The health risk of social disadvantage is transplantable into a new host.

Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival (P = 0.001) and 6.6% increase in treatment-related mortality within 3 y (P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients.

Weathering the storm when the end of the road is near: A qualitative analysis of supportive care needs during CAR T-cell therapy in pediatrics.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied. METHODS: English- or Spanish-speaking patients (ages 8-25 years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3 months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis. RESULTS: Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5 years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity. CONCLUSIONS: Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns.

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities.

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Perceptions and Current Practices in Patient-Centered Care: A Qualitative Study of Ryan White HIV Providers in South Florida.

Background: Patient-centered care (PCC) improves HIV adherence and retention, though lack of consensus on its conceptualization and understanding how it is interpreted has hindered implementation. Methods: We recruited 20 HIV providers at Ryan White Programs in FL for in-depth interviews. Thematic analysis identified core consistencies pertaining to: 1) provider perceptions, 2) current practices promoting PCC. Results: Provider perceptions of PCC emerged under four domains: 1) holistic, 2) individualized care, 3) respect for comfort and security, and 4) patient engagement and partnership. PCC practices occurred at multiple levels: 1) individual psychosocial and logistical support, 2) interpersonal support within patient-provider relationships through respectful communication and active engagement, and 3) institutional practices including feedback mechanisms, service integration, patient convenience, and diverse staffing. Conclusions: Our findings highlight the central tenets of PCC as respectful, holistic, individualized, and engaging care. We offer an HIV-adapted framework of PCC as a multilevel construct to guide future intervention.

Patient-centered care perspectives among HIV care providersThis study explores HIV care provider perceptions of patient-centered care (PCC) by analyzing common themes that arose in interviews. We found that providers perceived PCC to be holistic, individualized care focused on respecting patient comfort and security and actively engaging them as partners in care. Providers discussed a variety of ways in which they practiced PCC at the individual service level through psychosocial and logistical support, through their interpersonal relationships with respectful communication and trust, and through more structured facility level policies and activities such as greater service integration and employing a diverse staff. PCC is rapidly becoming the new standard of care and this study hopes to offer insight into provider perceptions of PCC and examples of practice in the HIV care field.

Understanding motivations and resilience-associated factors to promote timely linkage to HIV care: a qualitative study among people living with HIV in western Kenya.

Understanding motivations and resilience-associated factors that help people newly diagnosed with HIV link to care is critical in the context of universal test and treat. We analyzed 30 in-depth interviews (IDI) among adults aged 18 and older in western Kenya diagnosed with HIV during home-based counseling and testing and who had linked to HIV care. A directed content analysis was performed, categorizing IDI quotations into a table based on linkage stages for organization and then developing and applying codes from self-determination theory and the concept of resilience. Autonomous motivations, including internalized concerns for one's health and/or to provide care for family, were salient facilitators of accessing care. Controlled forms of motivation, such as fear or external pressure, were less salient. Social support was an important resilience-associated factor fostering linkage. HIV testing and counseling programs which incorporate motivational interviewing that emphasizes motivations related to one's health or family combined with a social support/navigator approach, may promote timely linkage to care.

Experiences of racial discrimination and adverse gene expression among black individuals in a level 1 trauma center sample.

Up to 40 % of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and six-months (T2) post-injury, Black participants (N = 94) provided a blood specimen and completed assessments of lifetime racial discrimination and PTSD symptoms. Mixed effect linear models evaluated the relationship between change in CTRA gene expression and racial discrimination while adjusting for age, gender, body mass index (BMI), smoking history, heavy alcohol use history, and trauma-related variables (mechanism of injury, lifetime trauma). Results revealed that for individuals exposed to higher levels of lifetime racial discrimination, CTRA significantly increased between T1 and T2. Conversely, CTRA did not increase significantly over time in individuals exposed to lower levels of lifetime racial discrimination. Thus, racial discrimination appeared to lead to a more sensitized biological profile which was further amplified by the effects of a recent traumatic injury. These findings replicate and extend previous research elucidating the processes by which racial discrimination targets biological systems.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Racial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis.

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.

Prevalence of Sleep Aid Medication Use in Patients Receiving a Hematopoietic Cell Transplant on an Inpatient Unit.

BACKGROUND AND OBJECTIVES: There is a lack of research regarding the use of sleep aids after hematopoietic stem cell transplantation (HCT). We describe the prevalence of sleep aid administration in the HCT unit and identify associations with patient or clinical characteristics. PATIENTS AND METHODS: In this retrospective analysis of sequential inpatient HCTs from July 1 to December 31, 2016 we describe whether and when patients were prescribed sleep aid medications. Chi-square tests determined significant differences between patient characteristics, sleep aid prescription, and time of prescription. RESULTS: Of the 225 patients identified, 193 (86%) were prescribed sleep aids. Significantly more women received prescriptions for sleep aids (90.4%) than men (81%; P = .047). One hundred patients (44%) received prescriptions exclusively while in the hospital. CONCLUSION: Findings show a high prevalence of sleep medication use in patients undergoing inpatient HCT, primarily during hospitalization. Future efforts toward standardized recommendations to optimize peri-transplant sleep would help clinicians and patients.

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.

Mobile health (mHealth) interventions in prostate cancer survivorship: a scoping review.

PURPOSE: This scoping review explores the application of mHealth technology in prostate cancer (CaP) management along the survivorship continuum. METHODS: The scoping review was conducted using the five-step framework developed by Arksey and O'Malley. Using predefined criteria, we screened citations from Embase, EBSCOHost, Cochrane Library, PubMed, ProQuest, SCOPUS, and Web of Science for primary studies published before December 2021. We selected studies that explored the application of mHealth technology in CaP management and survivorship. Evidence from 14 eligible studies was summarized using narrative synthesis. RESULTS: Fourteen studies published between 2015 and 2021 were included. Ten mHealth apps were identified with only one still in use. Most apps were explored for their supportive care roles during radiotherapy (n = 9) and androgen deprivation therapy (ADT) (n = 1) treatment, mainly to assess outcomes (n = 1) and manage patient-reported symptoms (n = 5). One study deployed mHealth to facilitate recovery after surgery. Very few studies (n = 3) applied mHealth for lifestyle management (i.e., physical activity). Barriers to app usage included connectivity issues, end-user familiarity with the app, login hurdles, and time constraints. Facilitators of app usage included apps being downloaded for participants, devices provided for participants, and the ability to connect with providers through the platform. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: The improving survival rates from CaP suggest that men are now living longer with unfavorable treatment side effects such as reduced sexual functioning, pain, and fatigue. Hence, mHealth represents new hope in men's illness trajectory. However, current application in patients' care pathways remains poor, particularly in the active phase of CaP management. Efforts must be accelerated to explore individual and healthcare-level drivers of mHealth use. The feasibility and descriptive nature of current studies point to a lack of attention to actual implementation and scale-up issues in research considering mHealth application in CaP, hence accounting partly for the gap in research/practice.

The Impact of Beta-Blocker Use at the Time of Hematopoietic Cell Transplantation on the Development of Acute and Chronic Graft-Versus-Host Disease.

Sympathetic nervous system activation plays a role in the development of acute and chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT). The primary objective was to compare the cause-specific hazard of grade II-IV and III-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) in the context of ß-blocker use and type (selective vs. non-selective). Secondary objectives included overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse, non-relapse mortality (NRM), and grade II-IV and III-IV aGVHD and cGVHD. The current study included 151 patients ages 18 and older diagnosed with hematological malignancies who underwent reduced intensity conditioning allogeneic HCT from HLA matched related or unrelated donors between January 2014 and 2017. 31 patients were on a ß-blocker of which 71% were on a selective ß-blocker. The incidence of aGVHD was not different among groups. Results show a non-significant trend in the association between ß-blocker use and reduction in the risk of developing cGVHD (cause-specific hazard ratio 0.49, p = 0.060), with no negative impact on survival or relapse. The current data are supportive of a potential ß-adrenergic influence on the pathogenesis of GVHD, consistent with the inflammatory etiology of GVHD and the anti-inflammatory effects of ß-adrenergic antagonists.

Abrupt onset of severe parkinsonism in a patient with metastatic gastrointestinal stromal tumor receiving treatment with avapritinib: A case report.

Gastrointestinal stromal tumors (GISTs) are tumors of the digestive tract. To date, there have been no neurological paraneoplastic syndromes or symptoms associated with metastatic GISTs. Tyrosine kinase inhibitors (TKIs) are the typical class of agents used in management of this malignancy. Avapritinib, a new TKI, has been associated with myriad neurological adverse events with fairly rapid resolution in clinical trials. Herein, we present the case of a patient with metastatic GIST who, after starting treatment with avapritinib, developed rapidly progressive and persisting severe neuropsychiatric symptoms, including profound parkinsonism and encephalopathy, while concurrently receiving therapy with the antipsychotic olanzapine. We posit that the patient could be conceptualized as having a relative vulnerability to medication effects in the setting of metastatic GIST - possibly driven by an immune-mediated process - and that the addition of avapritinib triggered an overtly evident, clinically significant cascade of neurological deterioration.

Biobehavioral Implications of Chimeric Antigen Receptor T-cell Therapy: Current State and Future Directions.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable clinical responses in hematologic malignancies. Recent advances in CAR T-cell therapy have expanded its application into other populations including older patients and those with central nervous system and solid tumors. Although its clinical efficacy has been excellent for some malignancies, CAR T-cell therapy is associated with severe and even life-threatening immune-mediated toxicities, including cytokine release syndrome and neurotoxicity. There is a strong body of scientific evidence highlighting the connection between immune activation and neurocognitive and psychological phenomena. To date, there has been limited investigation into this relationship in the context of immunotherapy. In this review, we present a biobehavioral framework to inform current and future cellular therapy research and contribute to improving the multidimensional outcomes of patients receiving CAR T-cell therapy.

Targeting the ß2 -adrenergic receptor increases chemosensitivity in multiple myeloma by induction of apoptosis and modulating cancer cell metabolism.

While multi-drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used for other indications could provide a novel approach to improve the therapeutic efficacy of standard multiple myeloma treatments. Here, we assessed the anti-tumor effects of cardiac drugs called ß-blockers as a single agent and in combination with commonly used anti-myeloma therapies. Expression of the ß2 -adrenergic receptor correlated with poor survival outcomes in patients with multiple myeloma. Targeting the ß2 -adrenergic receptor (ß2 AR) using either selective or non-selective ß-blockers reduced multiple myeloma cell viability, and induced apoptosis and autophagy. Blockade of the ß2 AR modulated cancer cell metabolism by reducing the mitochondrial respiration as well as the glycolytic activity. These effects were not observed by blockade of ß1 -adrenergic receptors. Combining ß2 AR blockade with the chemotherapy drug melphalan or the proteasome inhibitor bortezomib significantly increased apoptosis in multiple myeloma cells. These data identify the therapeutic potential of ß2 AR-blockers as a complementary or additive approach in multiple myeloma treatment and support the future clinical evaluation of non-selective ß-blockers in a randomized controlled trial. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

New-onset hallucinations with amiodarone: a case report.

BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature. CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12 years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11 years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3 days after the discontinuation of amiodarone. CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.

Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients.

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.

The effect of tocilizumab on patient reported outcomes and inflammatory biomarkers in hematopoietic cell transplantation.

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach. We conducted an observational cohort study to explore patient reported outcomes (PROs) and inflammatory biomarkers among allogeneic HCT recipients who received tocilizumab compared to those who did not. Individuals on a larger trial of tocilizumab for prevention of graft-versus-host disease received a single dose of tocilizumab 24 h prior to stem cell infusion. Measures of anxiety, depression, pain, fatigue, and sleep quality and parallel blood samples for inflammatory cytokines were collected from participants and an analogous comparison cohort at baseline and Day 28 after stem cell infusion. Demographic and medical characteristics were reported; an analysis of covariance regression model was fitted to evaluate differences in PROs and distance correlation t-tests assessed for associations between biomarkers and PRO measures. For n = 18 tocilizumab-treated and n = 22 comparison patients, there were no significant differences between patient demographics, but the tocilizumab cohort had a different distribution of primary diagnoses (p = 0.009) with more patients with leukemias and a higher proportion of patients in their first remission (64% vs 28%, p = 0.024). Depression was higher at Day 28 compared to baseline in both groups (comparison group: +5.1 [95% CI 0.14-10, p = 0.045], tocilizumab: +8.6 [95% CI 2.3-15, p = 0.011]), though the difference between groups did not reach statistical significance. The tocilizumab group had significantly increased circulating IL-6 and decreased CRP at Day 28 (all p < 0.05). There was an association between collective baseline biomarkers and PROs (distance correlation dCor = 0.110, p = 0.005), but this same association was not present at Day 28 (dCor = -0.001, p = 0.5). In univariate analyses, a 10-fold increase in plasma IL-6 was associated with a 3.6-point higher depression score (95% CI 1.0-6.2, p = 0.008). In this exploratory analysis of PROs and inflammatory biomarkers in patients undergoing HCT, tocilizumab was not associated with favorable patient-reported symptom profiles. This finding is aligned with our prior work in the HCT population but diverges from hypothesized therapeutic effects of tocilizumab on depressive symptoms, thus highlighting the need for larger prospective translational studies in biobehavioral HCT research.