Daily living and rehabilitation needs in patients and caregivers affected by myeloproliferative neoplasms (MPN): A qualitative study.

AIMS AND OBJECTIVES: To explore experiences of daily living and identify rehabilitation needs in patients and caregivers living with myeloproliferative neoplasms. BACKGROUND: Myeloproliferative neoplasms are chronic haematological cancers. Studies report a high symptom burden but little is known about supportive care and rehabilitation for this patient group. DESIGN: Qualitative study with a phenomenological approach using focus group interviews to gather knowledge about the participants' lived experiences. METHODS: Forty-eight patients and seven caregivers attending a 5-day rehabilitation course were interviewed in 12 focus groups. Systematic Text Condensation was used to analyse the interviews. Reporting adhered to COREQ. RESULTS: Two main themes for patients were found: The loss of choice and identity due to the need to prioritise energy and The schism of being a person but also a patient. Patients described how living with myeloproliferative neoplasms meant having to prioritise energy and, therefore, losing freedom to choose activities. This changed their identity and impaired their quality of life. Patients of working age seemed to struggle the most in balancing the disease, family, social relationships and work. One main theme was found for caregivers: Influence of the disease. Caregivers reported how the disease limited their social lives, that the disease brought psychological strain, extra work, and that communication between couples was impaired. When both patients and caregivers participated in rehabilitation courses, they reported better understanding between couples and more open conversations. Rehabilitation needs identified were mainly in relation to psychosocial support and patient education, although needs varied across patients and caregivers. CONCLUSIONS: Patients and caregivers expressed difficulties in adjusting to the lives the disease enforced upon them. Our findings indicate that myeloproliferative neoplasms patients and their caregivers would benefit from a combined model of psychosocial support, patient education, peer support and rehabilitation interventions based on an individual needs assessment. RELEVANCE TO CLINICAL PRACTICE: Nurses can be responsible for individual needs assessments and refer patients and caregivers to suitable supportive care and rehabilitation interventions. TRIAL REGISTRATION DETAILS: The study was approved by the Danish Data Protection agency (J.nr. 2008-58-0035).

Tobacco use in the Myeloproliferative neoplasms: symptom burden, patient opinions, and care.

BACKGROUND: Patients with Philadelphia-negative Myeloproliferative Neoplasms (MPN) suffer from numerous symptoms and decreased quality of life. Smoking is associated with an increased symptom burden in several malignancies. The aim of this study was to analyze the association between smoking and MPN-related symptom burden and explore MPN patients' opinions on smoking. METHODS: A total of 435 patients with MPN participated in a cross-sectional internet-based survey developed by the Mayo Clinic and the Myeloproliferative Neoplasm Quality of Life Group. Patients reported their demographics, disease characteristics, tobacco use, and opinions on tobacco use. In addition, MPN-related symptoms were reported via the validated 10-item version of the Myeloproliferative Neoplasms Symptom Assessment Form. RESULTS: Current/former smokers reported worse fatigue (mean severity 5.6 vs. 5.0, p = 0.02) and inactivity (mean severity 4.0 vs. 3.4, p = 0.03) than never smokers. Moreover, current/former smokers more frequently experienced early satiety (68.5% vs. 58.3%, p = 0.03), inactivity (79.9% vs. 71.1%, p = 0.04), and concentration difficulties (82.1% vs. 73.1%, p = 0.04). Although not significant, a higher total symptom burden was observed for current/former smokers (mean 30.4 vs. 27.0, p = 0.07). Accordingly, overall quality of life was significantly better among never smokers than current/former smokers (mean 3.5 vs. 3.9, p = 0.03). Only 43.2% of the current/former smokers reported having discussed tobacco use with their physician, and 17.5% did not believe smoking increased the risk of thrombosis. CONCLUSION: The current study suggests that smoking may be associated with increased prevalence and severity of MPN symptoms and underscores the need to enhance patient education and address tobacco use in the care of MPN patients.

Health-Related Quality of Life in Patients with Philadelphia-Negative Myeloproliferative Neoplasms: A Nationwide Population-Based Survey in Denmark.

Previous studies have clarified that many patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have burdensome symptom profiles and accordingly impaired functioning and quality of life (QoL). In Denmark, all MPN patients are affiliated with public hospitals and because of a healthcare system financed by taxpayers these patients do not have any financial costs related to the hematological disease. Diagnoses are recorded for all patients in hospitals, and diagnosis codes are communicated to the National Patient Register (NPR). Owing to this, it was possible to contribute to the elucidation of Philadelphia-negative MPN patients' health-related quality of life (HRQoL), by conducting a nationwide, population-based, cross-sectional HRQoL survey of these patients with cost-free access to the best available, suitable medical treatment. The survey contained validated questionnaires covering functioning, symptom burden, symptom profile, QoL, and additional questions on lifestyle. Information on comorbid diagnoses was obtained from the NPR. The participants' HRQoL was compared to the general population. Moreover, differences in HRQoL across essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN participants were investigated, adjusted for age, sex, comorbidity, and lifestyle. To the best of our knowledge this is the first survey of HRQoL in patients with unclassifiable MPN. A total of 2228 Philadelphia-negative MPN patients participated. The participants reported their HRQoL to be inferior to the general population, but the difference was minor. The differences in HRQoL across groups of participants with different MPN subtypes were subtle. Fatigue and sexual problems were prevalent and burdensome. Overall, participants reported a slightly healthier lifestyle compared to the general population.

Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study.

We report the final 2-year end-of-study results from the first clinical trial investigating combination treatment with ruxolitinib and low-dose pegylated interferon-α2 (PEG-IFNα2). The study included 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEGIFNα2. The primary outcome was efficacy, based on hematologic parameters, quality of life measurements, and JAK2 V617F allele burden. We used the 2013 European LeukemiaNet and International Working Group- Myeloproliferative Neoplasms Research and Treatment response criteria, including response in symptoms, splenomegaly, peripheral blood counts, and bone marrow. Of 32 patients with polycythemia vera, ten (31%) achieved a remission which was a complete remission in three (9%) cases. Of 18 patients with myelofibrosis, eight (44%) achieved a remission; five (28%) were complete remissions. The cumulative incidence of peripheral blood count remission was 0.85 and 0.75 for patients with polycythemia vera and myelofibrosis, respectively. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score decreased from 22 [95% confidence interval (95% CI):, 16-29] at baseline to 15 (95% CI: 10-22) after 2 years. The median JAK2 V617F allele burden decreased from 47% (95% CI: 33-61%) to 12% (95% CI: 6-22%), and 41% of patients achieved a molecular response. The drop-out rate was 6% among patients with polycythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNα2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNα2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12.

Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association.

Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.

Anxiety and depression in patients with Philadelphia-negative myeloproliferative neoplasms: a nationwide population-based survey in Denmark.

OBJECTIVE: We sought to determine the prevalence and severity of anxiety and depression among patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) and respective associations of anxiety and depression with demographic and lifestyle factors, comorbidity burden, duration of MPN disease, financial difficulties, and health-related quality of life (QoL). METHODS: This study used data from a nationwide, population-based, cross-sectional survey of health-related QoL in MPN patients in Denmark called the MPNhealthSurvey. Individuals with a diagnosis of MPN in the National Patient Register were invited. The Hospital Anxiety and Depression Scale was used to assess the prevalence and severity of anxiety and depression. The associations of anxiety and depression with age, sex, education, body mass index (BMI), smoking, alcohol intake, physical activity, comorbidity burden, duration of MPN disease, financial difficulties, symptom burden, sexual problems, fatigue, functioning, and global health/QoL were examined. RESULTS: In total, 2,029 patients completed the Hospital Anxiety and Depression Scale. The prevalence of anxiety, depression, and both was 21%, 12%, and 8%, respectively. Many participants who reported anxiety or depression exhibited mild symptoms. Middle-aged and elderly participants had lower odds of experiencing anxiety and depression when compared to younger participants, and females had higher odds of anxiety compared to males. Participants with higher education had lower odds of anxiety compared to those with lower education. Current smokers and ex-smokers had higher odds of anxiety and depression compared to those who had never smoked, and sedentary participants and participants with a lower level of physical activity had higher odds of anxiety and depression compared to participants who performed hard training several times a week. Higher comorbidity burden increased the odds of depression, and greater financial difficulties increased the odds of anxiety and depression. Higher total symptom burden and fatigue burden and higher level of sexual problems increased the odds of anxiety and depression. Finally, lower functional level and global health/quality of life increased the odds of anxiety and depression. BMI, alcohol intake, comorbidity burden, and duration of disease were not substantially associated with anxiety, whereas sex, educational level, and duration of MPN disease were not substantially associated with depression. CONCLUSION: There may be an unmet need in handling psychological distress in MPN patients. Future research might explore the utility of screening for psychological distress and the effectiveness of lifestyle interventions, rehabilitation, and MPN-symptom reduction in preventing and treating psychological distress.

Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis.

Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon-α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low-/intermediate-1-risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon-α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow-up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty-seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon-α2 and ruxolitinib is efficacious in patients with low-/intermediate-1-risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.

The effectiveness of exercise-based rehabilitation to patients with myeloproliferative neoplasms-An explorative study.

The aim of the study was to determine the impact of an interdisciplinary exercise-based rehabilitation intervention on fatigue and quality of life (QOL) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs). At the Danish Knowledge Centre for Rehabilitation and Palliative Care, a 5-day interdisciplinary exercise-based rehabilitation intervention was carried out on 48 patients with MPN. It was followed by 12 weeks of self-exercising prior to follow-up. Initially and at follow-up, participants filled out validated questionnaires; Brief Fatigue Inventory, Multidimensional Fatigue Inventory, European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire, Myeloproliferative Neoplasm Symptom Assessment Form and Hospital Anxiety and Depression Scale. Maximal oxygen uptake and muscular strength were tested as well. Paired t test was used to compare scores between baseline and follow-up. In total, 45 participants (94%) completed the follow-up. No significant differences were observed on fatigue or QOL when comparing baseline and follow-up. Mean maximal oxygen uptake increased from 27.2 to 33.6 ml O2 · kg-1  ·min-1 (p < 0.001). Handgrip strength (p = 0.01) and the 30-s chair-stand test (p < 0.001) improved as well. No changes were found regarding levels of fatigue and QOL. However, we observed a significant increase in the physical capacity. Our observations call for further studies investigating the effects of non-pharmacological approaches in patients with MPN.

Associations between fatigue, physical activity, and QoL in patients with myeloproliferative neoplasms.

BACKGROUND: Patients with Philadelphia chromosome-negative Myeloproliferative Neoplasms (MPNs) report fatigue as the most common symptom and contributing significantly to reduction in their quality of life (QoL). Targeted non-pharmacological intervention to increase levels of physical activity is suggested as a fatigue-reducing and QoL-enhancing intervention in MPN patients. The interrelationship between physical activity, fatigue, and QoL has, to our knowledge, never been reported. METHODS: We analyzed data from 1807 MPN patients. The primary analysis included a multiple regression model allowing fatigue to mediate the relationship between physical activity and QoL. RESULTS: We herein report the first and the largest study of patients with MPNs, in whom we have investigated the interrelationship between fatigue, physical activity, and QoL. Sedentary patients were more likely to report fatigue compared to highly active patients. There was a negative association between fatigue and QoL, and there was a positive association between physical activity and QoL. There was no interaction between fatigue and physical activity in the association with QoL. CONCLUSION: We found positive associations between level of physical activity and QoL, independently of fatigue being present. More research is needed before physical activity can be introduced as a targeted intervention to reduce fatigue and increase QoL in the management of patients.

A nationwide population-based cross-sectional survey of health-related quality of life in patients with myeloproliferative neoplasms in Denmark (MPNhealthSurvey): survey design and characteristics of respondents and nonrespondents.

OBJECTIVE: The Department of Hematology, Zealand University Hospital, Denmark, and the National Institute of Public Health, University of Southern Denmark, created the first nationwide, population-based, and the most comprehensive cross-sectional health-related quality of life (HRQoL) survey of patients with myeloproliferative neoplasms (MPNs). In Denmark, all MPN patients are treated in public hospitals and treatments received are free of charge for these patients. Therefore, MPN patients receive the best available treatment to the extent of its suitability for them and if they wish to receive the treatment. The aims of this article are to describe the survey design and the characteristics of respondents and nonrespondents. MATERIAL AND METHODS: Individuals with MPN diagnoses registered in the Danish National Patient Register (NPR) were invited to participate. The registers of the Danish Civil Registration System and Statistics Denmark provided information regarding demographics. The survey contained 120 questions: validated patient-reported outcome (PRO) questionnaires and additional questions addressing lifestyle. RESULTS: A total of 4,704 individuals were registered with MPN diagnoses in the NPR of whom 4,236 were eligible for participation and 2,613 (62%) responded. Overall, the respondents covered the broad spectrum of MPN patients, but patients 70-79 years old, living with someone, of a Danish/Western ethnicity, and with a higher level of education exhibited the highest response rate. CONCLUSION: A nationwide, population-based, and comprehensive HRQoL survey of MPN patients in Denmark was undertaken (MPNhealthSurvey). We believe that the respondents broadly represent the MPN population in Denmark. However, the differences between respondents and nonrespondents have to be taken into consideration when examining PROs from the respondents. The results of the investigation of the respondents' HRQoL in this survey will follow in future articles.

A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis.

Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them. Most lately, it has been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful tool to differentiate between genuine ET and prePMF but needs to be validated in a larger cohort of "ET" patients.

A new internet-based tool for reporting and analysing patient-reported outcomes and the feasibility of repeated data collection from patients with myeloproliferative neoplasms.

PURPOSE: An Internet-based tool for reporting and analysing patient-reported outcomes (PROs) has been developed. The tool enables merging PROs with blood test results and allows for computation of treatment responses. Data may be visualized by graphical analysis and may be exported for downstream statistical processing. The aim of this study was to investigate, whether patients with myeloproliferative neoplasms (MPNs) were willing and able to use the tool and fill out questionnaires regularly. METHODS: Participants were recruited from the outpatient clinic at the Department of Haematology, Roskilde University Hospital, Denmark. Validated questionnaires that were used were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Myeloproliferative Neoplasm Symptom Assessment Form, Brief Fatigue Inventory and Short Form 36 Health Survey. Questionnaires were filled out ≥ 6 months online or on paper according to participant preference. Regularity of questionnaire submission was investigated, and participant acceptance was evaluated by focus-group interviews. RESULTS: Of 135 invited patients, 118 (87 %) accepted participation. One hundred and seven participants (91 %) preferred to use the Internet-based tool. Of the 118 enrolled participants, 104 (88 %) submitted PROs regularly ≥ 6 months. The focus-group interviews revealed that the Internet-based tool was well accepted. CONCLUSION: The Internet-based approach and regular collection of PROs are well accepted with a high participation rate, persistency and adherence in a population of MPN patients. The plasticity of the platform allows for adaptation to patients with other medical conditions.