Primary myelofibrosis with increased haemoglobin concentration at presentation

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Primary myelofibrosis (PMF) is a myeloproliferative neoplasm.
• Disease characteristics at diagnosis influence prognosis and treatment strategies.
• The role of elevated hemoglobin concentration in PMF remains incompletely understood.

Purpose of the Study:

• To investigate the clinical characteristics and outcomes of PMF patients with elevated hemoglobin at diagnosis.
• To identify factors associated with survival in this specific PMF subgroup.
• To understand the implications of high hemoglobin for disease progression and inflammation.

Main Methods:

• Retrospective analysis of 963 PMF patients from the Pavia-CSM database.
• Comparison of clinical and molecular features between patients with and without elevated hemoglobin at diagnosis (females ≥160 g/L, males ≥165 g/L).
• Assessment of disease activity markers, inflammation, progression, and survival.

Main Results:

• 100 patients (10.4%) had elevated hemoglobin at diagnosis, predominantly female and younger.
• These patients exhibited higher white blood cell (WBC) and platelet counts, and higher JAK2 V617F variant allele frequency (VAF).
• They presented with less active disease (smaller spleen, lower LDH, lower CD34+ cells, less fibrosis), reduced inflammation (lower hs-CRP), slower progression to myelodysplasia, and longer survival (22 vs. 15 years).
• In this subgroup, age >50 and JAK2 V617F VAF >75% correlated with worse survival.

Conclusions:

• PMF with elevated hemoglobin at diagnosis represents a distinct subtype characterized by JAK2 V617F-driven hyperproliferation with reduced inflammation.
• This unique phenotype is associated with a less aggressive disease course and improved survival.
• These findings have significant implications for risk stratification and therapeutic approaches in PMF.