Diagnosis and Management of PV and ET in Pediatric Populations Needs Improvement

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Caleb Rans, PharmD
Publish Date

Polycythemia vera (PV) and essential thrombocythemia (ET) are rarely diagnosed in children, adolescents, and young adults. As the median age at diagnosis for these conditions is usually over 60 years, few pediatricians are familiar with their clinical, biological, and genetic features.1-3 Early diagnosis is essential to assess the need for specialized treatments and to prevent long-term complications, such as hemorrhage, thrombosis, or progression to secondary malignancies.1

In a 2-part study published in the European Journal of Pediatrics, Agathe Picard, MD, of the department of pediatric oncohematology at the Rennes University Hospital in France, and colleagues, analyzed practices around the diagnosis and management of pediatric patients with PV and ET in France.

Methodology and Study Design

In the first part of the study, a national practice survey about pediatric patients diagnosed with PV or ET was performed. The 8-question survey was sent to all pediatrician members of the leukemia committee of Société Française de lutte contre les Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), and all hematologist members of France Intergroupe des Syndromes Myéloprolifératifs (FIM).

AYA [patients] should be referred to specialized units that consider the social, psychological, and educational needs of these patients.

In the second part, a retrospective cohort study was conducted at 7 pediatric oncohematology departments in western France. The researchers analyzed clinical, biological, and genetic data, as well as treatment and complication patterns from 17 pediatric patients with PV or ET, all of whom were diagnosed before the age of 18.

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Assessing Risk for JAK Inhibitor Selection in Myelofibrosis

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By Targeted Oncology Staff

In part 1, experts explores how assessing individual risk factors is crucial in selecting the appropriate JAK inhibitor for patients with myelofibrosis.

CASE

AARON T. GERDS, MD, MS: How do you use molecular testing, bone marrow results, and clinical features to stratify risk in patients with myelofibrosis?

PRITHVIRAJ BOSE, MD: At this point, I believe we are all receiving the myeloid mutation panels. We also order JAK2, MPL, and CALR: the 3 drivers. However, most clinicians would order a myeloid mutation panel because we know that many of the mutations are prognostic. This is the whole point of risk stratification, which is now increasingly sophisticated and integrates multiple clinical, molecular, [and] cytogenetic variables to determine who needs a transplant.

These are the first actions I take when speaking with a new patient. I get an idea of their risk in terms of survival and prognosis, and that informs my decision to refer them to transplant. I then counsel the patient appropriately.

I do not believe molecular testing informs treatment because our drugs are, for the most part, mutation agnostic. All we have are JAK inhibitors, which are not mutation specific. However, from a prognostic standpoint, the [role] of molecular testing is key.

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Working to Address Unmet Medical Needs in MPNs

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April 24, 2025

Author(s): John Crispino

Fact checked by: Alex Biese, Spencer Feldman

In his research into myeloproliferative neoplasms, or MPNs, John Crispino is focused on a couple of key areas when it comes to understanding the underlying biology of the disease, as he explained in an interview with CURE.

Crispino is the director of the division of experimental hematology at St. Jude Children’s Research Hospital in Memphis, Tennessee, where he is also the Wall Street Committee Endowed Chair and principal investigator of the Crispino Lab. The Crispino Lab, according to its website, is focused primarily on myeloid cells, centered on the mechanisms of normal and abnormal cell development.

“There are two major areas that we study,” Crispino told CURE. “The first is the biology of megakaryocytes. Those are the cells that make platelets. … The second major area of research is on leukemic progression. So I would say that that progression to acute leukemia is really terrible outcome for patients, and we have very few therapies for patients that do advance at that stage. So our research in the past few years has focused on understanding the mechanism.”

Crispino sat down recently with CURE to discuss his research.

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Protein Disulfide Isomerase Could Be Therapeutic Target for MF

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Özge Özkaya, MSc, PhD
Publish Date

Protein disulfide isomerase may be involved in the underlying pathogenesis of thrombotic events in Philadelphia-negative myeloproliferative neoplasms such as myelofibrosis (MF), according to a new study published in the Egyptian Journal of Internal Medicine.

It could also be valuable in predicting the risk of developing thromboembolic events, the researchers noted.

These findings suggest that protein disulfide isomerase could be used as a therapeutic target to prevent thrombotic events in patients with MF and other myeloproliferative neoplasms.

For the study, a team of researchers, led by Mai Galal Elshenoufy, MD, PhD, from Cairo University in Egypt, measured the levels of protein disulfide isomerase in the serum of patients with myeloproliferative neoplasms and assessed its role as a possible marker of increased risk of thromboembolic events.

They found that the levels of the enzyme were pathologically high in the serum of patients with myeloproliferative neoplasms compared to controls. The levels were also higher in patients with arterial thrombosis, but this finding had no statistical significance.

Future work should evaluate the levels of protein disulfide isomerase in a larger group of patients with myeloproliferative neoplasm with and without thrombotic events, and in patients with arterial versus venous thrombosis, they said.

Finally, measuring the levels of protein disulfide isomerase before and after aspirin therapy could give clues about the effect of this treatment, they added.

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Clinical Trials Can Open Doors for Patients With Myeloproliferative Neoplasms

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By Kathryn Johnson, DNP, MSc, FNP-BC
Fact checked by Bridget Hoyt

Educating patients on the “risks and benefits” of clinical trials is a part of the pipeline for better treatment options in myeloproliferative neoplasms (MPNs) in which nurses can engage, said a nurse practitioner.

For patients with MPNs, clinical trials have paved the way for better treatment outcomes, increasing options vastly within a short amount of time. In an interview with Oncology Nursing News, Kathryn Johnson, DNP, MSc, FNP-BC, spoke to the importance of the development of these options and nurses’ role in making those possible.

As Johnson, a clinical program manager at Icahn School of Medicine at Mount Sinai New York, outlined, nurses can play a key part in informing patients on what to expect on clinical trials. She advised not only being prepared with information patients should know, but making time for patients to air their concerns and ask questions as well.

Johnson added that in the time that she has been working in oncology, multiple advancements have been made in the treatment of MPNs. She expects this trend to continue in the coming years.

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Dr Harrison on Factors Influencing Patient Prognosis and Treatment Selection in Myelofibrosis

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April, 22, 2025

Author(s): Claire Harrison, MD, FRCP, FRCPath

Fact checked by: Ashling Wahner ,Courtney Flaherty

Claire Harrison, MD, FRCP, FRCPath, a professor of myeloproliferative neoplasms, a consultant, and a clinical director at Guy’s and St. Thomas’ Hospital, discussed the general treatment algorithm for myelofibrosis management, as well as how certain mutations affect patient prognosis and treatment decision-making.

Myelofibrosis is a heterogeneous myeloproliferative neoplasm with significant variability in clinical presentation and disease trajectory, Harrison began. Accurate diagnosis is the foundational step, necessitating careful review of histopathology, peripheral blood findings, bone marrow morphology, and molecular genetics—even in patients who have been referred from other institutions, she stated. Key diagnostic indicators include the presence of splenomegaly and constitutional symptoms, as well as driver mutations, such as JAK2, CALR, and MPL, which support a diagnosis of myeloproliferative neoplasm, Harrison detailed.

Furthermore, assessment of patient-specific factors is essential to inform therapeutic strategy, she continued. This includes evaluating comorbid conditions that may limit treatment options and determining the dominant clinical manifestations of each patient’s disease, Harrison noted. Patient education plays a critical role in this step, with efforts made by oncologists to ensure patient comprehension of the diagnosis—often explicitly referring to myelofibrosis as a “blood cancer”—and to connect patients with advocacy resources when appropriate, she explained.

Prognostication in myelofibrosis incorporates multiple validated models, with modern tools integrating both clinical and molecular data, Harrison said. Driver mutations aid diagnostic classification; however, the absence of these mutations in triple-negative cases warrants expanded next-generation sequencing to identify alternative pathogenic mutations, according to Harrison. The presence of high molecular risk mutations—including ASXL1, IDH1/2, SRSF2, U2AF1, TP53, RUNX1, and NRAS—portends a poorer prognosis and should influence risk stratification and treatment planning, Harrison concluded.

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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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Real world outcomes of momelotinib in myelofibrosis patients with anemia: results from the MOMGEMFIN study

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Lucía Pérez-Lamas, Adrián Segura Diaz, Regina García Delgado, Alberto Álvarez-Larrán, María Alicia Senin, Elvira Mora, María Laura Fox, Irene Pastor Galan, Gemma Azaceta, et al.

Standard treatment for symptomatic myelofibrosis (MF) patients includes JAK inhibitors (JAKi) like ruxolitinib and fedratinib [1,2,3,4], but their effectiveness is often limited by transient responses and the development of cytopenias [5]. Recently, momelotinib received FDA and EMA approval for treating splenomegaly and disease-related symptoms in adult patients with MF and anemia. In addition to JAK1/JAK2 inhibition, momelotinib targets the activin A receptor type 1 (ACVR1), which regulates iron metabolism through hepcidin, contributing to its unique therapeutic profile [6]. The efficacy of momelotinib in improving symptoms, reducing spleen size, increasing hemoglobin (Hb) levels, and reducing transfusion dependency in both JAKi naïve and JAKi exposed MF patients has been demonstrated in several clinical trials [7,8,9,10,11].

Given its recent approval, real-world data on momelotinib use is still limited. To gather evidence on its efficacy and safety in routine practice, the Spanish Group of Philadelphia-negative Myeloproliferative Neoplasms (GEMFIN) initiated the MOMGEMFIN study, analyzing MF patients treated with momelotinib through a managed access program.

This study was a multicenter, retrospective analysis of adult patients treated with momelotinib (JAK-naïve or JAK-exposed) from March 2023 to July 2024. Eligible participants had primary or secondary MF with anemia and disease-related symptoms or symptomatic splenomegaly. Anemia was defined as Hb values less than 11 g/dL for men and less than 10 g/dL for women. Anemia response was based on the 2024 IWG-ELN criteria [12]. Transfusion dependency was classified as requiring at least one red blood cell (RBC) unit per month or three or more units over 12 weeks. Spleen evaluation followed the 2013 ELN (IWG-MRT) criteria [13]. Adverse events (AEs) were graded per CTCAE version 5.0.

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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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