Cognition in patients treated with targeted therapy for chronic myeloid leukemia: a controlled comparison.

This controlled comparison study evaluated objective and subjective cognitive function and their relationships with patient-reported symptoms (depression, fatigue, insomnia) in patients receiving tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and non-cancer controls. Patients with CML in chronic phase treated with the same oral TKI for ≥6 months (n = 90) and non-cancer controls (n = 87) completed a neurocognitive battery and self-report measures. Patients demonstrated worse overall neuropsychological performance (p = .05) and verbal memory (p = .02) compared to controls. Patients were not more likely to meet criteria for impaired cognitive performance compared to controls (ps>.26). Patients reported worse subjective global and domain-specific cognitive complaints and less satisfaction with cognitive function compared to controls (ps < .05). Patients also reported greater fatigue and insomnia symptoms (ps < .001). In both groups, greater fatigue, insomnia, and depressive symptoms were associated with worse subjective cognition (ps < .01). Longitudinal studies are needed to examine changes in cognitive function in patients before and during TKI treatment.

Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. This study examined changes in cognition in the first year after CD19-directed CAR T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.g., ICANS, CRS) and nonspecific risk factors (e.g., baseline quality of life, frailty) for worsening cognition. Patients' perceived cognition was assessed at baseline and at days 90 and 360. Clinical variables were abstracted from medical records. Piecewise mixed models were used to examine acute change (i.e., within 90 days) and longer-term change (i.e., from 90 days to 360 days) in cognition, as well as to explore risk factors for worsening cognition. Among 118 participants (mean age 61, 59% male), mean levels of perceived cognition did not change from baseline to day 90 (P> .05) but worsened from day 90 to day 360 in global cognition and in the domains of memory, language, organization, and divided attention (P< .05). Although statistically significant, changes were small (d values 0.15-0.28). Greater baseline fatigue, anxiety, and depression were associated with worse global cognition at day 90 (P< .01). Patients with more severe ICANS post-CART reported worse global cognition at day 360 (P< .05), although there were no differences in perceived cognition by severity of CRS (P> .05). Other putative risk factors were not associated with acute or longer-term changes in perceived cognition (P> .05). CAR T-cell therapy recipients reported delayed deterioration in several cognitive domains, although changes were small. These findings may be useful when educating future patients on what to expect when receiving CAR T-cell therapy.

Change in Neurocognitive Performance Among Patients with Non-Hodgkin Lymphoma in the First Year after Chimeric Antigen Receptor T Cell Therapy.

The success of chimeric antigen receptor (CAR) T cell therapy in treating patients with relapsed/refractory hematologic malignancies is leading to a growing number of survivors treated with this regimen. To our knowledge, no previous studies have examined neurocognitive performance in adult CAR T cell therapy recipients, despite high rates of neurotoxicity and cytokine release syndrome (CRS) in the acute treatment period. This study examined changes in neurocognitive performance in the first year after CAR T cell therapy for non-Hodgkin lymphoma (NHL). Putative risk factors for worsening neurocognitive performance (eg, neurotoxicity, CRS) were explored as well. Neurocognition was assessed before initiation of CAR T cell therapy and at 30, 90, and 360 days post-treatment. Clinical variables were abstracted from medical records. Mixed models were used to examine change in total neurocognitive performance (TNP) and cognitive domains (ie, attention, executive function, verbal ability, immediate and delayed memory, and visuospatial abilities). Among 117 participants (mean age, 61 years; 62% male), TNP and executive function declined slightly on average from baseline to day 90 and then improved from day 90 to day 360 (P < .04). Small but significant linear declines in visuospatial ability on average were also observed over time (P = .03). Patients who had 4 or more lines of previous therapy and those with worse neurotoxicity (but not CRS) demonstrated worse TNP. CAR T cell therapy recipients reported transient or persistent deterioration in several cognitive domains, although changes were slight. These findings may be useful when educating future patients on what to expect when receiving CAR T cell therapy.

Quality of life in caregivers of patients receiving chimeric antigen receptor T-cell therapy.

OBJECTIVE: Informal family caregivers provide critical support for patients receiving chimeric antigen receptor (CAR) T-cell therapy. However, caregivers' experiences are largely unstudied. This study examined quality of life (QOL; physical functioning, pain, fatigue, anxiety, and depression), caregiving burden, and treatment-related distress in caregivers in the first 6 months after CAR T-cell therapy, when caregivers were expected to be most involved in providing care. Relationships between patients' clinical course and caregiver outcomes were also explored. METHODS: Caregivers completed measures examining QOL and burden before patients' CAR T-cell therapy and at days 90 and 180. Treatment-related distress was assessed at days 90 and 180. Patients' clinical variables were extracted from medical charts. Change in outcomes was assessed using means and 99% confidence intervals. Association of change in outcomes with patient clinical variables was assessed with backward elimination analysis. RESULTS: A total of 99 caregivers (mean age 59, 73% female) provided data. Regarding QOL, pain was significantly higher than population norms at baseline but improved by day 180 (p < .01). Conversely, anxiety worsened over time (p < .01). Caregiver burden and treatment-related distress did not change over time. Worsening caregiver depression by day 180 was associated with lower patient baseline performance status (p < .01). Worse caregiver treatment-related distress at day 180 was associated with lower performance status, intensive care unit admission, and lack of disease response at day 90 (ps < 0.01). CONCLUSIONS: Some CAR T-cell therapy caregivers experience pain, anxiety, and burden, which may be associated patients' health status. Further research is warranted regarding the experience of CAR T-cell therapy caregivers.

Acute patient-reported outcomes in B-cell malignancies treated with axicabtagene ciloleucel.

Chimeric antigen receptor T-cell therapy with axicabtagene ciloleucel (axi-cel) has considerably improved survival in adults with relapsed/refractory large B-cell lymphoma. This study reports patient-reported outcomes (PROs) such as quality of life (QOL) and toxicity in the first 90 days after treatment. Hematologic cancer patients treated with axi-cel (N = 103, mean age = 61, 39% female) completed SF-36 or PROMIS-29 QOL questionnaires prior to treatment and 90 days after. PRO-Common Terminology Criteria for Adverse Events toxicity items were completed by patients at baseline and 14, 30, 60, and 90 days after treatment. Mixed models examined change in PROs over time. From preinfusion to 90 days later, patients reported improvements in physical functioning, pain, and fatigue (ps < 0.01), but worsening of anxiety (p = 0.02). Patient-reported toxicities worsened by day 14 with improvement thereafter. The five most severe symptoms at day 14 included fatigue, decreased appetite, dry mouth, diarrhea frequency, and problems with concentration. Results indicate improvement in some domains of QOL over time with transient patient-reported toxicities.

COVID-19 pandemic causing medical and public health ethical dilemmas: A case report and review of literature.

The COVID-19 pandemic presented myriad of unprecedented and daunting ethical dilemmas to healthcare workers, patients, their families, and the public health. Here we present a case of a 42-years-old Hispanic female with underlying hematological malignancy that developed severe SARS-COV-2 infection amidst the pandemic. This case illustrates some remarkable ethical dilemmas during pandemic times, including the lack of advanced directive planning, the repercussions of restricting family visits, and what ethics in crisis and moral injury entails. Identifying the ethical challenges emerging from the pandemic will assist physicians and other providers in making proper decisions and maintaining the best standard of care.

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.

The Role of Age in Neurocognitive Functioning among Adult Allogeneic Hematopoietic Cell Transplant Recipients.

Improvements in supportive care have enabled allogeneic hematopoietic cell transplantation (HCT) to be performed in increasingly older patients. HCT is associated with neurocognitive impairment, which may be exacerbated in older adults due to normal neurocognitive decline associated with aging. The goal of this study was to evaluate whether increasing age of allogeneic HCT recipients is associated with worse neurocognitive outcomes over time relative to a matched sample of individuals without cancer. Patients (n = 140; 42% female; M age, 51 years; range, 20 to 76 years; 31% with acute myelogenous leukemia) completed neurocognitive assessments before transplantation and 3 months and 1 year after transplantation. Controls (n = 75; 56% female; M age, 53 years; range, 21 to 74 years) completed assessments at comparable time intervals. Linear mixed models revealed that regardless of age, patients demonstrated worse performance than controls before transplantation in verbal memory, visual memory, and total neuropsychological performance, and over time in executive functioning. In addition, older age was associated with worse performance in verbal memory (P = .02) and verbal fluency (P = .05) over time in patients compared with controls. Specifically, older (65+ years) patients had worse verbal memory and verbal fluency than older and younger (<65 years) controls post-transplantation (Cohen's d = .22 to .39). These data indicate that age may be a risk factor for worse neurocognitive outcomes after allogeneic HCT. If replicated, our results suggest that older candidates for allogeneic HCT should be counseled regarding the risk of cognitive problems after transplantation.

Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison.

PURPOSE: Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance. PATIENTS AND METHODS: Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations. RESULTS: ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001). CONCLUSION: Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.

Preservation of neurocognitive function and local control of 1 to 3 brain metastases treated with surgery and carmustine wafers.

BACKGROUND: Neurosurgical resection and whole-brain radiation therapy (WBRT) are accepted treatments for single and oligometastatic cancer to the brain. To avoid the decline in neurocognitive function (NCF) linked to WBRT, the authors conducted a prospective, multicenter, phase 2 study to determine whether surgery and carmustine wafers (CW), while deferring WBRT, could preserve NCF and achieve local control (LC). METHODS: NCF and LC were measured in 59 patients who underwent resection and received CW for a single (83%) or dominant (oligometastatic, 2 to 3 lesions) metastasis and received stereotactic radiosurgery (SRS) for tiny nodules not treated with resection plus CW. Preservation of NCF was defined as an improvement or a decline ≤ 1 standard deviation from baseline in 3 domains: memory, executive function, and fine motor skills, evaluated at 2-month intervals. RESULTS: Significant improvements in executive function and memory occurred throughout the 1-year follow-up. Preservation or improvement of NCF occurred in all 3 domains for the majority of patients at each of the 2-month intervals. NCF declined in only 1 patient. The chemowafers were well tolerated, and serious adverse events were reversible. There was local recurrence in 28% of the patients at 1-year follow-up. CONCLUSIONS: Patients with brain metastases had improvements in their cognitive trajectory, especially memory and executive function, after treatment with resection plus CW. The rate of LC (78%) was comparable to historic rates of surgery with WBRT and superior to reports of WBRT alone. For patients who undergo resection for symptomatic or large-volume metastasis or for tissue diagnosis, the addition of CW can be considered as an option.

Granulocyte Macrophage Colony Stimulating Factor Treatment is Associated with Improved Cognition in Cancer Patients.

BACKGROUND: Endogenous Granulocyte Macrophage Colony Stimulating Factor (GMCSF) is released in rheumatoid arthritis patients, who are largely protected from Alzheimer's disease (AD). Introducing exogenous GMCSF into an AD mouse model reduced amyloid deposition by 55% and restored normal cognition. No published studies have examined exogenous GMCSF and cognitive functioning in humans. OBJECTIVES/DESIGN: The goal of the current study was to examine the association between receipt of GMCSF and cognitive functioning in patients receiving colony stimulating factors as part of routine supportive care for hematopoietic cell transplantation (HCT). SETTING AND PARTICIPANTS: Archived neuropsychological data were examined from a longitudinal study of cognitive functioning in 95 patients receiving HCT at the Moffitt Cancer Center. INTERVENTION: Receipt of GMCSF and/or Granulocyte Colony Stimulating Factor (GCSF) was ascertained through patient billing records. MEASUREMENTS: Patients were assessed with a battery of neuropsychological tests prior to transplant and 6 and 12 months post-transplant. RESULTS: Patients treated with GMCSF and GCSF (n=19) showed significantly greater improvement in total neuropsychological functioning (TNP) at 6 months than patients treated with GCSF only (n=76) (p=.04). There was no group difference in TNP at 12 months (p=.24). Improvement in TNP from baseline to 6 months post-HCT was significant in the GMCSF+GCSF group (p=.01) but not the GCSF only group (p=.33). Improvement in TNP from baseline to 12 months post-HCT was significant in both groups (ps<.01). CONCLUSION: Preliminary data from this study of humans receiving colony stimulating factors suggest that receipt of GMCSF+GCSF was associated with greater cognitive improvement than GCSF alone. Randomized controlled trials of the effects of GMCSF on cognitive functioning in humans are warranted and underway to confirm these findings.

Clinical predictors of cognitive function in adults treated with hematopoietic cell transplantation.

BACKGROUND: Studies suggest that patients with cancer who undergo hematopoietic cell transplantation (HCT) are at risk for cognitive deficits. To date, little research has investigated the cumulative effects of clinical risk factors on cognitive function in patients who undergo HCT. METHODS: Patients (N = 278) who were scheduled to undergo HCT for hematologic disease completed neuropsychological assessments before HCT and at 6 months and 12 months after HCT. A time-varying cumulative clinical risk variable was examined as a predictor of total neuropsychological performance (TNP). Cumulative clinical risk was calculated from pre-HCT neuropsychological risk factors (eg, history of cranial irradiation, intrathecal chemotherapy), HCT-related risk factors (eg, allogeneic transplantation, unrelated donor), and post-HCT complications (eg, severity of mucositis and enteritis, graft-versus-host disease). RESULTS: Patients with greater cumulative clinical risk displayed worse TNP at baseline and at 6 months after HCT and less neuropsychological recovery over time than patients who had less risk (Ps < .05). Greater cumulative clinical risk predicted worse performance on tasks assessing executive function at baseline and 6 months after HCT and assessing memory at 6 months and 12 months after HCT (Ps < .05). Among risk variables, length of hospital stay was the only significant predictor of neuropsychological function (P < .05). CONCLUSIONS: Findings from this study indicated that clinical risk factors may have a cumulative effect on cognitive function in patients who undergo HCT. Patients who have a complicated clinical course should be referred for evaluation and management of cognitive deficits.

Do coping and social support predict depression and anxiety in patients undergoing hematopoietic stem cell transplantation?

This study examined whether different types of coping and social support predict anxiety and depression in 212 hematopoietic stem cell transplant (HSCT) recipients. Data were collected prior to and 6 months after HSCT. Coping, social support, and gender predicted 26% of the variance in pre-HSCT anxiety and 24% of the variance in pre-HSCT depression. Coping and social support did not explain significant post-HSCT anxiety or depression when controlling for pretransplant anxiety or depression. High use of acceptance/ resignation coping, cognitive avoidance coping, lower tangible support, and lower belonging support were related to increased pre-HSCT anxiety and depression. Approach coping was not related to pre-HSCT anxiety. Patients who use acceptance/resignation coping and report low levels of two types of social support prior to HSCT may require additional intervention before HSCT, as they are at higher risk for depression and anxiety.

Neurocognitive impairment in children treated for cancer: how do we measure cognitive outcomes?

As the number of childhood cancer survivors grows, more attention on the identification and management of late effects, such as neurocognitive decline, is needed. This study, investigating treatment with central nervous system (CNS) stimulants for cognitive changes related to pediatric cancer treatment, confirmed a common concern. How should neurocognitive decline be measured and followed up after cancer therapy? Multiple pediatric standardized cognitive tests are available, but there is no consensus on an efficient way to measure the most common areas of decline, specifically impaired concentration, memory, and mental processing speed. The authors' report recognized 12 pediatric patients at risk for cognitive dysfunction, of whom 3 tested positive for early neurocognitive deficits using 3 subscales of the Wechsler Intelligence Scale for Children-III (WISC-III), which measure working verbal memory (Digit Span), mental processing speed (Symbol Search), and psychomotor speed (Coding). To predict the expected level of performance on WISC-III subscales, the patients' IQ was estimated using the Wide Range Achievement Test-3 reading subtest. Patients were treated with long-acting CNS stimulants and followed up serially using the WISC-III subscales.

Changes in cognitive functioning in the year after hematopoietic stem cell transplantation.

BACKGROUND: The current study examined changes in multiple domains of cognitive functioning of hematopoietic stem cell transplantation (HSCT) candidates tested pretransplantation, 6 months posttransplantation, and 12 months posttransplantation. METHODS: Using a sequential longitudinal design, 476 patients were randomized to be tested at all 3 time points, at 6 and 12 months posttransplantation, or at only 12 months posttransplantation. Participants completed a comprehensive battery of neuropsychologic tests that indexed memory, psychomotor speed, attention, and executive functioning, and provided a total neuropsychologic performance score (TNP). RESULTS: The results indicate that performance on cognitive abilities, except for attention, significantly improved across the 1-year follow-up period after HSCT. Performance on the TNP and all cognitive domains was superior or equal to population normative values by the 12-month measurement point. The results also indicate that repeated exposure to tests led to better performance on motor speed and the TNP and that attrition influenced the TNP, such that those who remained in the longitudinal sample exhibited greater longitudinal improvement in scores as compared with patients who left the sample. CONCLUSIONS: The findings of the current study suggest that although patients undergoing HSCT experience cognitive deficits during the period just before transplantation, cognitive functioning returns to normative values within a year after transplantation.

Alcoholism, depression, and abnormal cognition in head and neck cancer: a pilot study.

OBJECTIVE: To determine prevalence of alcohol abuse and dependency, depression, and cognitive impairment in presurgical head and neck cancer patients. STUDY DESIGN: Standardized testing by diagnostic interview was used to determine major depression and alcoholism. Mattis Dementia Rating Scale examined cognitive ability preoperatively. Twenty-four patients with advanced head and neck cancer participated. SETTING: University hospital. RESULTS: A total of 63.6% met criteria for alcohol abuse and 62 percent for alcohol dependence; 26.1 % of patients met criteria for major depression. Testing in multiple subsets of cognitive function demonstrated measurable deficits in both alcohol dependents and abusers. All deficits were significant when compared with population norms. CONCLUSIONS: Findings suggest that prevalence of alcohol abuse, major depression, and cognitive impairment is common in head and neck cancer patients preoperatively. Early diagnosis and management of these disorders should be considered in care of the head and neck cancer patient.

Evaluation of the functional assessment of cancer therapy cognitive scale with hematopoietic stem cell transplant patients.

The current study evaluated a newly developed self-report measure of cognitive complaints with cancer patients, the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog). Six or 12 months following hematopoietic stem cell transplantation, participants completed a psychosocial assessment that included the FACT-Cog and a neuropsychological assessment. Using a criterion of two or more times a week, an average of 12 of a total of 50 items were endorsed as complaints on the FACT-Cog. FACT-Cog total, domain, and subscale scores were significantly correlated with measures of depression, fatigue, anxiety, and physical and mental well-being. FACT-Cog scores, with the exception of one subscale, Other People Noticed Deficits, were not significantly correlated with cognitive performance. In general, the FACT-Cog and a commonly used measure of cognitive complaints (European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 Cognitive Functioning Scale) demonstrated similar psychometric properties. However, the FACT-Cog assesses broader aspects of cognitive complaints, thereby providing greater information about the types of cognitive complaints patients are experiencing.

Cognitive impairment in patients with brain tumors: assessment and intervention in the clinic setting.

Cognitive impairment is the most common neurologic problem associated with brain tumors and is present in many people with brain tumors from the time of diagnosis. Treatment of primary brain tumors with surgery, radiation, chemotherapy, and adjunctive medications such as corticosteroids results in further adverse effects on cognitive function. To plan the best care for patients with brain tumors, healthcare providers must initiate systematic and accurate assessment of cognitive functioning at the first clinic visit and extend assessment throughout the course of illness. This article outlines the range of cognitive dysfunction that may be seen in patients with primary brain tumors and offers information for clinicians seeking to develop their skills and implement a systematic approach to cognitive screening. The use of cognitive screening to guide timely intervention, such as referral to a neuropsychologist and the provision of anticipatory guidance to people with brain tumors and their families, is discussed.

Validation of the Distress Thermometer with bone marrow transplant patients.

The Distress Thermometer (DT) is a one-item screening measure of psychological distress in cancer patients. This study examines the operating characteristics of the DT in patients about to undergo bone marrow transplant (BMT). Patients (N=491) completed the DT, the Center for Epidemiological Studies-Depression Scale (CES-D), the State-Trait Anxiety Inventory-State Version (STAI-S), the ECOG Performance Status Scale, and the Patient Problem List. DT scores were related to higher depression, higher anxiety, and poorer performance status. Receiver operating characteristic (ROC) curve analyses of DT scores yielded area under the curve estimates of 0.75 when compared to the CES-D cutoff score of 16, suggesting the DT has acceptable overall accuracy. The DT cutoff score of 4 had the greatest sensitivity and specificity when compared to the CES-D cutoff score. Patients above this cutoff score reported worse ECOG scores and more practical, family, emotional, and physical problems (all p's< or =0.05) than those below the cutoff. The findings suggest the DT is a useful tool for screening for distress in BMT patients. The optimal DT cutoff score of 4 found here was identical to that found in another study using different criteria. This cutoff score also identified patients with problems likely to reflect psychological distress.