How I manage myeloproliferative neoplasm‐unclassifiable: Practical approaches for 2022 and beyond

Abstract

Myeloproliferative neoplasm (MPN)‐unclassifiable (MPN‐U) or not otherwise specified represents a rare, poorly defined and heterogeneous group of MPNs. Disease incidence is difficult to define but likely represents close to 5% of all MPNs when strict World Health Organisation (WHO) criteria are applied. Dynamic review over time is required to assess if the disease can be re‐classified into another MPN entity. A diagnosis of MPN‐U leads to many challenges for both the patient and physician alike including lack of agreed monitoring and therapeutic guidelines, validated prognostic markers and licenced therapies coupled with exclusion from clinical trials. MPN‐U has an inherent risk of an aggressive clinical course and transformation in some but who, and when to treat in the chronic phase, including identifying who may require more aggressive therapy at an earlier stage, remains elusive. Moreover, despite the significant thrombotic risk, there is no agreement on systematic primary thromboprophylaxis. We hereby provide a contemporary overview of MPN‐U in addition to four illustrative cases providing our collective suggested approaches to clinical challenges.

The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms

“…However, the latter might also be seen in patients with clonal hematopoiesis of indeterminate potential (CHIP), which should be kept in mind during interpretation of such mutations, especially in elderly patients. Interestingly, in comparison with previous published series, 117 a great majority of MPN‐U cases diagnosed according to the 2016/17 WHO criteria 1,2 appear to represent very early stage MPN [i. e., displaying no (MF‐0) or mild (MF‐1) reticulin fibrosis] 119,120 This observation suggests that the widespread application of molecular screening tests in conjunction with the current diagnostic criteria allows at least a confirmation of the presence of true MPN and validates MPN‐U as an entity associated with a considerable rate of thrombosis and risk of inherent transformation to a given specific subtype in the majority of the cases. The spectrum of clinical phenotype, treatments applied, and natural history of patients with MPN‐U might be similar to those with otherwise ICC‐defined MPN 119 …”

“…However, most studies show an incidence of 10%–15% or even less 117 . Provided diagnostic criteria (Table 6) are strictly applied, its real incidence is reduced to about 5% 118–120 . and disease descriptions; in a recent national MPN registry, 82 (5.4%) out of 1512 MPN listings were reported to have met the 2016/17 WHO diagnostic criteria for MPN‐U 119 …”

“…117 Provided diagnostic criteria (Table 6) are strictly applied, its real incidence is reduced to about 5%. [118][119][120] In cases presenting with myelodysplastic features effects of any previous cytoreductive treatment, severe comorbidity, and changes during the natural progression of the disease process must be carefully excluded.…”

Cerebral venous sinus thrombosis with head trauma and unclassifiable myeloproliferative neoplasm: a case report

“…The CVST patients with ineffective anticoagulation or concomitant cerebral hemorrhage can choose intravascular intervention treatment, which included venous sinus contact thrombolysis, mechanical thrombectomy, balloon catheter thrombectomy, and venous sinus stent angioplasty (1,2,4). Clinically stable MPN-U does not require treatment yet, but follow-up and observation are needed (13). In our case, the symptoms were improved after subcutaneous injection of low molecular weight heparin.…”

Advances in Molecular Understanding of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis: Towards Precision Medicine

“…Unlike other well-defined MPNs, MPN-NOS lacks standardized treatment guidelines and the utility of mutational and cytogenetic analysis as a prognostic tool in MPN-NOS/MPN-U is not well established. This limitation is due to the small number of studies, which requires further validation [95]. Treatment strategies, typically adapted from other myeloproliferative disorders, focus on symptom management and disease monitoring, often involving hydroxyurea for cytoreduction and low-dose aspirin for thromboprophylaxis based on individual risk.…”