Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis.

Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse.

Interferons in the treatment of myeloproliferative neoplasms.

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.

A review of what interferons are and how they are used in the treatment of the myeloproliferative neoplasms polycythemia vera, essential thrombocythemia, and primary myelofibrosis Why was this paper written? This paper was written to summarize the current clinical landscape of the use of interferons for the treatment of myeloproliferative neoplasms (MPN). What are interferons and how are they used in MPNs? Interferons are small proteins involved in cellular signaling that have been used to treat MPNs, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), for more than 35 years. They can have modulatory effects on the immune system and on the fundamental causes of disease. The use of interferons as treatment was initially limited due to difficulties with their administration and the potential for significant adverse effects. Many of these shortcomings were addressed by chemically binding a biocompatible polymer, polyethylene glycol (PEG), to the structure of the interferon, which increases the stability of the protein, prolongs the time during which it is active, and reduces negative effects to the immune system. The combined chemical structure of PEG and interferon (pegylated interferon or peginterferon) is recommended for use in the treatment of PV, ET, and PMF. What topics are discussed in this paper? In this review paper we evaluate the clinical effectiveness and safety of two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi) and discuss the practical clinical management of interferon-based therapies, along with the authors' opinions on whether to and how to switch therapy from hydroxyurea. Key topics and questions related to the use of interferons, such as their safety and tolerability, the significance of their effects on mutated cells, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. What do the findings mean? Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results.

ABSTRACT: Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, then 5 mg once daily thereafter (all-daily dosing; n = 42). Proportion of patients achieving a ≥10% decrease in spleen volume at 12 weeks was 28% for daily-to-weekly dosing and 59.5% for all-daily dosing. Proportions of patients achieving ≥50% decrease at week 12 in Myelofibrosis Symptom Assessment Form and Myeloproliferative Neoplasms Symptom Assessment Form symptom scores were 14% and 18% for daily-to-weekly dosing, and 28% and 32% for all-daily dosing, respectively. Most common nonhematologic treatment-emergent adverse events were nausea (23%), diarrhea (22%), abdominal pain and fatigue (each 19%), and cough and dyspnea (each 18%). New-onset grade 3 and 4 thrombocytopenia were observed in 19% of patients, each dosed daily-to-weekly, and in 26% and 7% of patients dosed all-daily, respectively, managed with dose interruptions. Hemoglobin levels remained steady. The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib. This trial was registered at www.clinicaltrials.gov as #NCT02718300.

In-Hospital and readmission outcomes of patients with myeloproliferative neoplasms and atrial fibrillation: insights from the National Readmissions Database.

INTRODUCTION: Patients with myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) are at increased risk of thrombosis and bleeding. However, the risk of thrombosis and bleeding in patients with AF and MPN compared with the general population with AF is unclear. Additionally, traditional risk scores (CHA2DS2-VASC and HAS-BLED) for risk/benefit estimation of thromboprophylaxis in AF do not account for MPN status. Therefore, we aimed to investigate bleeding and thrombosis risk in patients with MPN hospitalized for AF. METHODS: We utilized the National Readmission Database (NRD) to identify patients with AF with and without MPN. Primary bleeding and thrombosis outcomes were in-hospital or 30-day readmission for bleeding or thrombosis, respectively. We propensity score (PS) matched patients with and without MPN. Risk of primary outcomes in MPN was assessed in PS matched cohort using logistic regression. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of primary thrombosis and bleeding outcomes, respectively. RESULTS: 24,185 patients without MPN were matched with 1,617 patients with MPN and variables were balanced between groups. Patients with MPN were at increased risk of meeting the thrombosis (OR 1.98, 95% CI 1.23-3.21) but not bleeding (OR 0.87, 95% CI 0.63-1.19) primary outcomes. In MPN, CHA2DS2-VASC predicted thrombosis (C-statistic 0.66, 95% CI 0.54-0.78) but HAS-BLED was a poor predictor of bleeding (C-statistic 0.55, 95% CI 0.46-0.64). CONCLUSION: In patients with AF, MPN was associated with increased risk of bleeding and thrombosis. HAS-BLED scores did not accurately predict bleeding in MPN. Further investigation is needed to refine risk scores in MPN.

Outcomes of Patients With Myeloproliferative Neoplasms Admitted With Myocardial Infarction: Insights From National Inpatient Sample.

Background: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell neoplasms with a high risk of thrombosis, including acute myocardial infarction (AMI). However, outcomes after AMI have not been thoroughly characterized. Objectives: The purpose of this study was to characterize outcomes after AMI in patients with MPNs compared with patients without MPNs. Methods: Patients with a primary admission of AMI from January 2006 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest included in-hospital death or cardiac arrest (CA) and major bleeding. Propensity score weighting was used to compare outcomes between MPN and non-MPN groups. Results: A total of 1,644,304 unweighted admissions for AMI were included; of these admissions, 5,374 (0.3%) were patients with MPNs. After propensity score weighting, patients with MPNs had a lower risk of in-hospital death or CA (OR: 0.83; 95% CI: 0.82-0.84) but a higher risk of major bleeding (OR: 1.29; 95% CI: 1.28-1.30) compared with non-MPN patients. There was a decreasing temporal rate of in-hospital death or CA and bleeding in patients without MPNs (Ptrend < 0.001 for both). However, there was an increasing temporal rate of in-hospital death or CA (Ptrend < 0.001) and a stable rate of major bleeding (Ptrend = 0.48) in patients with MPNs. Conclusions: Among patients hospitalized with AMI, patients with MPNs have a lower risk of in-hospital death or CA compared with patients without MPNs, although they have a higher risk of bleeding. More investigation is needed in order to improve post-AMI bleeding outcomes in patients with MPN.

Anxiety exacerbation in a patient with chronic myeloid leukemia receiving dasatinib and venlafaxine.

INTRODUCTION: Tyrosine kinase inhibitor (TKI) use leads to near-normal life expectancy in patients with chronic myeloid leukemia (CML); unfortunately for some patients, adverse drug effects (ADEs) and medication burden associated with TKI therapy can lead to decreased quality of life. Additionally, TKIs have drug interactions that may negatively impact patients' management of co-morbidities or lead to increased ADEs. CASE REPORT: A 65-year-old female with a history of anxiety treated and controlled with venlafaxine experienced increased and resistant anxiety and insomnia after starting dasatinib for CML. MANAGEMENT AND OUTCOME: On dasatinib, the patient experienced worsening anxiety and insomnia. The stress of a new leukemia diagnosis, drug interactions, and ADEs from dasatinib were considered possible causes. Dose adjustments to dasatinib and venlafaxine were made to control the patient's symptoms. However, the patient's symptoms did not resolve. After being on dasatinib for 2.5 years, the patient discontinued TKI therapy due to being in a deep molecular remission and given ongoing challenges managing anxiety. Within 4 months of stopping dasatinib, the patient reported an improvement in anxiety and overall emotional wellbeing. She continues to feel better and remains in a complete molecular remission 20 months off treatment. DISCUSSION: This case demonstrates a possible previously unknown drug interaction with dasatinib as well as a possible rarely reported ADE of dasatinib. Additionally, it highlights the difficulties patients with psychiatric disorders may face on TKI therapy and challenges providers may have in identifying rare psychiatric ADEs, thus emphasizing the need for documentation of these types of cases.

Risk Factors for Death or Cardiovascular Events after Acute Coronary Syndrome in Patients with Myeloproliferative Neoplasms.

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of cardiovascular disease (CVD), including acute coronary syndrome (ACS). However, data on long-term outcomes of patients with MPN who have had ACS and risk factors for all-cause death or CV events post-ACS hospitalization are lacking. We conducted a single-center study of 41 consecutive patients with MPN with ACS hospitalization after MPN diagnosis. After a median follow-up of 80 months after ACS hospitalization, 31 (76%) experienced death or a CV event (myocardial infarction, ischemic stroke, or heart failure hospitalization). After multivariable Cox proportional hazards regression, index ACS within 12 months of MPN diagnosis (HR 3.84, 95% CI 1.44-10.19), WBC ≥ 20 K/µL (HR 9.10, 95% CI 2.71-30.52), JAK2 mutation (HR 3.71, 95% CI 1.22-11.22), and prior CVD (HR 2.60, 95% CI 1.12-6.08) were associated with increased death or CV events. Further studies are warranted to improve cardiovascular outcomes in this patient population.

Consensus recommendations on peripheral blood smear review: defining curricular standards and fellow competency.

Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely review peripheral blood smears (PBS) in providing clinical care. Competency in PBS review at graduation is required by the ACGME. However, there are no consensus guidelines on best practices surrounding PBS review, education, or competency. We describe the generation of proposed theory and the consensus recommendations developed through a multi-institutional focus group, developed using constructivist grounded theory and a modified nominal group technique. Eight academic hematologists, spanning classical and malignant hematology, enrolled and participated in 2 one-hour focus groups. All routinely worked with fellows and half had formally instructed trainees on PBS interpretation. Focus group data were analyzed using mixed-methods techniques. Tenets of emerging theory were identified through inductive coding. Consensus recommendations (CR) were generated. Participants reviewed CR in an iterative fashion until consensus was reached. Strong consensus was reached on multiple aspects of PBS education. All agreed that trainees should learn PBS review through a systematic approach. Group discussion focused on disorders of red and white blood cells. The diagnoses of acute leukemia and thrombotic microangiopathies were most commonly discussed, with specific emphasis on disorders in which prompt recognition was required to avert significant patient morbidity. These CR offer external validity to future research and curricular development for both PBS review and other visuospatial tasks in medical education.

Psychological mobile app for patients with acute myeloid leukemia: A pilot randomized clinical trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) experience a substantial decline in quality of life (QoL) and mood during their hospitalization for intensive chemotherapy, yet few interventions have been developed to enhance patient-reported outcomes during treatment. METHODS: We conducted a pilot randomized trial (ClinicalTrials.gov identifier NCT03372291) of DREAMLAND, a psychological mobile application for patients with a new diagnosis of AML who are receiving intensive chemotherapy. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND included four required modules focused on: (1) supportive psychotherapy to help patients deal with the initial shock of diagnosis, (2) psychoeducation to manage illness expectations, (3) psychosocial skill-building to promote effective coping, and (4) self-care. The primary end point was feasibility, which was defined as ≥60% of eligible patients enrolling and 60% of those enrolled completing ≥60% of the required modules. We assessed patient QoL (the Functional Assessment of Cancer Therapy-Leukemia), psychological distress (the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9), symptom burden (the Edmonton Symptom Assessment Scale), and self-efficacy (the Cancer Self-Efficacy Scale) at baseline and at day 20 after postchemotherapy. RESULTS: We enrolled 60 of 90 eligible patients (66.7%), and 62.1% completed ≥75% of the intervention modules. At day 20 after chemotherapy, patients who were randomized to DREAMLAND reported improved QoL scores (132.06 vs. 110.72; p =.001), lower anxiety symptoms (3.54 vs. 5.64; p = .010) and depression symptoms (Hospital Anxiety and Depression Scale: 4.76 vs. 6.29; p = .121; Patient Health Questionnaire-9: 4.62 vs. 8.35; p < .001), and improved symptom burden (24.89 vs. 40.60; p = .007) and self-efficacy (151.84 vs. 135.43; p = .004) compared with the usual care group. CONCLUSIONS: A psychological mobile application for patients with newly diagnosed AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QoL, mood, symptom burden, and self-efficacy.

Predictors of increased risk of adverse cardiovascular outcomes among patients with myeloproliferative neoplasms and atrial fibrillation.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), have increased risk of cardiovascular (CV) disease. Atrial fibrillation (AF) is associated with adverse CV outcomes including arterial thrombosis, heart failure (HF), and CV death and coexists with MPN. Traditional risk scores (CHA2DS2-VASC and HAS-BLED) for estimating risks/benefits of anticoagulation to prevent thrombotic events in AF do not include MPN status. Therefore, we aimed to investigate CV outcomes in patients with MPN and AF and evaluate the predictive ability of traditional risk scores. METHODS: We conducted a single-center, retrospective cohort study of patients with MPN and AF. Primary outcome was composite of CV death and arterial thromboembolism; secondary outcomes were bleeding requiring emergency department visit or hospitalization, hospitalization for HF, and all-cause death. Multivariable competing-risk and Cox proportional hazards regression models were used to estimate risk of outcomes. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of composite outcome and bleeding, respectively. RESULTS: A total 142 patients was included (62 ET, 54 PV, 26 MF). Composite outcome, bleeding, HF hospitalization and all-cause death occurred in 39 %, 30 %, 34 %, and 48 %, of patients respectively. After multivariable modeling, MF was associated with increased risk of composite outcome (SHR 2.70, 95 % CI 1.38-5.27) and all-cause mortality (HR 9.77, 95 % CI 4.88-19.54) but not bleeding (SHR 1.19, 95 % CI 0.51-2.80) or HF admissions (SHR 0.57, 95 % CI 0.19-1.72). CHA2DS2-VASC and HAS-BLED were poor predictors of composite outcome (C-statistic 0.52, 95 % CI 0.43-0.62) and bleeding (C-statistic 0.49, 95 % CI 0.40-0.58), respectively. CONCLUSION: In patients with MPN and AF, MF is associated with increased risk of CV death and arterial thrombosis and traditional risk scores do not accurately predict outcomes in this patient population. Further investigation is needed to refine risk scores in this patient population.

Incidence of bleeding events in patients on concomitant tyrosine kinase inhibitors and selective serotonin reuptake inhibitors.

INTRODUCTION: In this study, we aim to determine the risk of bleeding or thrombosis with concurrent use of tyrosine kinase inhibitors (TKIs) used to treat CML, and serotonin reuptake inhibitors (SSRIs). METHODS: We conducted a retrospective cohort study of patients with CP-CML cared for at Massachusetts General Hospital (MGH) between April 2016 to February 2021. Participants were included if diagnosed with CP-CML and began TKI treatment (imatinib, dasatinib, nilotinib, bosutinib, or ponatinib) after April 2016. RESULTS: One hundred patients were evaluated, eighty of whom were taking TKIs only (median age 55, 40% female), and twenty were taking TKI and SSRI concomitantly (median age 53.5, 55% female). Baseline demographics between these groups were similar across all variables. Patients in the TKI only group had 9 bleeding events and 3 thrombotic events. Patients in the combination group had 6 bleeding events and 1 thrombotic event. There was no difference between overall rates of major bleeding (4% v. 10%, p = 0.26) or thrombotic events (4% v. 5%, p = 1). However, patients in the combination group were more likely to have major intracranial bleeding events (0% v. 10%, p = 0.04), and there was a trend to significance for minor bleeding events (7.5% v. 20%, p = 0.11). CONCLUSIONS: Concomitant use of TKIs and SSRIs does not appear to increase the total risk of bleeding or thrombotic events compared to patients on TKIs only. However, concomitant use of TKIs and SSRIs may increase risk of intracranial bleeding. Further work is needed to fully assess this risk.

Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease.

Cardiovascular events and hematologic progression to myelofibrosis or leukemia are leading causes of morbidity and mortality among patients with myeloproliferative neoplasms (MPN). Pulmonary hypertension (PH) is also associated with MPN and cardiovascular disease (CVD), though its prognostic significance in MPN is not well characterized. Our primary objective was to investigate the effect of PH, defined as right-ventricular systolic pressure (RVSP) ≥ 50 mmHg on echocardiogram or mean pulmonary artery pressure (mPAP) ≥ 20 on right heart catheterization, on cardiovascular and all-cause mortality and hematologic progression in patients with MPN and CVD (atrial fibrillation, heart failure hospitalization, and myocardial infarction after MPN diagnosis). Of the 197 patients included (86 ET, 80 PV, 31 PMF), 92 (47%) had PH and 98 (50%) were male. All-cause mortality (58 vs 37%, p = 0.004), cardiovascular death (35 vs 9%, p < 0.0001), and hematologic progression (23 vs 11%, p = 0.037) occurred more frequently in patients with PH. Multivariable competing-risk and proportional hazards regression showed that PH was associated with increased risk of all-cause death (adjusted hazard ratio [HR], 1.80, 95% CI 1.10-2.93), CV death (adjusted subdistribution HR 3.71, 95% CI 1.58-8.73), and hematologic progression (adjusted subdistribution HR 1.99, 95% CI 1.21-3.27).

In-Hospital and readmission outcomes of patients with myeloproliferative neoplasms and heart failure: Insights from the National Readmissions Database.

Background: Myeloproliferative neoplasms (MPNs) are chronic leukemias associated with increased risk of cardiovascular (CV) events. Prior studies suggest patients with MPN are at increased risk of HF. Additionally, pre-clinical murine models harboring the JAK2 mutation, the most common driver mutation in MPNs, have shown accelerated adverse cardiac remodeling in myocardial infarction and pressure overload HF models. However, clinical outcomes, including in-hospital and readmission outcomes, of patients with MPN admitted for HF have not been well characterized. Methods: Patients hospitalized for HF with and without MPN were identified using the 2017 and 2018 National Readmission Database. Propensity score matching (PSM) was performed to match 1 MPN with 10 non-MPN controls. Outcomes were in-hospital death, 90-day CV-related, HF-related, and all-cause readmissions. Logistic regression and Cox proportional hazards regression models were used to estimate risk of in-hospital death and 90-day readmission outcomes, respectively. Results: After PSM, 4,626 patients with MPN were matched with 46,260 without. Patients with MPN were associated with increased risk of in-hospital death (OR 1.17, 95% CI 1.00 - 1.35), 90-day CV-related (HR 1.10, 95% CI 1.02 - 1.18) and all-cause (HR 1.24, 95% CI 1.17 - 1.31) but not HF-related (HR 1.05, 95% CI 0.97 - 1.14) readmissions. Conclusion: Among patients hospitalized for HF, MPN was associated with increased risk of in-hospital death, and 90-day CV-related readmissions (driven primarily by thrombotic readmissions). Further investigation is needed in order to improve outcomes in patients with MPN and HF.

Interferons as the First Choice of Cytoreduction in Essential Thrombocythemia and Polycythemia Vera.

Interferons are cytokines with immunomodulatory properties that have been used in the treatment of myeloproliferative neoplasms (MPNs) for decades. However, their widespread use has been hampered by their adverse effect profile and difficulty with administration. Recently there has been a resurgence of interest in the use of interferons in MPNs given the development of pegylated formulations with improved tolerability. Currently, treatments for polycythemia vera (PV) and essential thrombocythemia (ET) are targeted toward decreasing the risk of thrombotic complications, because there are no approved therapies that are known to modify disease. However, recent data on interferons in MPNs have suggested the potential for disease-modifying activity, including the achievement of molecular remission and sustained clinical response. This development has led to the question of whether interferons should move forward as the preferred frontline cytoreductive agent for ET and PV, and challenges the criteria currently used to initiate therapy. We review randomized controlled trial data evaluating interferon's efficacy and tolerability in patients with ET and PV. We then consider the data in the context of interferon's known advantages and disadvantages to address whether interferons should be the first choice for cytoreductive treatment in patients with ET and PV.

Myeloproliferative Neoplasms, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.