McCallister, Archie

Abstract Background Symptom burden among MPN patients is severe compared to age-matched controlled and other individuals with cancer. MPN-Related Fatigue (MRF) is among one of the most frequent and debilitating of symptoms among MPN patients and contributes greatly to the loss of quality of life. To date, little is known regarding the breadth and efficacy of strategies to reduce or palliate MRF. Methods A 17-item internet-based survey was hosted on the MPN Forum website during February of 2013. The survey included data on demographics, type of fatigue (chronic, sporadic, or both), strategies to reduce fatigue, and symptom burden using the MPN-SAF TSS. The MPN-SAF TSS also included a validated 1-item measure to assess worst fatigue in the last 24 hours (scored on a 0 (absent/as good as it can be) to 10 (worst-imaginable/as bad as it can be) scale). Results 879 MPN patients responded to the online survey. The majority of patients had been diagnosed with their MPN for more than one year (5.8% less than one year, 34.4% one to five years, 30.3% five to ten years, and 27.6% more than 10 years). Mean age of MPN diagnosis was 49.3 (range 12-84). A near equal mix was seen of chronic (35.3%), sporadic (29.9%) and both chronic and sporadic fatigue (28.8%). Average symptom burden was very severe (mean MPN-SAF TSS =31.9), with an average worst 24-hr fatigue rated as 5.9/10. Many strategies to reduce MPN-related fatigue were mentioned via open and categorical responses (Table 1). Exercise was the most commonly mentioned fatigue reduction strategy, followed by diet and social interaction. Diet strategies included the consumption of fruits and vegetables and using foods to combat specific nutrient deficiencies (e.g., iron). Interventions to increase rest included obtaining >8 hours of sleep at night, taking frequent naps if needed, and strategically timing naps (e.g., sleeping prior to activity). Timing strategies were implemented to maximize energy levels, including scheduling activities at time periods during the day when patients felt most awake. Stress-reduction strategies included massages, meditation and yoga. Some respondents felt work was both source of energy and motivation, although others mentioned cutting back work hours or obligations in order to reduce fatigue. New activities such as gardening and enjoying the outdoors were also mentioned. Use of non-prescription supplementation, including caffeine and over-the counter energy supplementation, was common. Prescription energy stimulants included MPN-specific treatments (e.g., ruxolitinib, hydroxurea, ASA, interferon), steroids, noradrenergic stimulants (e.g., methyphenidate, modafinil), prescription vitamin supplements (e.g., vitamin B12 injections), erythropoietin analogues, and blood thinners. Conclusions Overall patients were very symptomatic of disease (previously reported MPN-SAF TSS scores 18.7 ET, 21.8 PV, and 25.3 MF) and worst 24-hr fatigue (previously reported as 4.0 ET, 4.4 PV, and 5.0 MF) than previously published MPN cohorts (JCO 2012 20;30(36):4590). Many intervention strategies are utilized to reduce MRF. Future trials investigating pharmacologic, psychosocial, and activity-related interventions to reduce MRF are needed. Disclosures: Harrison: NOVARTIS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; Sbio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Abstract Background: The Philadelphia chromosome negative chronic myeloproliferativeneoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera(PV), and myelofibrosis (MF) are a group of diseases of myeloid clonal lineage with significant symptom burden. MPN patients have also been found to have a high likelihood of mood disturbance related to their MPN, including symptoms of depression and anxiety (BMC Cancer. 201616:167). To date, the relationship between disease factors and depressive symptoms among MPN patients has not been well characterized. Methods: We have previously published the results of a 70-item internet-based survey which evaluated fatigue-relieving strategies among MPN patients (Cancer. 2016 Feb 1;122(3):477-85). Surveyed data included mental health questionnaires including a measure of symptoms of depression, the PHQ-2, (Ann Fam Med. 2010. 8(4): 348-353), a measure of positive and negative moods the POMS-short form (J Nerv Ment Dis. 1979;167(10):612-4) and a measure of symptoms of depression and anxiety, the MHI-5 (J Consult Clin Psychol. 1983. 51;730-742). This abstract is a secondary analysis of data collected among this cohort. Data: Demographics A total of 1788 individuals diagnosed with an MPN participated in the survey. 1389 patients answered questions regarding mood and psychological comorbidities. Many MPN patients reportedthat they had been seen by a health provider for care or diagnosis of depression (32%), anxiety (29.5%), stress (26.2%), or grief(15.0%). Overall, 24.0% of ET, 22.2% of PV, and 22.9% of MF patients endorsed symptoms of depression based on their score of greater than or equal to 3 on the PHQ-2. Demographic and Psychosocial Correlates Younger patients were significantly more likely to have PHQ-2 score of equal to or greater than three (57.0 years vs 59.5 years, p=0.0006). Gender, race, and country of origin did not significantly correlate with screening positive for symptoms of depression. Higher BMI was associated with a higher likelihood of screening positive for symptoms of depression (BMI 26.2 vs 24.6, p=0.005). Not surprisingly, having received treatment for mood problems in the last 6 months (p<0.0001) along with medications for mood disorders (p=0.03) were significantly associated with increased symptoms of depression. Specifically, the use of psychostimulants (p<0.0001), antidepressants (p<0.0001), anti-anxiety medications (p=0.0005) and prescription pain medications (p<0.001), were significantly associated with elevated PHQ-2 score. Individuals with lower educational attainment were more likely to endorse depressive symptoms (p=0.0001) as well as those who were unable to work from home due to a medical disability (p<0.0001). Tobacco use was significantly associated with depressive symptoms (p=0.0002). Symptom and Mental Health Correlates Increased MPN-SAF TSS (MPN-10) score and all individual symptom items in the MPN-SAF were significantly associated with symptoms of depression (p<0.0001, Table 1). Increased POMS-B Subscales scores and total score along with lower MHI score was associated with positive depression screening. When asking patients what interventions they had tried to reduce fatigue, those who endorsed volunteer activities (18% vs 25.4%, p= 0.0062) and exercise (19.7% vs 32.2, p<0.0001) were significantly less likely to screen positive for symptoms of depression. Prognostic Risk Scoring Correlates For MF, PV and ET prognostic risk scoring did not significantly correlate with PHQ score (for all, P>0.005). Conclusions Depression and mood disorders among individuals with malignancy represent a particular challenge for health care providers, particularly in MPN patients who have been found to have a higher risk of depression than the general population. In our cohort, prognostic risk did not correlate with risk of depression. Based on these findings, it is critical that physicians who see MPN patients should closely monitor these patients for signs of depression and provide appropriate treatment when needed. Continued investigation into treatment of mood disorders among MPN patients is warranted, as patients may benefit from both symptom-directed therapies as well as traditional therapies. Encouragement of volunteering and exercise activities should be considered for thesepatientsas participation may be associated with improved mood status. Disclosures Harrison: Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau. Mesa:Galena: Consultancy; Incyte: Research Funding; Gilead: Research Funding; Novartis: Consultancy; CTI: Research Funding; Promedior: Research Funding; Ariad: Consultancy; Celgene: Research Funding.

Abstract Background Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) represent three of the most common Philadelphia chromosome negative myeloproliferative neoplasms (MPN). Individuals with these disorders suffer from excessive debilitating fatigue compared to age-matched controls. Although cytokine deregulation and impaired hematopoiesis contributes to the intrinsic causes of MPN-related fatigue, there may be contributory effects of underlying mood. To date few studies have prospectively evaluated the role of mood disorders on fatigue among this population. Methods A 70-item internet-based survey was developed by MPN investigators and patient/advocates and hosted by the Mayo Clinic Survey Research Center. The survey was promoted online via multiple MPN-related webpages including the MPN Forum, MPN Net, MPN Research Foundation, and MPN Voice during February/March of 2014. Surveyed data included disease demographics such as splenomegaly, thrombosis, hemorrhage transfusions, medications, and phlebotomies. The MPN-SAF (including the MPN 10), and Brief Fatigue Inventory were used to assess disease burden (Blood. 2011 14;118(2):401-8). Mental health was assessed using the Profile of Mood States (POMS-short form (J Nerv Ment Dis. 1979;167(10):612-4)), Patient Health Questionaire (PHQ-2 (Ann Fam Med. 2010. 8(4): 348–353)) and Mental Health Inventory (MHI-5 (J Consult Clin Psychol. 1983. 51;730-742)). Results Demographics: Overall 1788 MPN patients participated in the survey. Of these, 1676 consented to participate and provided additional data (answered at least 10 questions). Of these, 555 (33%) patients had ET, 651 (39.0%) have PV, and 417 (25.0%) have MF. Respondents were 68% female with a mean age of 59. Overall brief fatigue inventory score had a mean of 4.4 (range 0-10). MPN-10 score average was 28.4 (range 0-83). Psychological Comorbidities: Mental health assessments were obtained among participants. Mean PHQ-2 score was 1.6 (SD = 1.6, range 0-6.0). Twenty three percent of respondents scored greater than or equal to three on the PHQ-2 indicating a high probability of depression (mean = 1.6 (SD = 1.6, range 0-6)). Additionally, average MHI-5 score was 21.8 (SD = 4.9), with scores less than 60 likely representing a mental disorder with minimal misclassification rate (BMC Psychiatry. 2008. 19;8:10). Mean POMS-B score was 76.9 (SD=19.9, mean subscale scores: tension-anxiety 15.1, vigor-activity 6.0, fatigue-inertia 10.0, depression-dejection 15.5, confusion-bewilderment 14.3, anger-hostility 15.7). Patients frequently endorsed having being seen for or diagnosed with depression (32.0%), anxiety (29.5%), stress (26.2%), and grief (15.0%). Of participants, 22.2% had received active treatment of a mood disorder in the past 6 months. When queried on treatments of mood disorders, respondents often had received medication treatments (81.4%), counseling/therapy (40.3%), and group therapy (6.0%). Correlations: Many significant correlations were observed between MPN-SAF items and PHQ, MHI-5, and POMS-B (Table 1). When evaluating likelihood of depressive symptoms (as assessed by a PHQ), survey items including older age (p= 0.0006) and lower educational attainment (p=0.0001) were noted to have significant association with depressive symptoms . Higher BFI, MPN-10, and individual MPN-SAF scores were significantly associated with a higher likelihood of depressive symptoms (p<0.0001). Conclusions Overall many MPN patients reported having had coexisting mood disorders. The frequency of mood disturbance is likely greater than that in the general population (e.g., 11% of individuals in the primary care population have PHQ-2 greater than or equal to 3 (Ann Fam Med. 2010; 8(4): 348–353) and average control population POMS-B total mood disturbance score = 34.1 (BioPsychoSocial Medicine 2011, 5:6)). The causality of relationship between mood disorders and MPN-related fatigue severity is not entirely clear, fatigue could contribute to depressive symptoms, depression could cause fatigue, or it can be bidirectional. Thus mood disorders may represent a primary or secondary process in the disease course. Evaluation of MPN-related fatigue should be multifactorial, and should take into consideration underlying mood disorders as part of a comprehensive assessment and subsequent treatment regimen. Disclosures Harrison: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Gilead: Honoraria; SBio: Consultancy; Shire: Speakers Bureau. Mesa:Incyte: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; Ns Pharma: Research Funding; Celgene: Research Funding; Lilly: Research Funding; Cti: Research Funding.

Abstract Background: Philadelphia chromosome negative myeloproliferative neoplasms (MPN) include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). Pertinent to these disorders is the high persistence, prevalence, and severity of fatigue. Overall, excessive fatigue compared to age and gender matched controls occurs in greater than 95% of MPN patients (Blood. 2011;118(2):401-8). Physiologic etiologies of fatigue in these patients include cytokine dysregulation and impaired hematopoiesis, however to date no one has investigated the impact that cofounding medical illnesses have on MPN fatigue burden. Methods: A 70-item internet-based survey was developed by a team of MPN investigators, patient advocates from MPN Forum, and hosted by the Mayo Clinic Survey Research Center. The survey was promoted online via multiple MPN-related webpages including the MPN Forum, MPN Net, MPN Research Foundation, and MPN Voice during late February to March of 2014. Surveyed data included disease demographics such as splenomegaly, thrombosis, hemorrhage transfusions, medications, and phlebotomies. The MPN-SAF (including the MPN 10) was utilized including the 10-item brief fatigue inventory was used to assess disease burden (Blood. 2011 Jul 14;118(2):401-8). Comorbid conditions were assessed, including hypothyroidism, anemias, sleep disturbances, obesity, and heart and lung disorders. Data: Demographics. Overall 1788 MPN patients participated in the survey. Of these, 1676 consented to participate and provided additional data (i.e., completed at least 10 questions). Of these, 555 (33%) patients had ET, 651 (39.0%) had PV, and 417 (25.0%) had MF. Among MF patients, 44.1% had primary MF, 29.7% had post-PV MF, and 26.2% had post-ET MF. Respondents were 68% female with a mean age of 59. Overall brief fatigue inventory score had a mean of 4.4 (range 0-10). MPN-10 score average was 28.4 (range 0-83). Medical Comorbidities. Overall, many patients endorsed having comorbid medical diseases that could contribute to overall fatigue (Table1). Overall 20.2% of patients endorsed having low thyroid function, with 10% indicating they obtained this diagnosis in the last six months. Twenty three percent endorsed having a new sleep disturbance in the last six months. On average, patients tended to have an average to above average BMI (mean =26.3, median = 25.0). However, many patients also experienced a high rate of unintended weight loss (11.8% with >11lb weight loss in the last 6 months). Cytopenias were also frequently encountered, with 14.7% of participants having required previous transfusions. Among these, 46% required transfusions in the last 6 months. Thrombosis (18.3%), hemorrhage (14.7%), and anemia (48.0%) were relatively common. In the last six months, 11.1% of patients required iron supplementation and 2.2% required erythropoietin injections. Many patients also endorsed the use of medications that could contribute to overall fatigue. Correlations. Items significantly correlated with worsened fatigue score (BFI greater than or equal to four) included female gender (<0.001), age (p=0.0047), lower education level (<0.001) and lower BMI (<0.001). Current use of alcohol and tobacco was also significantly associated with greater burden of fatigue (<0.001 and 0.0025, respectively). Items not significantly associated with fatigue included DIPSS (MF only), IPSET (ET only) or PV risk scoring. Conclusions Overall patients with MPN experience an exclusive pattern of disabling fatigue. Many fatigue-related medications and medical comorbidities may contribute to the debilitating fatigue seen among MPN patients, although no specific comorbidities could account for the high prevalence of fatigue. Rates of comorbid disease burden varied widely compared to the general population. For some diseases including diabetes, rates among MPN populations were less than the general population (National Diabetes Statistics Report, 2014), however the rates of other comorbidities, such as hypothyroidism, were higher (J Clin Endocrinol Metab 2002;87:489–99). Similar to our previous studies, females tended to suffer from a higher mean fatigue burden than males (Geyer ASH 2014). Clinical and research-related determination of fatigue should take into account cofounding comorbid medical conditions that can contribute to overall fatigue burden. Disclosures Harrison: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; CTI: Consultancy; YM Bioscience: Consultancy; Gilead: Consultancy; SBio: Consultancy. Mesa:Incyte: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; Ns Pharma: Research Funding; Celgene: Research Funding; Lilly: Research Funding; Cti: Research Funding.

BACKGROUND Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS A 70‐item, Internet‐based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index ( P <.001), current use of alcohol ( P <.001), and current tobacco use ( P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week ( P <.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome ( P = .006), diabetes mellitus ( P = .045), fibromyalgia ( P < 0.001), chronic fatigue syndrome ( P = .006), and chronic kidney disease ( P = .02). Current use of antidepressants ( P <.001), antihistamines ( P = .0276), antianxiety medications ( P = .0357), and prescription pain medications ( P <.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms ( P <.0001). CONCLUSIONS The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. Cancer 2016;122:477–485. © 2015 American Cancer Society .