High molecular risk variants, severe thrombocytopenia and large unstained cells count affect the outcome in primary
Zuzanna Kanduła1, Michał Janowski2, Barbara Więckowska3
1Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznan, Poland. zuzannakandula@gmail.com.
Abstract:
Apart from the driver mutations, high molecular risk (HMR) variants and other factors have been reported to influence the prognosis of primary myelofibrosis (PMF). The aim of our study was to investigate the impact of laboratory and molecular characteristics at the time of diagnosis (TOD) on the PMF outcome. The study group consisted of 82 patients recruited from three Polish university centers. Among the driver mutations, only CALR type 1 positively influenced the overall survival (OS). The risk of progression to accelerated or blastic disease phase (AP/BP) did not depend on the driver mutation type, but was closely associated with the presence of HMR variants (p = 0.0062). The risk of death (ROD) was higher in patients with HMR variants (OR[95%CI] = 4.33[1.52;12.34], p = 0.0044) and in patients with a platelet count at the TOD between 50-100 G/L (HR[95%CI] = 2.66[1.11;6.35]) and < 50 G/L (HR[95%CI] = 8.44[2.50;28.44]). Median survival time was 7.8, 2.2 and 1.4 years in patients with large unstained cells (LUC) count of [0.0-0.2], (0.2-0.4] and > 0.4 G/L at the TOD, respectively. We found an unexpected, hitherto undescribed, association between LUC count at the TOD and PMF prognosis. Our analysis led to the following conclusions: in PMF patients at the TOD 1) the presence of HMR variants, especially combined, is associated with an increased risk of progression to the AP and BP, and shorter OS, 2) severe thrombocytopenia confers worse prognosis than the moderate one, 3) LUC count is closely related with the disease phase, and associated with the ROD and OS.
Insights
High molecular risk (HMR) variants and large unstained cells (LUC) at diagnosis significantly impact primary myelofibrosis (PMF) prognosis. HMR variants increase progression risk, while LUC counts correlate with overall survival and disease phase.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Primary myelofibrosis (PMF) prognosis is influenced by factors beyond driver mutations.
- High molecular risk (HMR) variants and other laboratory characteristics may impact patient outcomes.
Purpose of the Study:
- To investigate the prognostic impact of laboratory and molecular characteristics at the time of diagnosis (TOD) in primary myelofibrosis (PMF).
- To identify key factors influencing overall survival (OS) and progression to accelerated or blastic disease phases (AP/BP).
Main Methods:
- Retrospective analysis of 82 PMF patients from three Polish university centers.
- Evaluation of driver mutations, HMR variants, platelet counts, and large unstained cells (LUC) at diagnosis.
- Statistical analysis to determine associations with OS, risk of progression (ROD), and disease phase.
Main Results:
- CALR type 1 driver mutation was associated with improved OS.
- HMR variants significantly increased the risk of progression to AP/BP and the risk of death (ROD).
- Low platelet counts (<100 G/L) at TOD were linked to worse prognosis; LUC count showed a strong correlation with disease phase, ROD, and OS.
Conclusions:
- HMR variants at diagnosis are critical indicators of poor prognosis in PMF, associated with increased progression and reduced OS.
- Severe thrombocytopenia and elevated LUC counts at diagnosis are significant adverse prognostic factors in PMF.
- LUC count represents a novel, important prognostic marker in PMF, correlating with disease severity and survival outcomes.
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