) of rapid phagocytosis, which was then invariably followed by a sharp reduction in phagocytic activity that could persist for days. This previously unknown refractory period of ADCP, or hypophagia, was observed in all macrophage, mAb, and target cell conditions tested in vitro and was also seen in vivo in Kupffer cells from mice induced to undergo successive rounds of αCD20 mAb-dependent clearance of circulating B cells. Importantly, hypophagia had no effect on Ab-independent phagocytosis and did not alter macrophage viability. In mechanistic studies, we found that the rapid loss of activating Fc receptors from the surface and their subsequent proteolytic degradation were the primary mechanisms responsible for the loss of ADCP activity in hypophagia. These data suggest hypophagia is a critical limiting step in macrophage-mediated clearance of cells via ADCP, and understanding such limitations to innate immune system cytotoxic capacity will aid in the development of mAb regimens that could optimize ADCP and improve patient outcome.

Relationship Between Longitudinal Coping Strategies and Outcomes in Patients With Acute Myeloid Leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) face an abrupt life-threatening illness and experience immense physical and psychological symptoms. However, no data describe how patients with AML cope longitudinally with their illness or the relationship between longitudinal coping and outcomes. METHODS: We conducted a secondary analysis of longitudinal data from 160 patients with high-risk AML enrolled in a supportive care intervention trial to describe coping strategies longitudinally across the illness course. We used the Brief COPE questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, and the Functional Assessment of Cancer Therapy-Leukemia to measure coping strategies, psychological distress, and quality of life (QoL) at baseline and at weeks 2, 4, 12, and 24 after diagnosis. Electronic health records were used to assess healthcare utilization and end-of-life (EoL) outcomes, and multivariate analyses were used to assess the relationship between coping and outcomes. RESULTS: Longitudinal utilization of approach-oriented coping strategies was significantly associated with less distress (anxiety: ß, -0.18; P<.001; depression symptoms: ß, -0.42; P<.001; PTSD symptoms: ß, -0.60; P<.001) and better QoL (ß, 2.00; P<.001). Longitudinal utilization of avoidant coping strategies was significantly associated with greater distress (anxiety: ß, 0.64; depression symptoms: ß, 0.54; PTSD symptoms: ß, 2.13; P<.001 for all) and worse QoL (ß, -4.27; P<.001). Although the use of approach-oriented and avoidant coping strategies was not significantly associated with hospitalization, chemotherapy administration, or hospice use in the last 30 days of life, approach-oriented coping was associated with lower odds of ICU admissions (odds ratio, 0.92; P=.049). CONCLUSIONS: Longitudinal use of approach-oriented coping strategies was associated with less psychological distress, better QoL, and a lower likelihood of ICU admission, suggesting a possible target for supportive oncology interventions. Coping strategies did not impact EoL outcomes, and further research is needed to elucidate which patient factors impact EoL decision-making.

Fatigue Perpetuating Factors as Mediators of Change in a Cognitive Behavioral Intervention for Targeted Therapy-Related Fatigue in Chronic Myeloid Leukemia: A Pilot Study.

BACKGROUND: Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). PURPOSE: The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. METHODS: Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. RESULTS: A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p's ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p's ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. CONCLUSIONS: CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings.

Correlates of fatigue severity in patients with chronic myeloid leukemia treated with targeted therapy.

PURPOSE: Tyrosine kinase inhibitors (TKIs) substantially improve survival for patients with chronic myeloid leukemia (CML), but fatigue associated with TKIs can negatively impact patients' quality of life and adherence. This study sought to identify correlates of fatigue (e.g., sociodemographic characteristics, clinical characteristics, health behaviors) among patients with CML taking TKIs who reported moderate to severe fatigue. METHODS: Adults with CML experiencing at least moderate fatigue were recruited for a pilot trial of a cognitive behavioral intervention to improve fatigue. Data collected pre-intervention were used to explore concurrent correlates of fatigue in univariate and multivariable models. RESULTS: Participants (N = 44, 48% female) were M = 55.6 years old (SD = 12.6) and had been diagnosed with CML M = 5.2 years prior (SD = 5.3). Participants had been taking their current TKI for M = 2.5 years (SD = 2.7). Most participants (64%) had previously been treated with ≥ 1 other TKI. More than three-quarters of participants (77%) reported severe fatigue. In univariate models, worse fatigue was associated with higher BMI (r = -0.36, p = 0.018), prior treatment with other TKI(s) (r = - 0.34, p = 0.024), worse sleep disturbance (r = - 0.51, p < 0.001), and less physical activity (r = 0.31, p = 0.043). In a multivariable model, significant univariate correlates accounted for 39% of the variance in fatigue. Worse fatigue remained significantly correlated with higher BMI (ß = - 0.33, p = 0.009) and more disturbed sleep (ß = - 0.45, p < 0.001). CONCLUSION: Results may inform future research aiming to identify fatigued patients with CML at risk for experiencing more severe fatigue during TKI therapy. Identifying predictors of fatigue severity could aid clinicians in identifying which patients will benefit from referrals to supportive therapy. TRIAL REGISTRATION: NCT02592447, October 30, 2015.

Palliative care and coping in patients with acute myeloid leukemia: Mediation analysis of data from a randomized clinical trial.

BACKGROUND: It has been shown previously that integrated palliative care for patients with acute myeloid leukemia (AML) during intensive chemotherapy leads to improvements in quality of life (QOL) and mood. Coping has been shown to mediate palliative care interventions in advanced cancer; the mechanisms by which improvements occur among patients with AML remain unexplained. METHODS: The authors conducted a secondary analysis of data from a multisite randomized trial of integrated palliative and oncology care (IPC; n = 86) versus usual care (n = 74) for hospitalized patients with AML undergoing intensive chemotherapy. IPC patients met with palliative care at least twice weekly during their initial and subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the Brief Coping Orientation to Problems Experienced Inventory to assess QOL, mood, and coping at the baseline and at weeks 2, 4, 12, and 24. Linear regression models were used to assess the effect of IPC on coping. Causal mediation regression models were used to examine whether changes in coping mediated intervention effects on patient-reported outcomes at week 2. RESULTS: One hundred sixty eligible patients (68.1%) were enrolled. Those randomized to IPC reported improvements in approach-oriented coping (P < .01) and reductions in avoidant coping (P < .05). These changes in coping mediated the intervention effects on QOL (95% CI, 2.14-13.63), depression (95% CI, -2.05 to -0.27), and anxiety symptoms (95% CI, -1.25 to -0.04). Changes in approach-oriented and avoidant coping accounted for 78% of the total palliative care intervention effect on QOL, for 66% of the effect on depression, and for 35% of the effect on anxiety symptoms. CONCLUSIONS: Palliative care integrated during intensive chemotherapy for patients with AML facilitates coping strategy use. Improvement in coping skills accounts for a substantial proportion of the effect from a palliative care intervention on patient-reported outcomes.

Contribution of Sleep Disruption and Sedentary Behavior to Fatigue in Survivors of Allogeneic Hematopoietic Cell Transplant.

BACKGROUND: Fatigue is a prominent quality of life concern among recipients of hematopoietic cell transplantation (HCT). PURPOSE: The present study investigated whether objectively measured sleep efficiency and sedentary behavior are related to greater reports of fatigue. METHODS: Eighty-two allogeneic HCT recipients who were 1-5 years post-transplant and returning for a follow-up visit participated (age M = 56, 52% female, 56% leukemia). They wore an actigraph assessing sleep efficiency and sedentary behavior for one week and completed an electronic log assessing fatigue each evening during the same period. RESULTS: Twenty-six percent of patients reported clinically meaningful fatigue. On average, fatigue was mild (M = 2.5 on 0-10 scale, SD = 2.0), sleep was disturbed (sleep efficiency M = 78.9%, SD = 8.9), and patients spent the majority of time in sedentary (M = 55.4%, SD = 10.2) or light (M = 35.9%, SD = 8.6) activity. Multilevel model analysis of between-person differences indicated that patients who experienced less efficient sleep the previous evening provided greater evening reports of average fatigue, b = -0.06, 95% CI (-0.11, -0.01). Similarly, within-person analyses indicated that when patients experienced less efficient sleep the previous evening or were more sedentary as compared to their average, they provided greater evening reports of average fatigue, b = -0.02, 95% CI (-0.05, -0.004); b = 4.46, 95% CI (1.95, 6.97), respectively. CONCLUSIONS: Findings demonstrate that poor sleep and daily sedentary behavior are related to evening reports of fatigue and should be considered modifiable targets for intervention.

An examination of the relationship of patient modifiable and non-modifiable characteristics with fear of cancer recurrence among colorectal cancer survivors.

PURPOSE: Fear of cancer recurrence (FCR) is one of the most common and distressing issues affecting cancer survivors. This study examined (1) the association between modifiable cognitive, behavioral, and social characteristics and FCR, (2) the association between non-modifiable characteristics and FCR, and (3) the relative contributions of modifiable and non-modifiable characteristics to FCR. METHODS: Participants (n = 120) had been diagnosed with colorectal cancer and completed cancer treatment in the past 6 to 36 months. Participants completed self-report measures of modifiable cognitive (e.g., beliefs about worry), behavioral (e.g., health-related reassurance seeking), and social (e.g., social constraints) characteristics. Non-modifiable characteristics (e.g., age, disease severity) were assessed via self-report and medical record review. FINDINGS: Modifiable (i.e., perceived risk, self-efficacy, positive beliefs about worry, negative beliefs about worry, intolerance of uncertainty, rumination, reassurance seeking, health-related reassurance seeking, social constraints) and non-modifiable (i.e., age, gender, disease severity, neuroticism, conscientiousness) characteristics were associated with FCR (p's < .05). Hierarchical linear regression analyses demonstrated that modifiable characteristics accounted for an additional 15% of the variance (p < .001) beyond that accounted for by non-modifiable characteristics (R2 = .45, p < .001), with perceived risk (B = .35) and health-related reassurance seeking (B = .22) emerging as significant predictors of FCR (p's < .05). IMPLICATIONS: Results identify non-modifiable characteristics that may serve as risk factors for greater FCR and identify specific modifiable characteristics (i.e., perceived risk, health-related reassurance seeking) to be targeted by interventions to reduce FCR among cancer survivors.

Enhanced coping and self-efficacy in caregivers of stem cell transplant recipients: Identifying mechanisms of a multimodal psychosocial intervention.

BACKGROUND: In a recent trial, a 6-session intervention (BMT-CARE) integrating medical information with cognitive-behavioral strategies improved quality of life (QOL), mood, coping skills, and self-efficacy for family/friend caregivers of hematopoietic stem cell transplantation (HCT) recipients. This study examined whether improvements in coping and self-efficacy mediated the intervention effects on QOL and mood. METHODS: From December 2017 to April 2019, 100 caregivers of HCT recipients were enrolled into a randomized clinical trial of BMT-CARE versus usual care. Caregivers completed self-report measures of QOL (CareGiver Oncology Quality of Life questionnaire), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), coping skills (Measure of Current Status), and self-efficacy (Cancer Self-Efficacy Scale-Transplant) at enrollment (before HCT) and 60 days after HCT. Causal mediation regression models were used to examine whether changes in coping and self-efficacy mediated intervention effects on QOL as well as depression and anxiety symptoms. RESULTS: Improvements in 60-day QOL in patients assigned to BMT-CARE were partially mediated by improved coping and self-efficacy (indirect effect, 6.93; SE, 1.85; 95% CI, 3.71-11.05). Similarly, reductions in 60-day depression and anxiety symptoms were partially mediated by improved coping and self-efficacy (indirect effect for depression, -1.19; SE, 0.42; 95% CI, -2.23 to -0.53; indirect effect for anxiety, -1.46; SE, 0.55; 95% CI, -2.52 to -0.43). Combined improvements in coping and self-efficacy accounted for 67%, 80%, and 39% of the total intervention effects on QOL and depression and anxiety symptoms, respectively. CONCLUSIONS: Coping and self-efficacy are essential components of a brief psychosocial intervention that improves QOL and mood for caregivers of HCT recipients during the acute recovery period. LAY SUMMARY: A 6-session program (BMT-CARE) focused on providing medical information, caregiving skills, and self-care and coping strategies has been previously reported to improve the quality of life and mood of caregivers of hematopoietic stem cell transplantation recipients in comparison with caregivers who receive care as usual. Using statistical models, this study suggests that learning coping skills and improving self-efficacy are the most essential components of this program that likely lead to better quality of life and mood for caregivers.

Internet-assisted cognitive behavioral intervention for targeted therapy-related fatigue in chronic myeloid leukemia: Results from a pilot randomized trial.

BACKGROUND: Fatigue is a common and disabling side effect of targeted therapies such as tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). The goal of the current study was to conduct a pilot randomized trial of the first cognitive behavioral intervention developed for fatigue due to targeted therapy. METHODS: Patients with CML treated with a TKI who were reporting moderate to severe fatigue were recruited and randomized 2:1 to cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) delivered via FaceTime for the iPad or to a waitlist control (WLC) group. The outcomes were acceptability, feasibility, and preliminary efficacy for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue; primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General; secondary outcome). Participants were assessed before randomization and after treatment (ie, approximately 18 weeks later). RESULTS: A total of 44 patients (mean age, 55 years; 48% female) were assigned to CBT-TTF (n = 29) or WLC (n = 15). The study participation rate was 59%. Among the patients assigned to CBT-TTF, 79% completed the intervention. Intent-to-treat analyses indicated that patients assigned to CBT-TTF demonstrated greater improvements in fatigue (d = 1.06; P < .001) and overall quality of life (d = 1.15; P = .005) than those assigned to WLC. More patients randomized to CBT-TTF than WLC demonstrated clinically significant improvements in fatigue (85% vs 29%) and quality of life (88% vs 54%; P values ≤ .016). CONCLUSIONS: CBT-TTF displays preliminary efficacy in improving fatigue and quality of life among fatigued patients with CML treated with TKIs. The findings suggest that a larger randomized study is warranted.

Multimodal psychosocial intervention for family caregivers of patients undergoing hematopoietic stem cell transplantation: A randomized clinical trial.

BACKGROUND: Caregivers of patients undergoing hematopoietic stem cell transplantation (HCT) experience an immense caregiving burden before, during, and after HCT. METHODS: We conducted an unblinded, randomized trial of a psychosocial intervention (BMT-CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT-CARE or usual care. BMT-CARE was tailored to the HCT trajectory and integrated treatment-related education and self-care with cognitive-behavioral skills to promote coping. Caregivers assigned to BMT-CARE met with a trained interventionist (a psychologist or a social worker) in person, via telephone, or via videoconferencing for 6 sessions starting before HCT and continuing up to day +60 after HCT. The primary endpoint was feasibility, which was defined as at least 60% of eligible caregivers enrolling and completing 50% or more of the intervention sessions. We assesed caregiver quality of life (QOL; Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), psychological distress (Hospital Anxiety and Depression Scale), self-efficacy (Cancer Self-Efficacy Scale-Transplant), and coping (Measures of Current Status) at baseline and 30 and 60 days after HCT. We used mixed linear effect models to assess the effect of BMT-CARE on outcomes longitudinally. RESULTS: We enrolled 72.5% of eligible caregivers (100 of 138), and 80% attended 50% or more of the intervention sessions. Caregivers randomized to BMT-CARE reported improved QOL (B = 6.11; 95% CI, 3.50-8.71; P < .001), reduced caregiving burden (B = -6.02; 95% CI, -8.49 to -3.55; P < .001), lower anxiety (B = -2.18; 95% CI, -3.07 to -1.28; P < .001) and depression symptoms (B = -1.23; 95% CI, -1.92 to -0.54; P < .001), and improved self-efficacy (B = 7.22; 95% CI, 2.40-12.03; P = .003) and coping skills (B = 4.83; 95% CI, 3.04-6.94; P < .001) in comparison with the usual-care group. CONCLUSIONS: A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self-efficacy while reducing the caregiving burden during the acute HCT period.

RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress.

In the transition from B cells to Ab-secreting cells (ASCs) many genes are induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in abundance. Nonetheless, using splicing array technology and mouse splenic B cells plus or minus LPS, we found that induced and "uninduced" genes can show large differences in splicing patterns between the cell stages, which could influence ASC development. We found that ∼55% of these splicing changes depend on ELL2, a transcription elongation factor that influences expression levels and splicing patterns of ASC signature genes, genes in the cell-cycle and N-glycan biosynthesis and processing pathways, and the secretory versus membrane forms of the IgH mRNA. Some of these changes occur when ELL2 binds directly to the genes encoding those mRNAs, whereas some of the changes are indirect. To attempt to account for the changes that occur in RNA splicing before or without ELL2 induction, we examined the amount of the small nuclear RNA molecules and found that they were significantly decreased within 18 h of LPS stimulation and stayed low until 72 h. Correlating with this, at 18 h after LPS, endoplasmic reticulum stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1-dependent mRNA decay with 4u8C correlates with the reduction in small nuclear RNA and changes in the normal splicing patterns at 18 h. Thus, we conclude that the RNA splicing patterns in ASCs are shaped early by endoplasmic reticulum stress and Ire1 phosphorylation and later by ELL2 induction.

Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation.

BACKGROUND: Cognitive decline is a frequently cited concern among patients receiving hematopoietic cell transplantation (HCT), and patients often experience neurocognitive deficits (i.e., stable or worsening neurocognitive performance) throughout the transplant course. Deficits can be most severe during the acute transplant period (i.e., 90 days after transplantation), when patients also typically experience elevated systemic levels of inflammation. Previous studies have identified inflammation as a likely mechanism underlying neurocognitive deficits, primarily in women with breast cancer; however, longitudinal studies have been limited. In this study, our aim was to evaluate the relationship between changes in systemic inflammation and changes in cognition from pre- to post-transplant in patients receiving allogeneic HCT. METHODS: Patients scheduled for allogeneic HCT (n = 85) were assessed prior to HCT and 90 days after HCT. Biomarkers of inflammation included IL-6, sTNF-RII, CRP, and IL-1ra, which have been previously associated with neurocognitive deficits in cancer patients. Patients completed neuropsychological testing and self-report questionnaires. RESULTS: Mixed models demonstrated that from pre- to post-HCT, increases in IL-6 and sTNF-RII were associated with neurocognitive deficits, and decreases in CRP were associated with better neurocognitive performance. There were no significant associations between changes in inflammation and self-reported cognitive performance. CONCLUSIONS: Our findings are the first to our knowledge to report a robust relationship between increasing inflammation and neurocognitive deficits from pre- to post-HCT. Additional studies are needed to confirm these findings in a larger sample.

Illness perceptions predict health practices and mental health following hematopoietic stem cell transplantation.

OBJECTIVE: Beliefs about illness have been shown to shape health practices and coping efforts. The present study investigated illness perceptions among patients undergoing hematopoietic stem cell transplant (HSCT). We also examined the extent to which perceptions predicted health practices and mental health following transplant. METHODS: Participants (N = 332) completed measures of illness perceptions (beliefs about cancer consequences and course, personal and treatment control over cancer, and understanding of one's cancer) prior to HSCT. Health practices (diet, physical activity, and alcohol use) and mental health (depression, anxiety, and psychological well-being) were assessed pre transplant and at 1, 3, 6, and 12 months post transplant. RESULTS: On average, HSCT recipients felt they understood their cancer, viewed their cancer to be a chronic condition with severe consequences, and believed they had moderate personal control over their cancer but that medical treatment provided more control. Perceptions varied by transplant type. Mixed-effects linear regression models revealed that HSCT recipients who perceived the consequences of their cancer to be more serious experienced more depression and anxiety, less well-being, and ate a healthier diet, but were less physically active during the year following transplant. Those with greater personal and treatment control ate a healthier diet and reported greater well-being. Patients with a better understanding of their cancer also ate a healthier diet and reported less depression, less anxiety, and greater well-being. CONCLUSIONS: Perceptions of cancer shape HSCT recipients' health practices and psychological well-being during the critical first year of recovery after transplant.

Loneliness as a mediator of the relationship of social cognitive variables with depressive symptoms and quality of life in lung cancer patients beginning treatment.

OBJECTIVE: Loneliness, or the discrepancy between perceived and desired level of social connectedness, is an understudied but important psychosocial factor in cancer patients. The current study investigated the relationship between loneliness, depressive symptoms, quality of life, and social cognitive variables (eg, stigma, social constraint, and cancer-related negative social expectations), and explored loneliness as a mediator of the relationship between social cognitive variables and depressive symptoms and quality of life in lung cancer patients beginning treatment. METHODS: Patients within 3 months of beginning treatment for lung cancer completed measures of loneliness, depressive symptoms, quality of life, and social cognitive variables. Correlational, chi-square, and hierarchical regression analyses evaluated relationships among variables. Bias-corrected bootstrapping methods estimated the indirect effect and 95% confidence interval for mediation models. RESULTS: Participants (n = 105, M = 65.5 years, 55% female) endorsed low to moderate levels of loneliness. Greater loneliness was associated with greater depressive symptoms and worse quality of life (P's < .001), and loneliness explained unique variance in depressive symptoms (F = 10.18, P < .001, ΔR2  = .06, Total R2  = .35) and quality of life (F = 19.55, P < .001, ΔR2  = .05, Total R2  = .52) after controlling for significant covariates. Greater stigma, social constraint, and cancer-related negative social expectations were associated with greater loneliness and depressive symptoms and worse quality of life (P's < .001). Loneliness partially mediated the relationship of social cognitive variables with depressive symptoms and quality of life. CONCLUSIONS: Beyond its direct impact on clinically relevant outcomes, the experience of loneliness may be a mechanism by which social cognitive factors influence depressive symptoms and quality of life in lung cancer patients.

Systems Measures of a Trauma-Informed Approach: A Systematic Review.

Interest in trauma-informed approaches has grown substantially. These approaches are characterized by integrating understanding of trauma throughout a program, organization, or system to enhance the quality, effectiveness, and delivery of services provided to individuals and groups. However, variation in definitions of trauma-informed approaches, coupled with underdeveloped research on measurement, poses challenges for evaluating the effectiveness of models designed to support a trauma-informed approach. This systematic review of peer-reviewed and gray literature identified 49 systems-based measures that were created to assess the extent to which relational, organizational, and community/system practices were trauma-informed. Measures were included if they assessed at least one component of a trauma-informed approach, were not screening or diagnostic instruments, were standardized, were relevant to practices addressing the psychological impacts of trauma, were printed in English, and were published between 1988 and 2018. Most (77.6%) measures assessed organizational-level staff and climate characteristics. There remain several challenges to this emerging field, including inconsistently reported psychometric data, redundancy across measures, insufficient evidence of a link to stakeholder outcomes, and limited information about measurement development processes. We discuss these opportunities and challenges and their implications for future research and practice.

Effect of androgen deprivation therapy on sexual function and bother in men with prostate cancer: A controlled comparison.

OBJECTIVES: The adverse sexual effects of androgen deprivation therapy (ADT) on men with prostate cancer have been well described. Less well known is the relative degree of sexual dysfunction and bother associated with ADT compared to other primary treatment modalities such as radical prostatectomy. We sought to describe the trajectory and relative magnitude of changes in sexual function and bother in men on ADT and to examine demographic and clinical predictors of ADT's adverse sexual effects. METHODS: Prostate cancer patients treated with ADT (n = 60) completed assessments of sexual function and sexual bother 3 times during a 1-year period after the initiation of ADT. Prostate cancer patients treated with radical prostatectomy only and not receiving ADT (n = 85) and men with no history of cancer (n = 86) matched on age and education completed assessments at similar intervals. RESULTS: Androgen deprivation therapy recipients reported worsening sexual function and increasing bother over time compared to controls. Effect sizes for the differences in sexual function were large to very large, and for bother were small to very large. Age younger than 83 years predicted relatively poorer sexual function, and age younger than 78 years predicted greater sexual bother at 12 months in men on ADT compared to men not on ADT. CONCLUSIONS: Most men on ADT for prostate cancer will never return to baseline levels of sexual function. Interventions focused on sexual bother over function and designed to help couples build and maintain satisfying relationship intimacy are likely to more positively affect men's psychological well-being while on ADT than medical or sexual aids targeting sexual dysfunction.