Guidelines Needed for Managing MPNs in AYA Patients, Review Says

The management of myeloproliferative neoplasms (MPNs) in adolescent and young adult (AYA) patients is currently similar to that of older patients. However, comprehensive research is needed to form guidelines for this younger population.

Although myeloproliferative neoplasms (MPNs) are most commonly diagnosed in elderly adults, advancements in blood surveillance have facilitated their diagnosis in a growing number of adolescent and young adults (AYAs). A review published in Best Practice & Research Clinical Haematology aimed to characterize MPNs in the AYA population vs the general population of individuals with MPNs.

MPNs are rare clonal stem cell disorders, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), that lead to myeloid hyperplasia. These classical MPNs increase an individual’s risk of thromboembolic events and can potentially transform into acute myeloid leukemia (AML).

Although MPNs are most commonly diagnosed in individuals in their 70s, they are increasingly found in younger patients who tend to display different clinical and molecular traits than older patients. The present review aimed to provide further understanding of disease characteristics and management strategies for MPNs in AYAs, defined as patients aged 15 to 39 years.

AYAs are thought to account for 10% to 20% of patients with MPNs, with ET being the most common type of MPN in this cohort. Like older adults with MPNs, AYAs with MPNs showed a higher risk of thromboembolic events compared with the broader AYA population. Splanchnic vein thrombosis (SVT) is markedly more prevalent in AYAs with MPNs vs older adults. More than 75% of the venous events reported in AYAs are SVT, whereas it only accounts for 7.5% of venous events in older patients.

Up to 50% of AYA patients are asymptomatic, and headache is the most common symptom among them. Pruritus was seen in 20% of AYAs and 40% of older adults, and erythromelalgia was seen in less than 5% of AYAs, similar to older adults. Splenomegaly was observed at higher rates in AYAs with ET or PV compared with older adults. It was present in 28% of AYAs with ET and 57% of those with PV vs 25% in older patients with PV and 14% of those with ET. The rate of transformation to AML was similar in AYAs compared with older adults, but time to transformation was longer (19-20 vs 7-8 years).

The main goals of MPN management are reduction of thromboembolic event risk and managing symptoms, and MPN management is generally the same in AYAs and older populations. However, there are not yet any validated risk stratification scores for AYAs due to a lack of data on MPNs in this cohort. Instead, guidance for older adults is also applied to AYAs, and individualized risk assessments are crucial to effective disease management. For example, factors such as ideal hematocrit level targets have yet to be determined for the AYA population. Pregnancy is a concern in AYA patients due to an increased with ofthrombosis, hemorrhaging, and placental dysfunction, and interdisciplinary coordination is crucial to minimize risks for pregnant individuals.

For intermediate and high-risk patients who have ET or PV, interferon (IFN) is the recommended cytoreductive agent in AYA patients, but the rate of uptake is only estimated at up to 23%. Hydroxycarbamide (HC), in contrast, is used in 52% of cases where cytoreduction is recommended. The review authors note that IFN has a significant adverse effect profile that may steer physicians away from it in this population. Therefore, they recommend pegylated IFN (Peg IFN), which is typically better tolerated.

“In our practice, unless contraindicated, we propose peg IFN for all AYA patients, commencing at the lowest dose of 45 mcg/week subcutaneously and increasing according to response and tolerability,” the authors wrote. For patients who are intolerant to HC and peg IFN, anagrelide is another option but warrants monitoring for bone marrow fibrosis.

PMF treatment is centered on symptom burden management, but AYAs are generally considered low risk because age is central factor in risk stratification. The only curative treatment for high-risk patients is allogenic stem cell transplantation, meaning early diagnosis is crucial.

Overall, the management of MPNs in AYA patients is similar to that of older patients. However, more comprehensive research is needed to form guidelines for the younger population.

“Although the last decade has seen growing interest in AYA MPNs, there remains an unmet need to establish an international global prospective cohort of AYA patients, with long follow-up, in order to uncover complications and long-term outcomes,” the authors concluded. “Greater understanding of the pathogenesis in the AYA and developing age-specific risk stratification is required to aid in identifying patients at high risk of thrombosis and transformation events in addition to guiding therapies.”


Amerikanou R, Lambert J, Alimam S. Myeloproliferative neoplasms in adolescents and young adults. Best Pract Res Clin Haematol. Published August 14, 2022. doi:10.1016/j.beha.2022.101374