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Abstract Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor–naive patients from SIMPLIFY‐1 (NCT01969838), a double‐blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1‐grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.

Abstract Alleviating symptom burden in patients with myeloproliferative neoplasms (MPNs) is imperative to achieving optimal management. Research remains to elucidate the relationship between the JAK2V617F (Janus kinase 2) mutation present in many MPN patients, and the symptomatology they experience. This retrospective study analysed data collected from MPN patients included in the Myeloproliferative Neoplasms: An In‐depth Case–Control (MOSAICC) pilot study. The MPN Symptom Assessment Form was administered, and median symptom scores were compared between JAK2V617F‐positive and JAK2V617F‐negative groups. Multivariate logistic regression analysis adjusted for confounding variables. Overall, 106 MPN patients participated: 65.1% were JAK2V617F positive, 30.2% were JAK2V617F negative and 4.7% had an unknown status. Multivariate analysis revealed a low symptom burden for early satiety (p

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

[This corrects the article DOI: 10.1371/journal.pone.0278354.].

The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts

Abstract The safety profile of the novel oral JAK2/IRAK1 inhibitor pacritinib in patients with cytopenic myelofibrosis was described in the Phase 2 PAC203 and Phase 3 PERSIST‐2 studies. To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk‐adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia.

Pentraxin 2 (PTX-2; serum amyloid P component), a circulating endogenous regulator of the inflammatory response to tissue injury and fibrosis, is reduced in patients with myelofibrosis (MF). Zinpentraxin alfa (RO7490677, PRM-151) is a recombinant form of PTX-2 that has shown preclinical antifibrotic activity and no dose-limiting toxicities in phase I trials. We report results from stage 1 of a phase II trial of zinpentraxin alfa in patients with intermediate-1/2 or high-risk MF. Patients (n=27) received intravenous zinpentraxin α weekly (QW) or every 4 weeks (Q4W), as monotherapy or an additional therapy for patients on stable-dose ruxolitinib. The primary endpoint was overall response rate (ORR; investigatorassessed) adapted from International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria. Secondary endpoints included modified Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) change, bone marrow (BM) MF grade reduction, pharmacokinetics, and safety. ORR at week 24 was 33% (n=9/27) and varied across individual cohorts (QW: 38% [3/8]; Q4W: 14% [1/7]; QW+ruxolitinib: 33% [2/6]; Q4W+ruxolitinib: 50% [3/6]). Five of 18 evaluable patients (28%) experienced a ≥50% reduction in MPN-SAF TSS, and six of 17 evaluable patients (35%) had a ≥1 grade improvement from baseline in BM fibrosis at week 24. Most treatment-emergent adverse events (AE) were grade 1–2, most commonly fatigue. Among others, anemia and thrombocytopenia were infrequent (n=3 and n=1, respectively). Treatment-related serious AE occurred in four patients (15%). Overall, zinpentraxin alfa showed evidence of clinical activity and tolerable safety as monotherapy and in combination with ruxolitinib in this open-label, non-randomized trial (clinicaltrials gov. Identifier: NCT01981850).

This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas. The population-based cohort study used Texas Cancer Registry data (1995–2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses. The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0–19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15–19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01–1.26] for all cancer types. Comparing to patients diagnosed at ages 1–4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36–2.09), at 10–14 year (HR: 1.42, 95% CI: 1.20–1.68), or at 15–19 years (HR: 1.40, 95% CI: 1.20–1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer. South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age

BackgroundTo address the unmet need for a commercial cancer-specific meditation app, we leveraged a long-standing partnership with a consumer-based app (ie, Calm) to develop the first commercial meditation app prototype adapted specifically for the needs of patients with cancer. Input was obtained at both the individual user and clinic levels (ie, patients with and survivors of cancer and health care providers). ObjectiveThis study aimed to determine the feasibility of a cancer-specific meditation app prototype. MethodsPatients with and survivors of cancer who were recruited and enrolled in the feasibility randomized controlled trial were asked to use the prototype app daily (≥70 minutes per week) for 4 weeks. Participants completed web-based weekly questionnaires and a final poststudy questionnaire and were asked to participate in an optional web-based poststudy interview. The questionnaires and interviews covered the following feasibility categories: acceptability, demand, practicality, and adaptation. ResultsA total of 36 patients with and survivors of cancer completed the baseline questionnaire, 18 completed the final questionnaire, and 6 completed the optional interviews. Weekly and poststudy questionnaires indicated high overall enjoyment, ease of use, and satisfaction with the app content, aesthetics, and graphics. The objective use data indicated that the average total app use rate was 73.39 (SD 7.12) minutes per week. Interviews (N=6) revealed positive and mixed responses to the app prototype and informative differences related to preferences for narrators, emotional content, and meditation teaching but an overall appreciation for the variety of options. ConclusionsThe most likely candidates for moving from cancer-specific meditation apps to dissemination are through partnering with the industry, in which name recognition and market distribution are already established (even showing a base of users from the targeted population with cancer). This study established the feasibility of a cancer-specific mobile meditation app prototype for patients with and survivors of cancer, using a commercially available app. The quantitative and qualitative data demonstrated the acceptability, demand, practicality, and adaptation of the prototype. Improvements suggested by the participants will be considered in the final app design before testing the efficacy of the app in a future study. Trial RegistrationClinicaltrials.gov NCT05459168; https://clinicaltrials.gov/ct2/show/record/NCT05459168

BackgroundTo address the need for long-term, accessible, nonpharmacologic interventions targeting sleep in patients with chronic hematological cancer, we propose the first randomized controlled trial to determine the effects of a consumer-based mobile meditation app, Calm, on sleep disturbance in this population. ObjectiveThis study aims to test the efficacy of daily meditation delivered via Calm compared with a health education podcast control group in improving the primary outcome of self-reported sleep disturbance, as well as secondary sleep outcomes, including sleep impairment and sleep efficiency; test the efficacy of daily meditation delivered via Calm compared with a health education podcast control group on inflammatory markers, fatigue, and emotional distress; and explore free-living use during a 12-week follow-up period and the sustained effects of Calm in patients with chronic hematological cancer. MethodsIn a double-blinded randomized controlled trial, we will recruit 276 patients with chronic hematological cancer to an 8-week app-based wellness intervention—the active, daily, app-based meditation intervention or the health education podcast app control group, followed by a 12-week follow-up period. Participants will be asked to use their assigned app for at least 10 minutes per day during the 8-week intervention period; complete web-based surveys assessing self-reported sleep disturbance, fatigue, and emotional distress at baseline, 8 weeks, and 20 weeks; complete sleep diaries and wear an actigraphy device during the 8-week intervention period and at 20 weeks; and complete blood draws to assess inflammatory markers (tumor necrosis factor-α, interleukin-6, interleukin-8, and C-reactive protein) at baseline, 8 weeks, and 20 weeks. ResultsThis project was funded by the National Institutes of Health National Cancer Institute (R01CA262041). The projects began in April 2022, and study recruitment is scheduled to begin in October 2022, with a total project duration of 5 years. We anticipate that we will be able to achieve our enrollment goal of 276 patients with chronic hematological cancers within the allotted project time frame. ConclusionsThis research will contribute to broader public health efforts by providing researchers and clinicians with an evidence-based commercial product to improve sleep in the long term in an underserved and understudied cancer population with a high incidence of sleep disturbance. Trial RegistrationClinicalTrials.gov NCT05294991; https://clinicaltrials.gov/ct2/show/NCT05294991 International Registered Report Identifier (IRRID)PRR1-10.2196/39007

Abstract 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.

BackgroundMyeloproliferative neoplasms (MPNs) are a group of myeloid malignancies associated with significant symptom burden. Despite pharmacological advances in therapies, inadequate management of MPN symptoms results in reduced quality of life. ObjectiveThis study aims to determine the feasibility of a 12-week global wellness mobile app intervention in decreasing MPN symptom burden. The University of Arizona Andrew Weil Center for Integrative Medicine’s global wellness mobile app, My Wellness Coach (MWC), guides patients to improve their health and well-being through facilitating behavior changes. MethodsOf the 30 patients enrolled in a 12-week intervention, 16 (53%) were retained through the final assessment. Feasibility was assessed by the ease of recruitment, participant adherence, and mobile app acceptability. App acceptability was measured using the user version of the Mobile Application Rating Scale. MPN symptom burden was measured at baseline and 12 weeks after the intervention. ResultsRecruitment was efficient, with the participant goal reached within a 60-day period, suggestive of a demand for such an intervention. Adherence was less than the target within study design (75%), although similar to mobile device app use in other studies (53%). The app was deemed acceptable based on the mean user version of the Mobile Application Rating Scale 3-star rating by participants. Finally, there were statistically significant improvements in several MPN symptoms, quality of life, and total score on the Myeloproliferative Neoplasm Symptom Assessment Form surveys. ConclusionsOur 12-week intervention with the MWC app was feasible and was associated with a decrease in MPN symptom burden. Further investigation of the MWC app for use as a self-management strategy to reduce the symptom burden in patients with MPN is warranted.

BackgroundMobile meditation apps may offer a long-term, accessible, and effective solution for ongoing symptom management in cancer patients/survivors. However, there are currently no commercial cancer-specific meditation apps that reflect cancer specialist expertise, input from cancer patients/survivors, and features and content specific to cancer patients’/survivors’ needs. ObjectiveThe aim of this study was to gain insight (via surveys, daily journals, and focus groups) from cancer patients/survivors, health care providers, and current subscribers of Calm (a consumer-based mobile meditation app) who were patients/survivors to develop a prototype of a mobile meditation app specifically designed for cancer patients/survivors. MethodsParticipants were recruited via prior partnerships, word-of-mouth referrals, and recruitment posts on Facebook and Instagram. Cancer patients/survivors and health care providers were instructed to download and use the Calm app for at least 10 minutes a day for 7 days, complete an online daily journal for 7 days, and participate in a virtual focus group (one for cancer patients/survivors and one for providers). Current Calm subscribers who were cancer patients/survivors completed an online survey about different aspects of the Calm app and participated in a third virtual focus group. Data were qualitatively analyzed using a combination of deductive and inductive coding. ResultsA total of 27 participants (11 cancer patients/survivors, 10 health care providers, 6 current Calm subscribers) completed the study. Similar themes and subthemes were found across surveys, daily journals, and focus groups, and fell into two major categories, content and functionality, with cancer-specific and noncancer-specific themes identified within each category. The majority of content preferences and suggestions that arose were cancer-specific, such as content related to negative emotions or feelings (eg, anxiety, grief, trauma/posttraumatic stress disorder, fear of recurrence, isolation), positive feelings and finding meaning (eg, gratitude, storytelling, acceptance), scenarios and experiences (eg, waiting, treatment-specific mediations), type and stage of cancer journey, and movement modifications. Some of the noncancer-specific themes under app content included sleep, music, and visualizations. In terms of app functionality, the majority of participants expressed interest in having a section/tab/area of the app that was specifically geared toward cancer patients/survivors. Preferences and suggestions for cancer-specific functionality features included options based on symptoms or journey, being able to communicate with other patients or survivors to share suggestions for specific meditations, and having an emergency toolkit for patients/survivors. ConclusionsFindings from cancer patients/survivors, health care providers, and current Calm subscribers who were patients/survivors to be incorporated into the development of the prototype fell into two major categories: (1) content of the app and (2) functionality of the app. The prototype’s form and function will be pilot-tested among 30 cancer patients/survivors in a 4-week study, and the resulting feasibility data will be used to inform the final app design and an efficacy study.

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts

Abstract Background Myeloproliferative neoplasm (MPN) patients suffer from significant symptoms, inflammation and reduced quality of life. Yoga improves these outcomes in other cancers, but this hasn’t been demonstrated in MPNs. The purpose of this study was to: (1) explore the limited efficacy (does the program show promise of success) of a 12-week online yoga intervention among MPN patients on symptom burden and quality of life and (2) determine feasibility (practicality: to what extent a measure can be carried out) of remotely collecting inflammatory biomarkers. Methods Patients were recruited nationally and randomized to online yoga (60 min/week of yoga) or wait-list control (asked to maintain normal activity). Weekly yoga minutes were collected with Clicky (online web analytics tool) and self-report. Those in online yoga completed a blood draw at baseline and week 12 to assess inflammation (interleukin-6, tumor necrosis factor-alpha [TNF-α]). All participants completed questionnaires assessing depression, anxiety, fatigue, pain, sleep disturbance, sexual function, total symptom burden, global health, and quality of life at baseline, week seven, 12, and 16. Change from baseline at each time point was computed by group and effect sizes were calculated. Pre-post intervention change in inflammation for the yoga group was compared by t-test. Results Sixty-two MPN patients enrolled and 48 completed the intervention (online yoga = 27; control group = 21). Yoga participation averaged 40.8 min/week via Clicky and 56.1 min/week via self-report. Small/moderate effect sizes were generated from the yoga intervention for sleep disturbance (d = − 0.26 to − 0.61), pain intensity (d = − 0.34 to − 0.51), anxiety (d = − 0.27 to − 0.37), and depression (d = − 0.53 to − 0.78). A total of 92.6 and 70.4% of online yoga participants completed the blood draw at baseline and week 12, respectively, and there was a decrease in TNF-α from baseline to week 12 (− 1.3 ± 1.5 pg/ml). Conclusions Online yoga demonstrated small effects on sleep, pain, and anxiety as well as a moderate effect on depression. Remote blood draw procedures are feasible and the effect size of the intervention on TNF-α was large. Future fully powered randomized controlled trials are needed to test for efficacy. Trial registration This trial was retrospectively registered with clinicaltrials.gov (ID: NCT03503838) on 4/19/2018.

Background: Depression, anxiety, and sleep disturbance are common problems that greatly affect quality of life for many myeloproliferative neoplasm (MPN) patients. App-based mindfulness meditation is a feasible nonpharmacologic approach for managing symptoms. However, previous research has not considered how patients’ overall mental health may influence their responsiveness to these interventions. Objective: The purpose of this study was to conduct an exploratory, secondary analysis of the effects of a smartphone meditation app, Calm, on depression, anxiety, and sleep disturbance in MPN patients based on patients’ baseline levels of Global Mental Health (GMH). Methods: Participants (N = 80) were a subset of MPN patients from a larger feasibility study. Patients were enrolled into an intervention (use Calm for 10 minutes daily for 4 weeks) or educational control group. Results: In multilevel models, there were significant 3-way interactions between time, group, and baseline GMH for depression and anxiety symptoms, with participants in the meditation intervention who reported the poorest baseline GMH experiencing the greatest reduction in symptoms over time. For both intervention and control participants, poorer initial GMH was associated with increases in sleep disturbance symptoms over time. Conclusions: Mindfulness meditation apps, such as Calm, may be effective in reducing depression and anxiety symptoms in MPN patients, particularly for those experiencing mental health difficulties. Given the need for accessible tools to self-manage chronic cancer–related symptoms, especially strong negative emotions, these findings warrant larger efficacy studies to determine the effects of app-based meditation for alleviating depression and anxiety in cancer populations.

Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by either primary myelofibrosis, or secondary MF following essential thrombocythemia or polycythemia vera. Historically, therapy has been symptom directed; however, in 2011, the first janus kinase inhibitor (JAK-i) – ruxolitinib – was approved for treatment. This medication was found to be effective in reduction of symptom burden and spleen size; however, the median duration of response is about 3 years. In addition, many patients are intolerant or develop toxicities to ruxolitinib, including patients with anemia, as well as thrombocytopenia. Therefore, there is a critical need for alternate therapeutic options for patients with MF. Additional JAK-i have been developed over the last 8 years, including fedratinib, momelotinib, and pacritinib. Fedratinib recently received approval for treatment of MF both in the first-line and second-line setting. It has shown efficacy in the first-line setting, as well as in 30% of patients who are refractory/intolerant of ruxolitinib. This review covers the trials that have led to the approval of ruxolitinib as well as fedratinib, as well as reviews of two JAK inhibitors that are still under clinical investigation: momelotinib and pacritinib.

Abstract Background Patients with the myeloproliferative neoplasms (MPNs) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are at increased risk for thrombotic and cardiovascular events and experience a variety of burdensome symptoms. However, there is a paucity of data in the biomedical literature about how MPNs impact productivity in the workplace. This analysis of the Living with MPNs survey was conducted to evaluate the impact of MPNs on employment, career potential, and work productivity. Methods This cross-sectional online survey included respondents aged 18–70 years living in the United States with a diagnosis of MF, PV, or ET. The survey consisted of ~ 100 questions related to MPN diagnosis, disease-related medical history, MPN-related symptoms and functional status, changes in employment and work productivity, and impact on daily activities since diagnosis. The MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) was used to assess symptom burden. The Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP) was used to assess the effects of MPNs on work productivity and activity (7-day recall) among currently employed respondents. Correlations between MPN-SAF TSS and WPAI-SHP scores were calculated using Spearman’s coefficients. Results Of 904 respondents, 592 were employed (MF, n = 174; PV, n = 248; ET, n = 170) at the time of their MPN diagnosis. Approximately half (50.5%) of the 592 employed survey respondents reported ≥1 change in employment status because of their diagnosis, most commonly “left a job” (30.2%) “went on medical disability leave” (24.8%), and “had reductions in work hours for at least 3 months” (21.8%). Among respondents who remained employed at the time of survey participation (n = 398), mean WPAI-SHP scores were as follows: absenteeism, 6.9%; presenteeism, 27.4%; overall work impairment, 31.1%; and activity impairment, 32.8%. WPAI-SHP scores positively correlated with MPN-SAF TSS (correlation coefficients, 0.37–0.70; P

Abstract. Despite the identification of acquired genetic mutations associated with Myeloproliferative Neoplasms (MPNs) there is a paucity of information relating to modifiable risk factors that may lead to these mutations. The MOSAICC Study was an exploratory case-control study of polycythemia vera (PV), essential thrombocythemia (ET), and Myelofibrosis (MF). MPN patients and population controls (identified by General Practitioners) and non-blood relative/friend controls were recruited from 2 large UK centers. Participants completed a telephone-based questionnaire analyzed by unconditional logistic regression analysis adjusting for potential confounders. Risk factors for MPNs identified included increasing childhood household density [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.16–5.62], low childhood socioeconomic status (OR 2.30, 95%CI 1.02–5.18) and high pack years smoking (OR 2.19, 95%CI 1.03–4.66) and current smoking restricted to JAK2 positive PV cases (OR 3.73, 95%CI 1.06–13.15). Obesity was linked with ET (OR 2.59, 95%CI 1.02–6.58) confirming results in previous cohort studies. Receipt of multiple CT scans was associated with a strongly increased risk of MPN although with wide confidence intervals (OR 5.38, 95%CI 1.67–17.3). Alcohol intake was inversely associated with risk of PV (OR 0.41, 95%CI 0.19–0.92) and ET (OR 0.48, 95%CI 0.24–0.98). The associations with childhood household density, high pack years smoking and alcohol were also seen in multivariate analysis. This is the largest case control study in MPNs to date and confirms the previously reported associations with obesity and cigarette smoking from cohort studies in addition to novel associations. In particular, the role of smoking and JAK2 mutation cases merits further evaluation.

Introduction: As cancer center funds are allocated toward several resources, clinical trial offices and the clinical trial infrastructure is constantly scrutinized. It has been shown that 20% of clinical trials fail to achieve their accrual goal and in an institutional level several trials are open with poor accrual. We sought to identify factors that are associated with clinical trial accrual and develop a model to predict clinical trial accrual Methods and material: We identified all clinical trials from 1999 to 2015 at UT Health Cancer Center San Antonio. We included observational as well as interventional clinical trials. We collected several variables such as type of study, type of malignancy, trial phase, PI of study. Results: In total we included 297 clinical trials. We identified several factors to be associated with clinical trial accrual (Sponsor type, trial phase, disease category, type of trial, disease state and whether the trial involved a new investigational agent). We developed a predictive model with an AUC of 0.65 that showed that observational, interventional, industry-sponsored trials and trials authored by the local PI were more likely to achieve their accrual goal. Conclusion: We were able to identify several factors that were significantly associated with clinical trial accrual. Based on these factors we developed a prediction model for clinical trial accrual. We believe that use of this model can help improve our cancer centers clinical trial portfolio and help in fund allocation. Keywords: Clinical trials, Prediction, Model, Accrual, Cancer center

Myeloproliferative neoplasms (MPNs) are rare hematological malignancies with a significant symptom burden often left unresolved despite recent advances in pharmacological therapy. Yoga is a nonpharmacological strategy that has been shown to improve symptoms in other cancers and may be effective for improving symptoms in MPN patients. Online yoga helps address many of the commonly reported barriers of cancer patients to in-person interventions and may make yoga more accessible to MPNs. An exploration of MPN patient perceptions of participation in online yoga is needed to tailor interventions to patient needs and inform future studies. The purpose of this study was to explore the perceptions of MPN patients participating in a 12-week online yoga intervention. This article represents the combined qualitative interview data from two studies. Participants were asked to complete 60 min/wk of online, home-based yoga and were asked to participate in a 15- to 20-minute phone interview postintervention. The qualitative data was coded in NVivo 11 for content analysis. The total sample included 39 MPN patients. Online yoga was well accepted and liked among these patients. They reported physical (eg, improved sleep, reduced fatigue) and mental (eg, reduced stress) health benefits and liked the convenience of being able to do yoga at home. Online yoga provides a feasible and attractive format through which to deliver a nonpharmacological intervention among MPN patients. Randomized controlled trials are needed to confirm the effects of online yoga on MPN patient symptoms. The qualitative findings presented here help inform the development of these future trials.

Purpose: Essential thrombocythemia, polycythemia vera, and myelofibrosis are rare chronic hematological malignancies known as myeloproliferative neoplasms (MPNs) and are characterized by deregulated myeloid lineage cell production, splenomegaly, and heterogeneous symptom profiles. MPN patients suffer from a significant symptom burden (eg, fatigue, depressive symptoms, early satiety) and an impaired overall quality of life (QoL). Current treatments typically include pharmacological approaches, which may come with additional side effects and may be limited by treatment-associated toxicities (ie, cytopenias). Nonpharmacological approaches such as physical activity may be beneficial for reducing symptom burden and improving QoL. To date, no studies have examined physical activity as a nonpharmacological approach in MPN patients despite preliminary evidence supporting its benefit in other hematological cancers. The purpose of this article is to (1) review the literature related to physical activity and specific hematological cancer subtypes and to (2) make suggestions for future research involving physical activity in MPN patients as a symptom management strategy. Methods: A brief review of studies examining physical activity in leukemias, lymphomas, and myelomas (excluding stem-cell transplant patients) was conducted. Results: There is preliminary evidence to suggest that physical activity may be an effective approach to improve patient-reported outcomes (fatigue, depression, anxiety, sleep), physical fitness (cardiovascular fitness, balance, body composition), and overall QoL in other hematological cancers. Conclusions: Based on encouraging findings in other hematological cancers, future research should examine the feasibility and effectiveness of physical activity in MPN patients.

RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7% vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hematocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea-resistant or intolerant patients with polycythemia vera. This trial was registered at clinicaltrials.gov identifier: 01243944.

Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment.

In the 2008 WHO classification, chronic myeloid malignancies that share both myelodysplastic and myeloproliferative features define the myelodysplastic/myeloproliferative group, which includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ring sideroblasts and thrombocytosis, and myelodysplastic/myeloproliferative unclassified. With the notable exception of refractory anemia with ring sideroblasts and thrombocytosis, there is much overlap among the various subtypes at the molecular and clinical levels, and a better definition of these entities, an understanding of their biology and an identification of subtype-specific molecular or cellular markers are needed. To address some of these challenges, a panel comprised of laboratory and clinical experts in myelodysplastic/myeloproliferative was established, and four independent academic MDS/MPN workshops were held on: 9th March 2013, in Miami, Florida, USA; 6th December 2013, in New Orleans, Louisiana, USA; 13th June 2014 in Milan, Italy; and 5th December 2014 in San Francisco, USA. During these meetings, the current understanding of these malignancies and matters of biology, diagnosis and management were discussed. This perspective and the recommendations on molecular pathogenesis, diagnosis and clinical characterization for adult onset myelodysplastic/myeloproliferative is the result of a collaborative project endorsed and supported by the MDS Foundation.

Essential thrombocythemia is a clonal myeloproliferative neoplasm characterized by an elevated platelet count, the potential for both microvascular and macrovascular sequelae, and a risk for transformation to myelofibrosis or acute myeloid leukemia. A systematic and detailed initial analysis is essential for accurate diagnosis of essential thrombocythemia, as many etiologies are reactive and benign. Once a diagnosis has been made, risk stratification and symptom assessment are vital to guide the subsequent therapy. Treatment may be required in high-risk disease, such as in cases of advanced age or prior thrombotic events. Systemic therapy is aimed at reducing the thrombotic risk and includes daily low dose aspirin and in some patients, cytoreductive therapy. Currently, the first line cytoreductive therapy includes hydroxyurea or pegylated interferon, with a phase III clinical trial underway comparing these two important agents. Anagrelide and clinical trials are reserved for refractory or intolerant patients. Looking to the future, new therapies including Janus kinase 2 (JAK2) and telomerase inhibitors are promising and may become valuable to the treatment armamentarium for those afflicted with essential thrombocythemia.

The Philadelphia negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial vascular and transformative complications. Standard therapy for high-risk disease, particularly in patients that have failed initial therapy, remains controversial. Non-pegylated interferon has previously been shown to be effective in controlling erythrocytosis, thrombocytosis and thrombotic complications, but was found to have poor tolerability and excessive adverse effects. Recently, pegylated interferon alpha-2a was introduced and found to be better tolerated and less toxic than standard interferon. In addition, in recent phase II trials, pegylated interferon alpha-2a therapy was found to induce both hematologic and molecular remissions. We retrospectively analyzed 118 myeloproliferative patients who underwent pegylated interferon alpha-2a treatment. Responses were evaluated by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were analyzed.