Scherber, Robyn M.

Summary Rapid advances in the understanding of the molecular biology, data from translational and clinical trials, and retrospective analyses has influenced the diagnosis and treatment of systemic mastocytosis ( SM ). Many options have existed for the symptomatic management of SM patients, but recent evolution in regards to the molecular underpinnings of this disease and our ability to distinguish clonal mastocytosis from mast cell activation syndrome has changed our treatment paradigm and opened new opportunities for understanding genetic risk, transformation to mast cell leukaemia, and treatment choices. Key to this change has been the discovery of the KIT mutation and the use of next generation sequencing to evaluate for co‐existing molecular mutations that may define the disease course. Careful diagnosis, judicious symptom management and close surveillance of those who may have yet undiagnosed disease is paramount in providing optimal management. In this article, we review the diagnosis and provide a paradigm for the management of SM patients.

Key Points After hydroxycarbamide therapy in high-risk ET, ruxolitinib showed no improvement for complete or partial response rates compared with BAT. Ruxolitinib significantly improved some disease-related symptoms, but rates of thrombosis, hemorrhage, or transformation were not different.

BACKGROUNDPatients 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.METHODSA 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.RESULTSOverall, 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.ConclusionsThe 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.

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 .

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.