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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 >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 >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.

The myeloproliferative neoplasms (MPN) including polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis (PMF) are rare diseases contributing to significant morbidity. Symptom management is a prime treatment objective but current symptom assessment tools have not been validated compared to the general population. The MPN‐symptom assessment form (MPN‐SAF), a reliable and validated clinical tool to assess MPN symptom burden, was administered to MPN patients (n = 106) and, for the first time, population controls (n = 124) as part of a UK case–control study. Mean symptom scores were compared between patients and controls adjusting for potential confounders. Mean patient scores were compared to data collected by the Mayo Clinic, USA on 1,446 international MPN patients to determine patient group representativeness. MPN patients had significantly higher mean scores than controls for 25 of the 26 symptoms measured (P < 0.05); fatigue was the most common symptom (92.4% and 78.1%, respectively). Female MPN patients suffered worse symptom burden than male patients (P < 0.001) and substantially worse burden than female controls (P < 0.001). Compared to the Mayo clinic patients, MPN‐UK patients reported similar symptom burden but lower satiety (P = 0.046). Patients with PMF reported the worst symptom burden (88.3%); significantly higher than PV patients (P < 0.001). For the first time we report quality of life was worse in MPN‐UK patients compared with controls (P < 0.001). Am. J. Hematol. 90:864–870, 2015. © 2015 Wiley Periodicals, Inc.

Key Points Pacritinib reduced myelofibrosis-related splenomegaly and patient symptoms without causing clinically significant myelosuppression. Pacritinib had activity and was well tolerated in patients with preexisting anemia and thrombocytopenia.

AbstractTo evaluate the impact of a patient‐centered symposium as an educational intervention on a broad population of cancer patients. We developed a comprehensive patient symposium. Through voluntary questionnaires, we studied the impact of this cancer symposium on quality of life, cancer‐specific knowledge, and symptom management among cancer patients. Symposium attendees were provided surveys prior to and 3 months following the educational intervention. Surveys included (1) EORTC‐QLQ‐C30; (2) disease understanding tool developed for this conference; (3) validated disease‐specific questionnaires. Changes over time were assessed using McNemar's tests and paired t‐tests for categorical and continuous variables, respectively. A total of 158 attendees completed the pre‐convention survey. Most respondents reported at least “quite a bit” of understanding regarding treatment options, screening modalities, symptomatology, and cancer‐related side effects. Attendees endorsed the least understanding of disease‐related stress, risk factors, fatigue management, and legal issues related to disease/treatment. At 3 months, there was improvement in understanding (12 of 14 areas of self‐reported knowledge especially regarding nutrition, and stress/fatigue management). However, no significant change was seen in QLQ‐C30 functioning, fatigue, pain, or insomnia. A patient symposium, as an educational intervention improves a solid knowledge base amongst attendees regarding their disease, increases knowledge in symptom management, but may be insufficient to impact QoL as a single intervention.

Abstract Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation.

Blood eosinophilia (≥0.5 × 109/l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut‐offs for referral to specialist hematology care. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000–2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable logistic regression to calculate odds ratios (ORs) for the 4‐year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16 × 109/l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above the median eosinophil count. At the 99th percentile, corresponding to an eosinophil count of 0.75 × 109/l, risks of hematological malignancies were increased more than twofold with OR (95% C.I.) of 2.39 (1.91–2.99). Interestingly, risks reached a plateau around an eosinophil count of 1.0 × 109/l. Risks also increased when the eosinophil count approached zero. Here, counts associated relatively more with acute myeloid leukemia and myelodysplastic syndromes whereas counts above 0.16 × 109/l associated more with myeloproliferative neoplasms. Eosinophil counts associate with hematological malignancies and mortality even below the definition of eosinophilia. The observed plateau of risks around 1.0 × 109/l is important for physicians encountering patients with eosinophilia since even mild‐to‐moderate eosinophilia according to traditional definitions confers maximally increased risks of subsequent/subclinical hematological malignancy. Am. J. Hematol. 90:225–229, 2015. © 2014 Wiley Periodicals, Inc.

Abstract Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.