Depressive symptoms and myeloproliferative neoplasms: Understanding the confounding factor in a complex condition.

BACKGROUND: Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, have severe function-limiting symptom burden that is experienced by the majority of patients. Previous studies have suggested that depression may be present in over a quarter of MPN patients, but to date no studies have evaluated the relationship between depression and other variables such as symptoms. METHODS: A 70-item internet based survey regarding fatigue and mood symptoms was developed by a multidisciplinary team of MPN investigators, patients and patient advocates including Patient Health Questionnaire and the Myeloproliferative Neoplasm Symptom Assessment Form was completed by over 1300 patients with MPN diagnosis. RESULTS: There were 309 respondents (23%) with PHQ-2 scores ≥ 3. In this analysis, we found worse systemic symptom burden in individuals reporting depressive symptoms. CONCLUSION: This analysis suggests the importance of depression in contributing to as well as confounding symptomatology in MPN patients, and suggests that this critical variable should also be addressed by clinicians and researchers alike when comprehensively assessing symptom burden etiologies.

Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group.

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.

The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: An analysis by the MPN QOL International Study Group.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. CONCLUSIONS: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society.

Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease.

PURPOSE: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden. PATIENTS AND METHODS: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly). RESULTS: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S). CONCLUSION: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms.

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.