Tag Archives: myeloproliferative neoplasms

Thrombosis May Increase Risk of Cardiovascular Disease, Secondary Cancers in Myeloproliferative Neoplasms

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April 21, 2025

Sarah Dingli, Saubia Fathima, Priyansh Faldu, Naseema Gangat, David Dingli & Ayalew Tefferi

Primary myelofibrosis (PMF) is a myeloid neoplasm that is currently classified in the category of JAK2 mutation-prevalent myeloproliferative neoplasms (JAK2-MPNs) [1]; other members of JAK2-MPNs include essential thrombocythemia (ET) and polycythemia vera (PV). JAK2-MPNs are characterized molecularly by JAK-STAT activating mutations, involving JAK2, CALR, and MPL genes, and morphologically by trilineage myeloid proliferation in the bone marrow (BM) that is accentuated by megakaryocyte proliferation and atypia [2]. Peripheral blood (PB) manifestations of JAK2-MPNs include leukocytosis, thrombocytosis, and/or erythrocytosis while other disease features include splenomegaly, thrombosis, bleeding, microvascular disturbances, pruritus, and constitutional symptoms. Patients with MPN are at risk for premature death and disease progression into a fibrotic or leukemic disease phase [3]. Disease complications in JAK2-MPNs are most severe in PMF where median survival is estimated at 4.4 years and leukemic progression at 9%, at a median follow-up of 3.2 years [4].

Leukocytosis, in general, has long been identified/suspected as a risk factor for a number of disease complications in JAK2-MPNs including overall and leukemia-free survival [5, 6], disease progression [7, 8], thrombosis risk [9,10,11], and extramedullary hematopoiesis [12]. Considering the multicomponent nature of leukocytes, more recent studies in JAK2-MPNs have appropriately looked into the differential prognostic impact of absolute neutrophil (ANC) [13,14,15], monocyte (AMC) [13, 16,17,18,19], and lymphocyte (ALC) counts [13,14,15]. By comparison, fewer studies have reported on the prognostic contribution of absolute basophil (ABC) or eosinophil (AEC) counts in JAK2-MPNs, in general, and in PMF, in particular, not associated with tyrosine kinase fusion genes [20,21,22,23,24]. On the other hand, the prognostic relevance of basophilia in chronic myeloid leukemia (CML) is well established and is taken under consideration in defining accelerated phase CML [25, 26]. In the current study, we utilized a large Mayo Clinic database of patients with PMF in order to describe the prevalence and the clinical, molecular, and prognostic correlates of ABC and AEC.

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Introduction to a How I Treat series on myeloproliferative neoplasms

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April 17, 2025

Jason Gotlib, MD

Like other hematologic malignancies, the management of myeloproliferative neoplasms (MPNs) reflects a dynamic assessment of the grades of clinical evidence to guide the appropriateness of therapeutic interventions. The National Comprehensive Cancer Network and European LeukemiaNet have synthesized these data into risk-stratified guidelines to provide foundational approaches for diagnosing and treating MPNs.1,2 However, the biologic, clinical, and molecular heterogeneity of MPNs, as well as the unique treatment goals of individuals often leads to a melding of data-driven algorithms with personalized care approaches informed by shared decision-making between patients and their physicians. Although this hybrid heuristic may introduce some imprecision in this era of precision medicine, it also recognizes that treatment decisions are not completely fated by the results of a multigene next-generation sequencing panel. This is a common theme running through the following 6 articles featured in this How I Treat series on MPNs:

  • Mary Frances McMullin and Claire N. Harrison, “How I treat patients with low-risk polycythemia vera who require cytoreduction”
  • Lucia Masarova and Helen T. Chifotides, “How I individualize selection of JAK inhibitors for patients with myelofibrosis”
  • Akriti G. Jain and Aaron T. Gerds, “How I treat anemia in myelofibrosis”
  • Deepti H. Radia, “How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm”
  • Andreas Reiter, Georgia Metzgeroth, and Nicholas C. P. Cross, “How I diagnose and treat myeloid/lymphoid neoplasms with tyrosine kinase gene fusions”
  • Alexandre Guy, Pierre-Emmanuel Morange, and Chloé James, “How I approach the treatment of thrombotic complications in patients with myeloproliferative neoplasms”

 

In the first How I Treat article, McMullin and Harrison discuss their approach to the use of cytoreduction in patients with low-risk polycythemia vera (PV).3 For high-risk patients (aged >60 years or history of thrombosis), standard care includes the addition of cytoreduction to the low-risk treatment backbone of low-dose aspirin and phlebotomy. In low-risk PV, progressive splenomegaly, leukocytosis, or thrombocytosis (eg, >1500 × 109/L); high symptom burden (related to PV and/or severe iron deficiency); and persistence of frequent phlebotomy are examples of indications that may justify the use of cytoreduction.1,2 In the last several years, molecular remission, eg, reduction of Janus kinase 2 (JAK2) V617F variant allele fraction, has increasingly animated the conversation between patients and physicians. This shift has likely been accelerated by the encouraging longer-term molecular results with ro-PEG-interferon-α-2b (BESREMi) in the CONTINUOUS-PV/PROUD-PV studies.4,5 Although molecular remission is an intuitively attractive therapeutic goal, it remains to be established whether such deeper responses will ultimately translate into disease modification (eg, reduction in thrombosis, decreased evolution to myelofibrosis [MF] or acute myeloid leukemia, and improved overall survival). Individuals without a conventional indication for cytoreduction (especially younger patients who have a longer survival runway ahead of them), may still wish to seek an active treatment plan. The “if and when” to use cytoreduction in the patient with low-risk PV is a complicated calculus of potential side effects, impact on quality of life, financial toxicity, and a hedge that committing to a long-term treatment program will favorably bend the arc of the disease.

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Advances in Blood Cancer Care for Veterans

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April 16, 2025| Federal Practitioner
Thomas Rodgers, MD

Hematologic malignancies encompass a broad range of distinct cancers, generally categorized as lymphoid (eg, lymphoma), myeloid (eg, leukemia, myelodysplastic syndromes, myeloproliferative neoplasms [MPNs]), and plasma cell neoplasms (eg, multiple myeloma).1 The veteran population is aging; this, in combination with other potential veteran-specific risk factors, is leading to an increased risk of hematologic malignancies.2 Of note, the risk for MPN diagnosis has recently been studied in veterans who served during the Korean, Vietnam, and Persian Gulf War eras.3 In addition, survival trends for different blood cancers, such as lymphoid malignancies, vary among veterans exposed to Agent Orange.4 Conflicting results have been found that point to the importance of future research.4 

Veterans in rural areas face barriers to treatment and clinical trial enrollment due to long travel distances and lack of trial availability, creating what are termed “clinical trial deserts.”5 Teleoncology has become crucial in bridging this gap by improving access to blood cancer treatments and clinical trials.5,6 Novel decentralized trial designs involving telehealth can further expand participation in remote areas.5

Over the past year, there have been advances in the treatment of blood cancers as well as the use of large data sets to better understand cancers trends and new technologies to reduce disparities in access to care.6,7 The availability of greater therapeutic options, new care modalities, and improved risk assessments herald an exciting time in the care of patients with hematologic malignancies, with the expectation that this care will continue to advance through 2025.

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Fedratinib Shows Promise in Long-Term MPN Success With Tolerable Toxicity

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By Hany Elmariah, MD

A phase 1 trial investigated the safety and tolerability of maintenance therapy with the JAK2 inhibitor fedratinib (Inrebic) following allogeneic hematopoietic cell transplant (HCT) for myeloproliferative neoplasms (MPNs) and myelodysplastic syndrome/MPN overlap syndromes.

While HCT offers potential cure for MPNs, posttransplant relapse remains a significant challenge. Fedratinib, effective in myelofibrosis, with a favorable safety profile and oral administration, presents a rational strategy to reduce relapse and potentially prevent graft-vs-host disease (GVHD) while preserving the graft-vs-tumor (GVT) effect.

“Usually with fedratinib, the main toxicities are cytopenia, so low blood counts. We also see a fair amount of [gastrointestinal (GI)] toxicity, nausea, vomiting, or diarrhea,” said Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the Department of Bone Marrow Transplant and Cellular Immunotherapy, in an interview with Targeted OncologyTM.

The study enrolled patients post-HCT who received fedratinib between days +60 and +100 for up to 1 year. The trial utilized a 3+3 design to determine the maximum tolerated dose (MTD). Eleven patients were evaluable for dose-limiting toxicities (DLTs). The MTD was identified as 400 mg daily. While no DLTs occurred within the 30-day window, 4 patients withdrew due to non-DLT adverse events. Notably, only 1 patient developed severe chronic GVHD. The median progression-free survival was 12.4 months, and the 1-year overall survival was 100%.

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Exploring the interplay between myeloproliferative disorders and atherosclerosis

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Published April 3, 2025

Maham Khan, Sandipta Banerjee, Rekha Kumari, Shubhayu Roy Chowdhury, Nada Madkour, Ikponmwosa Jude Ogieuhi, Chinonyelum Emmanuel Agbo, Victor Oluwatomiwa Ajekiigbe, Olanipekun Lanny Ntukidem, Folajimi Josiah Atunde & Chukwuemelie Darlington Okeke

Abstract

The relationship between hematologic malignancies and atherosclerosis is vital in clinical conditions due to common risk factors. These two diseases may negatively affect cardiovascular health, so understanding their complex dynamics is essential for detecting disease mechanisms and establishing effective patient care. This review aims to focus on the involvement of hematologic malignancies in the onset and progression of atherosclerosis at a biological level. Furthermore, it looks at the case for heightened cardiovascular risk in patients with hematological cancers and the chances of management and treatment against it. A comprehensive literature review was performed, and studies that revealed the link between hematologic malignancies and atherosclerosis were preferred. Inclusion and exclusion criteria guided the selection of studies for consideration. The biological pathways between hematologic malignancies and atherosclerosis have been elucidated, including the inflammatory pathways and the shared risk factors. Clinical evidence reveals that cardiovascular diseases are more likely to occur in patients with hematologic cancers, thus showing the necessity of targeted preemptive measures to lower this risk. The findings reveal that it is essential to consider cardiovascular health when handling hematologic malignancies. Future research should focus on creating holistic treatment procedures that jointly deal with both conditions, which will be necessary to enhance patients’ lives and well-being.

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Navigating the peginterferon Alfa-2a shortage: practical guidance on transitioning patients to ropeginterferon alfa-2b

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Published April 3, 2025

Ruben Mesa, Abdulraheem Yacoub, Tsewang Tashi, Wanxing Chai-Ho, Chang Ho Yoon & John Mascarenhas

Dear Editor,

We write to highlight the critical shortage of peginterferon alfa-2a (peg-IFN), as confirmed by the FDA [1], which has impacted many patients with myeloproliferative neoplasms (MPNs). Those relying on peg-IFN for long-term disease control in polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) face supply disruptions that can compromise disease stability and overall health.

Ropeginterferon alfa-2b (ropeg-IFN) is a viable alternative. It is the only FDA-approved interferon for PV and is considered first-line therapy as per the January 2025 NCCN Guidelines [2]. Though not yet approved for ET or MF, off-label use may be justified in situations where no other options exist. Our group has accumulated experience in transitioning patients from peg-IFN to ropeg-IFN due to historic insurance issues and clinical trial participation, allowing us to propose practical strategies for safe conversion.

A best-practice approach to dose equivalence, based on collective experience and real-world data, is pragmatic given that no formal head-to-head dosing trials exist.[3,4,5] For patients previously on peg-IFN 135–180 µg weekly, we typically initiate ropeg-IFN at 250–350 µg every two weeks, adjusting for hematologic response and tolerability. Those on lower peg-IFN doses (45–90 µg/week) may begin on 200–250 µg every two weeks. If disease control proves challenging, starting at, e.g., 350 µg with possible escalation to 500 µg every two weeks can be considered. Whichever starting dose is chosen, close monitoring and dose adjustments are essential to maintain efficacy while minimizing toxicity.

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Global, regional, and national burden of myelodysplastic syndromes and myeloproliferative neoplasms, 1990-2021: an analysis from the global burden of disease study 2021

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Xinyue Gou 1, Zhuo Chen 2,*, Yudi Shangguan 3

Abstract

Objective

To analyze the trends and cross-country inequalities in the burden of Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) over the past 30 years and forecast potential changes through 2045.

Methods

Estimates and 95% uncertainty intervals (UIs) for incidence, deaths, and disability-adjusted life-years (DALYs) associated with MDS/MPN were obtained from the Global Burden of Diseases (GBD) 2021 database. We described the epidemiology of MDS/MPN at global, regional, and national levels, analyzed trends in the burden of MDS/MPN from 1990 to 2021 through overall, local, and multidimensional perspectives, decomposed the burden based on population size, age structure, and epidemiological changes, quantified cross-country inequalities in MDS/MPN burden using standard health equity methods recommended by the WHO, and predicted changes of MDS/MPN burden to 2045.

Results

The global incidence of MDS/MPN has shown a marked increase, escalating from 171,132 cases in 1990 to 341,017 cases in 2021. Additionally, the burden was found to be significantly greater in men compared to women. The overall global burden of MDS/MPN exhibited a consistent increase from 1990 to 2021, although the growth rate showed a noticeable slowdown between 2018 and 2021. Decomposition analysis identified population growth as a key factor influencing the variations in the burden of MDS/MPN. An inequality analysis across countries indicated that high Socio-demographic Index (SDI) countries bore a disproportionate share of the MDS/MPN burden, with significant SDI-related disparities remaining evident. Interestingly, while the incidence and deaths of MDS/MPN, along with the age-standardized rate (ASR) for DALYs, are projected to decline annually from 2020 to 2045, the absolute number of cases for these indicators is expected to continue rising. By 2045, the projected numbers are estimated to reach 457,320 cases for incidence, 82,047 cases for deaths, and 1,689,518 cases for DALYs.

Conclusions

As a major public health issue, the global burden of MDS/MPN showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. The largest share of the MDS/MPN burden was seen primarily in men, with older demographics. Countries with elevated SDI experienced a significantly higher burden of MDS/MPN. While the burden of MDS/MPN was most pronounced in high SDI quintile, the fastest growth was observed in the low-middle SDI quintile, especially in tropical Latin America. This study highlighted great challenges in the control and management of MDS/MPN, including both growing case number and distributive inequalities worldwide. These findings provide valuable insights for developing more effective public health policies and optimizing the allocation of medical resources.

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Symptom burden in myeloproliferative neoplasms: clinical correlates, dynamics, and survival impact—a study of 784 patients from the Quebec MPN research group

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April 1, 2025

Alisa Poullet, Lambert Busque, Shireen Sirhan, Robert Delage, Ghislain Cournoyer, Ines Chamakhi, Danielle Talbot, Luigina Mollica, Daniele Marceau, Vincent Ethier, Pierre Desjardins, Harold J. Olney, Michaël Harnois & Natasha Szuber

Classic BCR::ABL1-negative myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). While patients may benefit from extended survival, they also endure lifelong symptoms, ranging from mild to incapacitating [1]. These include physical manifestations related to hyperviscosity, bone pain, pruritus, constitutional symptoms, and consequences of splenomegaly, among others, as well as psychological symptoms (e.g., depression, anxiety) [2, 3]. Ultimately, symptom burden impairs quality of life (QoL) [4], an independent predictor of mortality [5]. Addressing symptom burden in MPN patients is crucial in guiding and individualizing therapy; however, several important challenges remain, including obscure mechanistic underpinnings and scarcity of robust data to inform practice. While the current patient-reported symptom assessment tool was conceived as a universal instrument for the collective MPN population—facilitating its clinical application, distinct profiles across subtypes may not be captured. Cut-off values determining ‘significant’ scores may also warrant further evaluation. Furthermore, kinetics of symptom profiles over time and correlations with biological variables have not fully been explored. The objectives of the current study were to comprehensively characterize symptom burden in a large MPN cohort, determining: i) age/sex-associated differences; ii) longitudinal dynamics and treatment effects; iii) biologic correlatives; and iv) impact on overall survival (OS) in a real-world population-based setting.

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A Patient Story: Are MPNs Hereditary?

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Our story started when I was heavily pregnant with our first child in July 2022. My husband and I were not aware that he had an MPN. One morning, before he went to the doctor before work where they told him to go to the hospital for potential internal bleeding. He went in and was admitted and spent 2 long weeks where he had numerous CT scans, endoscopies, blood test, and other various medical drips. My husband was released but we still didn’t have answers to what had caused him to have internal bleeding. We were just told they needed to do further tests; however, they were pointing towards something to do with his liver which we were very much confused by.

Time went by and we had our baby girl! We were so busy with the joy of our new arrival we had almost forgotten about the hospital. 4 weeks later we were ablet to finally see a liver specialist with our new baby and were told that he had a blood disorder that caused him to have varices in his throat that burst, causing the internal bleeding. We left the appointment with a sense of relief to finally have an answer.

A few weeks later we had an appointment with the hematologist and were told that he had a JAK2 mutation myeloproliferative neoplasm, a blood cancer. We were devastated by this news. At the age of 31, this was not something we understood or had ever heard of. The only words we heard were “blood cancer” and, even though his hematologist is very knowledgeable and reassuring, we left feeling like our world had been turned upside with a 6-week-old baby girl.

After being told that his MPN diagnosis was not hereditary, we spent numerous hours researching the condition to better understand what we were dealing with. We moved on, so to say, and made the most of every day.

Just before our daughter turned one, we took her into the doctor’s office because she had a cough, and I was worried that she might have enlarged lymph nodes. The doctor didn’t seem too concerned but referred her for some blood tests just to be on the safe side considering my husband’s recent diagnosis. Her test results showed high platelets, and we were told to have the tests repeated as the rise in platelets could have been due to iron deficiency or an infection.

The second blood test once again showed that her platelets were unusually high. The hematologist referred us to genetic testing and another full blood count. Her results came back stating she also had a JAK2 mutation, the same one as my husband’s (JAK2 V617I). After this diagnosis, we sent off nail clipping to confirm that he has a germline mutation.

When our daughter was 6 months old, we became pregnant with our second child. We learned that my mother-in-law also has the JAK2 mutation but hers was never activated. My husband has now been officially diagnosed with polycythemia vera (PV) and is being checked every 6 months with stable blood work. We are now focused on living a positive, happy life despite all the challenges we were presented and remain grateful for our family every day.

 

Distress May Be Under-Recognized in Patients With MPN

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March 28, 2025

John Schieszer

Distress is a critical yet underrecognized factor affecting quality of life, treatment adherence, and healthcare utilization in classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF), according to results of a retrospective study. The study revealed that despite consensus recommendations, most patients with distress ≥4 were not evaluated by supportive services (SS).

“Our findings underscore the importance of integrating distress screening with actionable follow-ups to ensure that patients receive timely supportive care,” said first study author Rushil V. Patel, MD, an assistant professor of Hematology/Oncology at The University of Alabama at Birmingham. “For hematologists, the key takeaway is that screening alone is insufficient and systematic referral pathways and proactive engagement with supportive services are essential. An interdisciplinary approach could significantly enhance patient-centered care.”

There is an urgent need to address the unmet needs of this population. The National Comprehensive Cancer Network (NCCN) recommends screening patients for distress by a self-reported scale (0-10) and to refer those with scores ≥4 to SS.

Researchers looked at 141 patients (44 PV, 49 ET, and 48 MF). The median age was 63 years (range, 25-89). The researchers retrospectively identified MPN patients at a single center to measure the proportions of patients with distress ≥4 evaluated by an SS (chaplaincy, integrative oncology, palliative medicine, psychiatry, psychology, and social work).

The team also investigated acute care utilization (ACU; ≥1 ED visit or hospitalization) within 6 months of electronic distress screening (EDS). In order to stratify variables associated with distress, the investigators obtained sociodemographic, disease characteristics, and symptom score data. The cohort was predominantly female (62%) and White (77%).

As part of routine care, the NCCN recommends using the MPN-Symptom Assessment Form Total Symptom Score (SAF TSS), which is a validated measure of 10 symptoms clinically relevant to MPNs. Data captured from the EDS included location, time of screening and patient-reported information (gender, race, ethnicity, psychosocial variables). These were linked to the electronic medical record (EMR). Distress was based on a single self-reported question: “How much distress have you been feeling in the past week?”

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