Myeloproliferative Neoplasm

Persistent unexplained thrombocytosis with prior arterial thrombosis should raise suspicion for an occult myeloproliferative neoplasm, whereas postoperative HIT remains a clinical consideration despite negative functional assays, particularly in the context of potent P2Y12 receptor inhibition.

Thrombotic and hemorrhagic complications represent the most common cause of morbidity in MPNs, however the mechanisms underlying this pathology remain opaque. Cytoreduction and antithrombotic therapies, the mainstay for treatment of MPNs, inadequately address platelet dysfunction, though emerging therapies targeting the MPN clone are promising. Thus, a deeper understanding of megakaryocyte and platelet biology in MPNs is essential for the development of precise therapeutic strategies to reduce thrombotic complications and improve patient outcomes.

Ropeginterferon alfa-2b-njft (ropeg), a mono-PEGylated interferon-α, showed efficacy and safety in patients with hydroxyurea-intolerant/resistant essential thrombocythemia (ET) in the phase 3 SURPASS-ET largely conducted in Asia. Ropeg showed efficacy and substantial molecular responses with good overall tolerability across a broad ET population. PharmaEssentia.

In the latter, the observed CV risk might stem from failure of JAKi to fully inhibit prothrombotic pathways induced by cytokines (TNF and IL-17) and the potential dose-related vascular toxicity. Understanding these binary effects will provide new insights into the divergent CV impact of JAKi.

Although limited by its retrospective character, small sample size and incomplete molecular data, this study shows that long-term survival after allo-HCT is achievable in patients with MDS/MPN with Neutrophilia, particularly in younger individuals with low disease burden. However, relapse and NRM remain major challenges underscoring the need for optimized post-transplant strategies.

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | Trial completion date: Aug 2029 --> Jun 2026 | Trial primary completion date: Aug 2027 --> Jun 2026

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

P=N/A, N=500, Not yet recruiting, Weizmann Institute of Science

At present, however, this evidence base is constrained by small and heterogeneous cohorts, limited cross-platform reproducibility, and a scarcity of independent external validation for candidate protein panels. Realising this vision will require multicentre standardisation, analytically validated panel assays, and prospective clinical studies that translate molecular findings into decision-grade tools for patients with MPNs.

P=N/A, N=50, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders.

CML and PV exhibited distinct cytokine-driven transcriptional signatures, whereas ET and PMF exhibited minimal alterations. These findings support the clinical utility of NanoString technology for bone marrow specimens and highlight disease-specific immune pathways as potential diagnostic biomarkers in MPNs.