Mesa, Ruben A.

Key Points Germ line variants in TERT, SH2B3, TET2, ATM, CHEK2, PINT, and GFI1B are associated with JAK2 V617F clonal hematopoiesis and MPNs. Age-related JAK2 V617F clonal hematopoiesis is found in ∼2 out of 1000 individuals in the general population.

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 .

AbstractObjectivesPolycythemia vera (PV)‐related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant.MethodsIn the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient‐reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN‐SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC).ResultsCompared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ‐C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10‐point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN‐SAF symptom scores were consistent with improvements in EORTC QLQ‐C30, PSIS, and PGIC scores.ConclusionsRuxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant.

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.

AbstractBackground: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown.Methods: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare. RR and 95% confidence intervals (CI) were estimated utilizing Cox proportional hazard regression.Results: After &gt;250,000 person-years of follow-up, 257 cases of MPN were identified (172 ET, 64 PV). Ever use of hormone therapy (HT) was associated with an increased risk of ET (RR = 1.63; 95% CI, 1.19–2.23) but a decreased risk of PV (RR = 0.58; 95% CI, 0.34–0.98). There were no statistically significant associations of oral contraceptives or reproductive factors with MPN risk overall, or by MPN subtype. Bilateral oophorectomy was associated with increased risk of ET (RR = 1.58; 95% CI, 1.11–2.25) and decreased risk of PV (RR = 0.32; 95% CI, 0.12–0.88). There was no association of ovulatory years with ET risk; however, there was increased risk of PV (RR = 1.68 for &gt;36.8 compared with ≤27.6 years; P trend = 0.045). Adjustment for potential confounding factors did not alter these associations.Conclusions: HT use and bilateral oophorectomy had opposite associations for ET and PV. Except for ovulatory years and PV risk, reproductive history did not appear to play a role in the etiology of MPN.Impact: This study suggests different mechanistic impacts of estrogen, and perhaps distinct etiologies, for the two major MPN subtypes. Cancer Epidemiol Biomarkers Prev; 25(1); 151–7. ©2015 AACR.