Jennifer M Knight

Medical College of Wisconsin | MCW · Department of Psychiatry and Behavioral Medicine

There has been an increase in volume as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have impacted racial/ethnic minorities equally. In this observational study from Center for International Blood and Marrow Transplant Research of 79,904 autolog...

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOH), which can affect health outcomes through the stress response pathway. The Conserved Transcriptional Response to Adversity (CTRA) is a stress-mediated pro-inflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) ou...

6500 Background: Allogeneic hematopoietic cell transplantation (HCT) carries significant risks, with low socioeconomic status (SES) being predictive of increased mortality. Our team recently discovered that socioeconomic disadvantage among unrelated HCT donors results in decreased recipient overall survival (OS) and increased treatment-related mort...

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...

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 ne...

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 cardi...

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...

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 pande...

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 un...

The relationship between psychosocial factors and cancer has intrigued people for centuries. In the last several decades there has been an expansion of mechanistic research that has revealed insights regarding how stress activates neuroendocrine stress-response systems to impact cancer progression. Here, we review emerging mechanistic findings on k...

Background With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment’s impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects. Methods The purpose of this exploratory study was to assess short-term...

Successful hematopoietic cell transplantation (HCT) depends on rapid engraftment of the progenitor and stem cells that will reestablish hematopoiesis. Rap1A and Rap1B are two closely related small GTPases that may affect platelet and neutrophil engraftment during HCT through their roles in cell adhesion and migration. β-adrenergic signaling may reg...

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 i...

Background Socioeconomic Status (SES) is recognized as a major contributor to health disparities in overall disease rate, morbidity, mortality, and quality of life (QOL). Specifically, low SES, independent of race, has a negative impact on solid and haematological cancer outcomes. Chimeric antigen receptor (CAR) T-cell cancer therapy is an increasi...

Introduction: CAR-T cell therapy is associated with extra-ordinary costs with estimates of as much as $1.5 million in some patients, including the high list-price for the CAR-T product, additional costs of inpatient stay, toxicity management and outpatient follow-up. As a result, CAR-T therapy may be associated with financial toxicity for patients...

Introduction: Hematopoietic cell transplantation (HCT) carries significant risks for mortality, which are not proportionally shared across individuals. Among HCT recipients, we have previously shown that low socioeconomic status (SES) is predictive of increased mortality following HCT, and the underlying mechanism for this outcome is not fully expl...

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). 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 an...

Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma c...

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes – defined here as the interactions of behavioral, psychol...

Objective Distress and depression are prevalent in cancer patients throughout survivorship and are associated with adverse outcomes. This study examines the association between outpatient psycho‐oncology treatment and distress and depression in cancer patients. Methods This is a prospective observational study of adult patients with a primary diag...

Because medical illness is associated with increased inflammation and an increased risk for treatment-resistant major depressive disorder, anti-cytokine therapy may represent a novel, and especially efficacious, treatment for depression. We hypothesized that blockade of the interleukin (IL)-6 signaling pathway with tocilizumab would decrease depres...

Fear of cancer recurrence (FoR) is an important yet underestimated long term sequela that many cancer survivors suffer from. The continuous state of uncertainty the survivors might go through can lead to a serious impact on their quality of life (QoL), which is collectively referred to as Damocles syndrome. Given the increasing numbers of cancer su...

Introduction Chimeric antigen receptor (CAR) T cell immunotherapy represents a novel and increasingly used treatment modality for patients with relapsed and/or refractory B cell malignancies. Acute neurological toxicities of CAR-T cell therapy (e.g. immune effector cell-associated neurotoxicity syndrome) are well described, though delayed cognitive...

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital...

Fatigue is a commonly reported quality of life concern after hematopoietic stem cell transplant (HSCT). Fatigue severity, duration, and interference with daily activities were evaluated at post-transplant milestones during acute recovery and through 6 years post-HSCT. We also investigated whether disease and treatment factors (allogeneic or autolog...

Preclinical research shows that stress-induced activation of the sympathetic nervous system can promote hematopoietic malignancies via β-adrenoreceptor–mediated molecular pathways. Hematopoietic cell transplant (HCT) recipients exposed to conditions of chronic stress show activation of a conserved transcriptional response to adversity (CTRA) gene e...

Background: Clinical outcomes among allogeneic hematopoietic cell transplant (HCT) recipients are negatively affected by low socioeconomic status (SES), yet the biological mechanisms accounting for this health disparity remain to be elucidated. Among unrelated donor HCT recipients with acute myelogenous leukemia, one recent pilot study linked low...

Allogeneic hematopoietic cell transplantation (alloHCT) is offered in a limited number of medical centers and is associated with significant direct and indirect costs. The degree to which social and geographic barriers reduce access to alloHCT is unknown. Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for Int...

Introduction Hematopoietic stem cell transplantation (HCT) produces pro-inflammatory cytokines including IL-6 which can activate central nervous system (CNS) pathways to cause depressed mood, anxiety, fatigue, and sleep disturbance. Tocilizumab (toci), an IL-6 receptor antagonist, is an FDA approved treatment for cytokine release syndrome (CRS), a...

Beta-adrenergic signaling regulates multiple molecular pathways that contribute to cancer progression; beta-adrenergic antagonists efficiently block many of these effects in animals. We previously demonstrated that hematopoietic cell transplant (HCT) patients exposed to socioeconomic stress show activation of a conserved transcriptional response to...

Sickness symptoms associated with immunomodulatory treatments for cancer provided some of the first evidence for the neural and behavioral actions of cytokines. We now see a reemergence of this clinical relevance in the context of new therapeutic modalities targeting different aspects of immunity, including the IL-6 receptor antagonist tocilizumab....

Historically, sickness symptomatology in cancer patients has been studied as aggregated phenomena arising from a similar inflammatory etiology. A parent clinical trial analyzed depression, anxiety, fatigue, sleep, and pain as separate variables in hematopoietic cell transplant (HCT) recipients experiencing cytokine blockade with an interleukin-6 re...

Objective The purpose of the current study was to (1) assess healthcare providers’ beliefs about and referral patterns to yoga and meditation services, and (2) evaluate the effectiveness of a brief yoga/meditation educational presentation to increase providers’ intent to recommend these programs. Method A brief 5-min presentation regarding the ben...

Sleep disruption has received little attention in hematopoietic cell transplantation (HCT). The goal of this study was to describe severity, course, and predictors of sleep disruption following HCT. A secondary data analysis was conducted of the Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) 0902 study. Participants completed a...

Graft versus host disease (GVHD) is a frequent cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD occurs when donor lymphocytes are activated by inflammatory cytokines and alloantigens. The role of donor biological characteristics, such as basal inflammation, has not been investigated as a risk...

Background Repurposing existing medications for antineoplastic purposes can provide a safe, cost-effective, and efficacious means to further augment available cancer care. Clinical and preclinical studies suggest a role for the ß-adrenergic antagonist (ß-blocker) propranolol in reducing rates of tumor progression in both solid and hematologic malig...

Background: For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions upon post-transplant outcomes is n...

Randomized controlled trials (RCTs) incorporating basic science psychoneuroimmunology (PNI) mechanisms into translatable clinical findings are critical to implementing PNI discoveries into standard medical practice. Biobehavioral pathways involving stress-induced beta-adrenergic signaling are implicated in tumor progression, with beta-blockers demo...

Graft-versus-host disease (GVHD) induces pathological damage in peripheral target organs leading to well-characterized, organ-specific clinical manifestations. Patients with GVHD, however, can also have behavioral alterations that affect overall cognitive function, but the extent to which GVHD alters inflammatory and biochemical pathways in the bra...

Background: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes posttransplantation. Methods: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adul...

BACKGROUND Routine monitoring of cancer‐related distress is recognized as essential to quality care and mandated by a major accrediting organization. However, to the authors' knowledge, few cancer‐specific measures have been developed to date to assess the multiple cancer‐related factors contributing to this distress. In the current study, the auth...

Psychosocial and socioeconomic factors have predicted morbidity and mortality following hematopoietic cell transplantation (HCT). However, previous studies suffer from methodological limitations, and few investigate biobehavioral pathways. This multi-center study assessed whether pre-HCT psychosocial and socioeconomic measures are associated with e...

Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0902 evaluated whether exercise and stress management training prior to hematopoietic cell transplantation (HCT) improved physical and mental functioning after HCT. Neither overall survival nor other patient-reported transplant outcomes were improved by the training intervention...

This secondary analysis of a large, multi-center Blood and Marrow Transplant Clinical Trials Network (BMT CTN) randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes including time to hem...

Quality of life is increasingly recognized as an important secondary endpoint of hematopoietic cell transplantation (HCT). The current study examined the extent to which attrition results in biased estimates of patient quality of life. The study also examined whether patients differ in terms of trajectories of quality of life in the first six month...

Introduction: Depression is associated with increased mortality among healthy individuals and patients with various medical conditions including cardiovascular disease and cancer. The impact of an existing diagnosis of depression prior to autologous and allogeneic hematopoietic stem cell transplantation (HCT) on clinical outcomes including overall...

Background: In hematopoietic cell transplantation (HCT), current risk adjustment strategies are based on clinical and disease-related variables. Although patient-reported outcomes (PROs) predict mortality in multiple cancers, they have been less well studied within HCT. Improvements in risk adjustment strategies in HCT would inform patient selecti...

Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile know...

Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the...

Objective Multiple psychosocial factors appear to affect cancer progression in various populations; however, research investigating the relationship between psychosocial factors and outcomes following hematopoietic stem cell transplantation (HCT) is scarce. Subject to adverse immunological and psychological conditions, HCT patients may be especiall...

The endocannabinoid system modulates neural processes and down-regulates pro-inflammatory, stress-related signals. Inflammatory-mediated processes significantly contribute to increased morbidity and mortality in hematopoietic stem cell transplantation (HCT). The relationship between inflammatory molecules and the endocannabinoid system is poorly un...

While psychosocial factors are known to affect cancer progression via biobehavioral pathways in many patient populations, these relationships remain largely unexplored in hematopoietic stem cell transplant (HCT) patients. The purpose of this paper is to critically review the literature regarding psychosocial and endocrine/immune aspects of HCT, wit...

Objectives: The objectives of this study were to examine the effects of specific Mindfulness-Based Stress Reduction (MBSR) activities (yoga, sitting and informal meditation, body scan) on immune function, circulating insulin-like growth factor (IGF)-1 concentrations, and positive affect among older adults. Design: The study design comprised long...

To determine whether there is a relationship between depressive symptoms and cortisol assessed at first morning awakening, 6 PM, and 9 PM in a population-based sample of midlife women. If this relationship is not linear, we aim to test whether this relationship is nonlinear, only present in those with more severe depressive symptoms, better account...