Incurable but treatable: Understanding, uncertainty and impact in chronic blood cancers-A qualitative study from the UK's Haematological Malignancy Research Network.

OBJECTIVE: Most blood cancers are incurable and typically follow unpredictable remitting-relapsing pathways associated with varying need for treatment, which may be distressing for patients. Our objective was to conduct a qualitative study to explore understanding among patients with such malignancies, including the explanations given by HCPs and the impact of uncertain trajectories, to generate evidence that could guide improvements in clinical practice. METHODS: The study is set within a population-based patient cohort (the Haematological Malignancy Research Network), in which care is delivered across 14 hospitals according to national guidelines. In-depth interviews were conducted with 35 patients with chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphoma or myeloma; and 10 accompanying relatives. Purposive sampling ensured selection of information-rich participants and the data were interrogated using reflective thematic analysis. RESULTS: Rich data were collected and four themes (11 sub-themes) were identified: 1) Knowledge and understanding of chronic haematological malignancies; 2) Incurable but treatable; 3) Uncertainty about the future; and 4) Treatable (but still incurable): Impact on patients. Patients had rarely heard of blood cancer and many expressed difficulty understanding how an incurable malignancy that could not be removed, was treatable, often for long periods. While some were reassured that their cancer did not pose an immediate survival threat, others were particularly traumatised by the uncertain future it entailed, suffering ongoing emotional distress as a result, which could be more burdensome than any physical symptoms. Nonetheless, most interviewees understood that uncertain pathways were caused by the unpredictability of their disease trajectory, and not information being withheld. CONCLUSIONS: Many participants lacked knowledge about chronic haematological malignancies. HCPs acted to reassure patients about their diagnosis, and while this was appropriate and effective for some, it was less so for others, as the cancer-impact involved struggling to cope with ongoing uncertainty, distress and a shortened life-span.

Illness representations and psychological outcomes in chronic lymphocytic leukaemia.

OBJECTIVES: Chronic lymphocytic leukaemia (CLL) is a lifelong cancer with subtle symptoms. Treatment is not curative and often involves repeated relapses and retreatments. Illness perceptions - cognitive and emotional representations of illness stimuli - were studied in CLL patients to: 1) identify illness perception 'profiles' prior to treatment; and 2) test whether profile membership predicts psychological responses 12 months later as treatment continued. DESIGN: CLL patients (N = 259), randomized to one of four cancer treatment trials testing targeted therapy, were assessed before starting treatment and at 12 months. METHODS: The Brief Illness Perception Questionnaire (BIPQ) assessed perceived consequences, timeline, personal/treatment control, identity, comprehension, concern, and emotions toward CLL. Psychological outcomes were depressive symptoms (PHQ-9/BDI-II), negative mood (POMS), and cancer stress (IES-R). Latent profile analysis (LPA) determined number of profiles and differential BIPQ items for each profile. Multilevel models tested profiles as predictors of 12-month psychological outcomes. RESULTS: LPA selected the three-profile model, with profiles revealing Low (n = 150; 57.9%), Moderate (n = 21; 8.1%), and High-impact (n = 88; 34.0%) illness representations. Profiles were defined by differences in consequences, identity, concern, and emotions. Profile membership predicted all psychological outcomes (ps<.038). Low-impact profile patients endorsed minimal psychological symptoms; High-impact profile patients reported substantial symptoms. CONCLUSIONS: Results of the first CLL illness representation study provide directions for future clinical efforts. By identifying differences among patients' perceptions of CLL consequences, symptom burden, concerns, and emotional responses, an at-risk patient group might receive tailored psychological treatment. Treatments may address negative perceptions, to reduce psychological risk associated with chronic cancer.

Health-related quality of life and economic burden of chronic lymphocytic leukemia in the era of novel targeted agents.

OBJECTIVE: To quantify the health-related quality of life (HRQoL) and economic burden of chronic lymphocytic leukemia (CLL). METHODS: Studies were searched through Embase, MEDLINE, PubMed, and Cochrane Library, as well as conference abstracts (1 January 2000-2 June 2019). RESULTS: Overall, 12 and 17 primary studies were included in the HRQoL and economic burden reviews, respectively. Patients with CLL reported impairment in various quality of life domains when compared with healthy controls, including fatigue, anxiety, physical functioning, social functioning, depression, sleep disturbance, and pain interference. Key factors associated with a negative impact on the HRQoL burden of CLL included female gender, increased disease severity, and the initiation of multiple lines of therapy. Economic burden was assessed for patients with CLL based on disease status and the treatment regimen received. The main cost drivers related to CLL were outpatient and hospitalization-related costs, primarily incurred as a result of chemo/chemoimmunotherapy, adverse events (AEs), and disease progression. Treatment with targeted agents, i.e. ibrutinib and venetoclax, was associated with lower medical costs than chemoimmunotherapy, although ibrutinib was associated with some increased AE costs related to cardiac toxicities. Cost studies of targeted agents were limited by short follow-up times that did not capture the full scope of treatment costs. CONCLUSIONS: CLL imposes a significant HRQoL and economic burden. Our systematic review shows that an unmet need persists in CLL for treatments that delay progression while minimizing AEs. Studies suggest targeted therapies may reduce the economic burden of CLL, but longer follow-up data are needed.

Negative illness perceptions are related to more fatigue among haematological cancer survivors: a PROFILES study.

Objectives: The common sense model provides a theoretical framework for understanding substantial fatigue among (haematological) cancer survivors based on their illness perceptions. We therefore examined the associations between modifiable illness perceptions and substantial fatigue while controlling for sociodemographic, clinical, and psychological factors (symptoms of depression and anxiety) among haematological cancer survivors.Methods: Data from the population-based PROFILES registry were used. Survivors diagnosed between 1999 and 2013 with Hodgkin lymphoma (N = 164), non-Hodgkin lymphoma (N = 655) and chronic lymphocytic leukaemia (N = 174) were included. Survivors completed the Brief Illness Perception Questionnaire (B-IPQ), the Fatigue Assessment Scale (FAS), and Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regressions analyses were performed for the total group and three haematological cancers separately relating illness perceptions to substantial fatigue (>21 FAS).Results: Haematological cancer survivors with illness perceptions that represent more negative consequences (consequences, OR = 1.27; 95%CI = 1.13-1.42); attribute more symptoms to their illness (identity, OR = 1.29; 95%CI = 1.17-1.43); and have a poorer illness understanding (coherence, 1.13; 1.04-1.22) were more often substantially fatigued. For the remaining five illness perceptions, no significant association was found. Non-Hodgkin lymphoma survivors who reported a poor illness understanding (coherence, OR = 1.35; 95% CI = 1.06-1.72) and chronic lymphocytic leukaemia survivors who reported that treatment can control (OR = 1.25; 95%CI = 1.01-1.55) the illness experienced more often substantial fatigue.Conclusion: Those who experience more consequences of their disease, attribute more symptoms to their illness, and have a poorer illness understanding, have a higher risk to experience substantial levels of fatigue even years after diagnosis. Psychological interventions changing these illness perceptions may be beneficial in reducing fatigue among haematological cancer survivors.

Validation of the Chinese EORTC chronic lymphocytic leukaemia module - application of classical test theory and item response theory.

PURPOSE: The association of chronic lymphocytic leukemia (CLL) with health-related quality of life (HRQoL) is rarely studied globally. This study evaluated the psychometric properties of the EORTC-Chronic Lymphocytic Leukaemia (CLL17 [phase III]) module, a newly developed assessment on CLL patients' HRQoL, among Chinese CLL patients. METHODS: The Chinese CLL17, comprised of three subscales (symptom burden [SB], physical condition [PC] and worries/fears [WF]), was provided by the developer team through EORTC. A cross-sectional online survey was conducted to collect data. The classical traditional theory (CTT) and the item response theory (IRT) were used to evaluate the psychometric properties of CLL17. Internal consistency reliability was determined by the Cronbach's alpha and item-total correlation. Dimensionality was verified through confirmatory factor analysis (CFA). Convergent validity was also assessed. The generalized partial credit model was used for the IRT. The difficulty, discrimination, item fit, and differential item functioning (DIF) were calculated to assess the instrument's psychometric properties. RESULTS: In all, 318 patients, aged between 26 and 82 years, completed the questionnaire. A good level of internal reliability was achieved (Cronbach's alpha = 0.92). The item-total correlation coefficient ranged from 0.46 to 0.72. There was a mid-to-high correlation between CLL17 and domains of EQ-5D and QLQ-C30. The IRT model showed a satisfactory homogeneity, item fit and good discrimination of items, except for item 4, 6 and 16 (< 1.0). low information provided by item 16 and 17. SB and PC provided more information with theta > 0, whereas WF provided more information with theta < 0. Item 17 perform inconsistently for respondents from different age groups (DIF). CONCLUSION: The EORTC-CLL17 Chinese version shows acceptable reliability and validity, making it a valuable instrument to evaluate the impact on the HRQoL of Chinese CLL patients.

Identifying risk factors for depression and anxiety symptoms in patients with chronic lymphocytic leukemia.

PURPOSE: This study assessed whether empirically supported risk factors can identify future depression and anxiety symptoms in a specific cancer type, chronic lymphocytic leukemia (CLL). METHODS: Patients enrolled in a CLL treatment clinical trial (N = 106) participated at baseline following informed consent and prior to treatment initiation. Risk factors with empirical support (personal or family psychiatric history, recurrent, advanced or progressive disease, low socioeconomic status, gender, medical comorbidities, and single marital status) and additional risk factors (cancer-specific stress, social contacts, negative life events, absolute lymphocyte counts, treatment group, and fatigue) were measured at baseline to predict depression and anxiety symptoms at 12 months. RESULTS: Data show 14% (n = 15) and 12% (n = 13) of patients experienced moderate-severe depression and anxiety symptoms, respectively. Multiple linear regression analyses found medical comorbidities predicted 12-month anxiety symptoms (p < 0.05). Also, negative life events predicted depression and anxiety symptoms and fatigue predicted depression symptoms (p < 0.05). CONCLUSION: Empirically supported risk factors associated with depression and anxiety symptoms are limited in predicting future depression and anxiety symptoms beyond initial screening in patients with CLL. In addition to levels of depression and anxiety symptoms at baseline, negative life events, higher levels of fatigue, and greater medical comorbidities were associated with future depression or anxiety symptoms in patients with CLL.

Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor T Cell Therapy.

CD19-targeted chimeric antigen receptor (CAR) modified T cell immunotherapy is a novel treatment with promising results in patients with relapsed/refractory lymphoid malignancies. CAR T cell therapy has known early toxicities of cytokine release syndrome and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects. We have used patient-reported outcomes, including Patient-Reported Outcomes Measurement Information System (PROMIS) measures, to assess neuropsychiatric and other patient-reported outcomes of 40 patients with relapse/refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and acute lymphoblastic leukemia 1 to 5 years after treatment with CD19-targeted CAR T cells. Mean T scores of PROMIS domains of global mental health, global physical health, social function, anxiety, depression, fatigue, pain, and sleep disturbance were not clinically meaningfully different from the mean in the general US population. However, 19 patients (47.5%) reported at least 1 cognitive difficulty and/or clinically meaningful depression and/or anxiety, and 7 patients (17.5%) scored ≤40 in global mental health, indicating at least 1 standard deviation worse than the general population mean. Younger age was associated with worse long-term global mental health (P = .02), anxiety (P = .001), and depression (P= .01). Anxiety before CAR T cell therapy was associated with increased likelihood of anxiety after CAR T cell therapy (P = .001). Fifteen patients (37.5%) reported cognitive difficulties after CAR T cell therapy. Depression before CAR T cell therapy was statistically significantly associated with higher likelihood of self-reported post-CAR T cognitive difficulties (P = .02), and there was a trend for an association between acute neurotoxicity and self-reported post-CAR T cognitive difficulties (P = .08). Having more post-CAR T cognitive difficulties was associated with worse global mental health and global physical health. Our study demonstrates overall good neuropsychiatric outcomes in 40 long-term survivors after CAR T cell therapy. However, nearly 50% of patients in the cohort reported at least 1 clinically meaningful negative neuropsychiatric outcome (anxiety, depression, or cognitive difficulty), indicating that a significant number of patients would likely benefit from mental health services following CAR T cell therapy. Younger age, pre-CAR T anxiety or depression, and acute neurotoxicity may be risk factors for long-term neuropsychiatric problems in this patient population. Larger studies are needed to confirm these findings.

Illness Perceptions in Chronic Lymphocytic Leukemia: Testing Leventhal's Self-regulatory Model.

BACKGROUND: Leventhal's Self-regulatory Model proposes that somatic characteristics of a health threat (e.g., symptom severity), and prior experience with the threat (e.g., unsuccessful treatment), are determinants of illness perceptions. Chronic lymphocytic leukemia (CLL) is appropriate for test of these postulates, having three phases differing in symptom severity and prior treatment experiences: indolent disease requiring no treatment (active surveillance; AS), symptomatic disease requiring a first treatment (FT), and highly symptomatic disease in those who have relapsed and/or failed to respond to prior treatments (relapsed/refractory; RR). PURPOSE: To test symptom severity and prior treatment experiences as determinants of illness perceptions, illness perceptions were characterized and contrasted between CLL groups. METHODS: Three hundred and thirty CLL patients (AS, n = 100; FT, n = 78; RR, n = 152) provided illness perception data on one occasion during a surveillance visit (AS) or prior to beginning treatment (FT, RR). RESULTS: Analysis of variance with planned comparisons revealed that consequences, identity, and concern were least favorable among RR patients, followed by FT, then AS (ps < .01). AS patients endorsed the lowest levels of coherence (ps < .01), and the most chronic illness timeline (ps < .01). FT patients endorsed the highest levels of personal and treatment control (ps < .01). CONCLUSIONS: Data provide preliminary empirical support for Self-regulatory Model postulates that symptom severity and prior disease experiences influence illness perceptions. Unique knowledge needs for AS patients and elevated psychological/physical symptoms for later-stage CLL patients may warrant clinical attention.

Juniper Subtle Energy Healing: A Case Study.

OBJECTIVES: This pilot case study sought to examine the efficacy of subtle energy treatments as conducted by Buddhist healing master Segyu Rinpoche at his Juniper Integrative Clinic in Northern California. DESIGN: Over the course of a year, this study followed two patients with terminal diagnoses, their treating physicians, and Segyu Rinpoche as the patients underwent treatment at the Juniper Clinic. The patients entering the study had exhausted all known medical options. One patient suffered from chronic lymphocytic leukemia [CLL] and the other from bronchiolitis obliterans [BOS] brought about by graft versus host disease following a bone marrow transplant for leukemia. Their treating physicians are prominent members of two different teaching/research hospitals. This was an IRB approved study conducted in conformity with HIPAA standards. SETTING: The patients participated in treatments with Segyu Rinpoche twice a month at his clinic and engaged in daily meditation as instructed by Rinpoche. The study followed both patients through in-depth, face-to-face interviews, wellness surveys, weekly journal entries, and medical records. The study also followed the physicians and Segyu Rinpoche through face-to-face interviews. RESULTS: Both patients and physicians identified significant shifts in patient wellbeing, including less pain, greater happiness and more ease. In addition, both physicians and patients reported a reduced need for medication. Some aspects of the design were more or less successful in tracking patient experience (i.e., health and wellness survey vs. personal journals). The success of the pilot indicates that more qualitative case studies are needed. CONCLUSIONS: Patients and physicians identified a significant increase in overall patient wellbeing. Hence, on an anecdotal level, the study demonstrated the usefulness of subtle energy healing as practiced by Segyu Rinpoche and the Juniper Clinic. The success of the pilot indicates the potential value of full qualitative studies for this modality.

Cancer-Specific Stress and Trajectories of Psychological and Physical Functioning in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia.

Background: Chronic lymphocytic leukemia is the most prevalent adult leukemia. The disease is incurable with a cycling of treatment and relapse common. Little is known about the psychological and physical functioning of patients with relapsed/refractory chronic lymphocytic leukemia. Cancer-specific stress is an important individual difference variable that predicts psychological and physical outcomes. Purpose: To examine cancer-specific stress at treatment initiation as a predictor of psychological and physical functioning trajectories in patients with relapsed/refractory chronic lymphocytic leukemia during the first 5 months of treatment. Methods: Patients with relapsed/refractory chronic lymphocytic leukemia (N = 152) enrolled in a phase II clinical trial completed self-report measures at treatment initiation (baseline), 1, 2, and 5 months of treatment. Cancer-specific stress at baseline was examined as a predictor of psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems, physical health quality of life), controlling for demographic and treatment variables. Results: Using multilevel modeling, higher baseline cancer-specific stress was related to worse psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems) at baseline and more rapid improvements during the next 5 months. Despite these improvements, higher baseline cancer-specific stress remained associated with poorer 5-month psychological, though not physical, functioning. Conclusions: Findings suggest cancer-specific stress at treatment initiation may be a risk factor for poorer psychological functioning during treatment for patients with relapsed/refractory chronic lymphocytic leukemia.

Cells, cytokines, chemokines, and cancer stress: A biobehavioral study of patients with chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied. Before the first dose, a validated self-report measure of stress (the Impact of Event Scale) was completed, and blood was drawn for absolute lymphocyte counts (ALCs) and for cytokine and chemokine enzyme-linked immunosorbent assays. Multiple linear regression models tested stress as a concurrent predictor of ALCs; of cytokines (tumor necrosis factor α [TNFα], a proliferation-inducing ligand [APRIL], B-cell activating factor [BAFF], interleukin 6 [IL-6], IL-10, IL-16, and vascular endothelial growth factor [VEGF]); and of the chemokine (C-C motif) ligand 3 (CCL3). RESULTS: Controlling for relevant demographic variables, comorbidities, CLL genetic risk (deletion of the short arm of chromosome 17 [del17p]), and correlates of inflammation, stress predicted higher ALCs (P < .05), and higher levels of TNFα (P < .05), IL-16 (P < .01), and CCL3 (P < .05). Stress was not associated with APRIL, BAFF, IL-6, IL-10, or VEGF. CONCLUSIONS: Novel biobehavioral data from patients with relapsed/refractory CLL demonstrate that stress is related to heightened levels of cellular, cytokine, and chemokine markers associated previously with progressive disease in CLL. The current results indicate that stress is related to immune and inflammatory processes that contribute to cancer cell proliferation and survival. These data provide a first look into these processes. Cancer 2018. © 2018 American Cancer Society.

More frequent use of health care services among distressed compared with nondistressed survivors of lymphoma and chronic lymphocytic leukemia: Results from the population-based PROFILES registry.

BACKGROUND: Follow-up care for a growing population of survivors of lymphoma and chronic lymphocytic leukemia (CLL) together with the adverse effects these survivors may experience as a result of their cancer and treatment have led to more pressure being placed on health care services. The objectives of the current study were to: 1) compare the use of medical care services by survivors with that of a normative population; 2) evaluate the use of medical and psychosocial care services among distressed and nondistressed survivors; and 3) identify associated sociodemographic and clinical factors. METHODS: Survivors of lymphoma and CLL diagnosed between 1999 and 2012 were selected via the population-based Netherlands Cancer Registry and completed the Hospital Anxiety and Depression Scale questionnaire and questions regarding health care. Outcomes were compared with an age-matched and sex-matched normative population. RESULTS: A total of 1444 survivors responded (69%). Survivors of lymphoma and CLL contacted their general practitioner (3.8 vs 2.3; P<.001) and medical specialist (5.7 vs 1.6; P<.001) more often within the last year compared with a normative population. In addition, psychologically distressed survivors had even more medical contacts and received psychosocial care more often compared with nondistressed survivors. In addition to psychological distress, comorbidity, female sex, and older age were found to be associated with a greater use of medical services, whereas younger age was associated with receiving psychosocial care. CONCLUSIONS: Survivors of lymphoma and CLL, especially those who are psychologically distressed, report an increased use of health care services compared with a normative population. Further studies are needed to explore whether the use of widely applicable psychosocial interventions could reduce the frequency of medical contacts. Cancer 2018;124:3016-24. © 2018 Netherlands Comprehensive Cancer Organisation. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

In Remission: A Patient's Experience of Continued Care After Chronic Lymphocytic Leukemia

Being a patient with chronic lymphocytic leukemia and now in the midst of infusion treatment after a 17-year remission, I cannot praise oncology nurses enough. I am overwhelmed by their professionalism and warmth and I am delighted to share my perspective as a patient.

Improving shared decision-making in chronic lymphocytic leukemia through multidisciplinary education.

New treatments for chronic lymphocytic leukemia (CLL) with excellent response rates and varying toxicity profiles have emerged in recent years, creating an opportunity for a patient's personal preferences to contribute to treatment decisions. We conducted a prospective, quasi-experimental pre- and post-evaluation of a multilevel educational program and its impact on knowledge of CLL and shared decision-making (SDM). We educated patients, lay navigators, nurses/advanced practice providers (APPs), and physicians. Patients were evaluated for change in patient activation, distress, desired role in decision-making, perception of decision-making, satisfaction with oncologist explanation of treatment choice, and knowledge of CLL. Lay navigators, nurses/APPs, and physicians were evaluated for change in CLL knowledge and perception of decision-making. Forty-four patients, 33 lay navigators, 27 nurses/APPs, and 27 physicians participated in the educational program. We observed trends toward improved patient activation, with 68% before education versus 76% after education reporting a Patient Activation Measure (PAM) score of 3 or 4. The percentage of patients desiring and perceiving SDM trended upward from 47% to 67% and from 35% to 49%, respectively. The percentage of patients understanding that CLL is incurable increased from 80% to 90%, as did reporting awareness of signs of progression (64% to 76%). Patients' satisfaction with their oncologists' explanations of therapy increased significantly from 83% to 95% (p = .03). CLL knowledge increased after education for lay navigators (36% vs 63%) and nurses/APPs (35% vs 69%), and remained high for physicians (85% vs 87%). Nurses/APPs and physicians perceived at least some patient involvement in decision-making at baseline, whereas 12% of patients and 23% of lay navigators perceived that physicians made decisions independently. This project demonstrated trends toward improvements in patient engagement, prognostic awareness, knowledge of signs of progression, and SDM. These promising findings should be tested in larger samples. There remains an opportunity for further improvement in SDM.

[Efficacy of a bendamustine and rituximab combination in first-line therapy for chronic lymphocytic leukemia: Results of the BEN-001 study]. / Éffektivnost' kombinatsii bendamustina i rituksimaba v pervoi linii terapii KhLL: rezul'taty issledovaniia BEN-001.

AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping. A centralized approach was employed to make IGHV gene mutational status analysis, FISH examination, and minimal residual disease according to standardized methods. Quality-of-life (QOL) indicators were estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were calculated applying by the Kaplan-Meier method. RESULTS: The patients' median age was 61 years. 41% of patients had a decline in estimated creatinine clearance less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could achieve a common response in 83.2% of the patients, including complete remission in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of 84 patients. Two-year progression-free survival rates were 85.9%. The QOL indicators were noted to be improved during the treatment. CONCLUSION: The investigation shows the good tolerability of bendamustine when it is used in clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab, ofatumumab, etc.) and toxicity of the FCR regimen, the combination including bendamustine can be the best first-line therapy option for all CLL patients, regardless of their age and comorbidity.

Individual differences in physical symptom burden and psychological responses in individuals with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an incurable illness, with some patients requiring no treatment until disease progression. Burden from physical symptoms has been associated with depression, anxiety, and stress in cancer patients. Additionally, patient factors, i.e., individual differences, have been associated with worse psychological outcomes. There are few psychological studies of CLL, with no examination of individual differences. A cross-sectional design studied the covariation of symptom burden with depressive and anxiety symptoms and cancer-specific stress, and tested patients' individual differences as predictors and as moderators. CLL patients (N = 112) receiving active surveillance participated. They were Caucasian (100 %) and predominately male (55 %) with a mean age of 61; most (62.5 %) had stage 0 disease. A composite measure of physical symptom burden (CLL symptoms, fatigue, pain, impaired functional status) was tested as a predictor of psychological responses. Individual differences in psychiatric history and social support were tested as moderators. Using multiple linear regression, greater symptom burden covaried with higher levels of depressive and anxiety symptoms and cancer stress (ps < .05). Those with a psychiatric history, low social support, and low relationship satisfaction with one's partner reported greater symptom burden and more psychological symptoms and stress (ps < .05). Findings suggest that CLL patients in surveillance with a psychiatric history and/or low social support are at risk for greater distress when coping with high symptom burden. These new data clarify the experience of CLL surveillance and identify characteristics of patients with heightened risk for symptom burden, stress, and anxiety or depressive symptoms.

The relation of illness perceptions to stress, depression, and fatigue in patients with chronic lymphocytic leukaemia.

OBJECTIVE: Chronic lymphocytic leukaemia (CLL) is the most prevalent adult leukaemia and is incurable. The course and treatment of CLL is unique and characterised by repeated cycles of treatment, stable disease and relapse. Utilising a Self-Regulatory Model framework, we examined the relationship between patients' illness perceptions and cancer-specific stress, depressive symptoms and fatigue. Our aim was to test illness perceptions as predictors of these outcomes when variance due to disease and treatment variables was controlled. DESIGN: Data were collected on 147 patients with relapsed/refractory CLL as they entered a phase II clinical trial of an investigational medication at a university affiliated, National Cancer Institute designated comprehensive cancer center. MAIN OUTCOME MEASURES: Cancer-specific stress, depressive symptoms and fatigue interference. RESULT: . Hierarchical multiple regression was used. Consequences and emotional representation were related to all outcomes (ps < .01). Illness concern was related to cancer-specific stress (p < .01), and identity was related to fatigue interference (p < .01). All relationships were observed while controlling for number of previous CLL therapies received. CONCLUSION: Illness perceptions are related to cancer-specific stress, depressive symptoms and fatigue interference in relapsed/refractory CLL. Interventions targeted at restructuring maladaptive illness perceptions may have clinical benefit in this population.

Economic Burden and Quality-of-Life Effects of Chronic Lymphocytic Leukemia: A Systematic Review of the Literature.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia in the Western hemisphere. The disease affects quality of life (QOL) and poses an economic burden on patients, payers, and society. The objective of this review was to quantify the economic burden and quality-of-life effects and identify the gaps that should be addressed by future research. METHODS: Free-text and subject heading searches in MEDLINE, EMBASE, the Cochrane Library, the University of York Centre for Reviews and Dissemination Database, and the Web of Science Core Collection database were conducted to identify observational and interventional studies reporting costs and/or quality-of-life effects published up to 2 October 2015. Studies were included irrespective of whether they were conducted prospectively or retrospectively. The focus population consisted of adult patients aged 18 years or older affected by any stage of CLL. Studies were included regardless of whether the underlying population was treated at baseline or not. Risk of bias was assessed using a quality checklist developed by the Effective Public Health Practice Project for (randomized) controlled trials, cohort studies, and cross-sectional studies. Economic evaluations were rated using a checklist developed by Stuhldreher et al. (Int J Eat Disord 45:476-91, 2012). RESULTS: From 2451 records identified, 27 studies were found to be eligible for inclusion. Studies were heterogeneous with respect to methodology, perspective, and data used. Annual direct costs per person ranged from US$4491 in Germany to US$43,913 in the USA. The share of costs attributable to drug treatment varied between 26.2 and 79 %. Indirect costs amounted to US$4208. Severity of disease was a predictor for quality of life, whereas differences by age and sex were mainly present in subdomains. Comparisons of treated and untreated populations resulted in an increase of quality of life in favor of treated populations in the long-term perspective. Differences between treatments were small. Consequently, cost effectiveness in decision-analytic models did not depend on whether quality of life or survival are used to describe the benefits of treatment. CONCLUSIONS: Although the quantity and the quality of health economic and quality-of-life evidence have substantially increased, there is still a need for studies that take a patient or societal perspective. Factors that influence costs and the quality of life of patients seem to be well-established, while longitudinal lifetime cost studies at the population level are still scarce.