Clinical and Prognostic Correlates of the Reticulin-Collagen-Osteosclerosis (RCO) Score in Primary Myelofibrosis

Primary myelofibrosis (PMF) is hallmarked by stromal bone marrow changes, whose accurate evaluation holds diagnostic and prognostic implications. The reticulin (MF), collagen (Co), osteosclerosis (Ost) score (RCO-S) was developed in 2017 and proved to be accurate and prognostically informative. In this retrospective, single-center study, we validated the RCO-S and explored its clinical, genetic and prognostic correlates in a large cohort of patients with PMF, including 121 prefibrotic (pre-PMF) and 101 overt (oPMF) PMF. Overall, stromal changes evolved harmonically in the two PMF subtypes, with pre-PMF showing milder alterations. A higher RCO-S was associated with distinct high risk clinical and molecular features and shortened overall survival (OS), particularly in overt PMF. ROC analysis confirmed 5 as the most accurate RCO-S cut-off value (RCO-S5) to differentiate low-grade (<5) and high-grade (>5) PMF. High-grade disease was associated with adverse clinical and molecular profiles, worse OS, and higher cumulative incidence of leukemic transformation. Notably, integrating RCO-S into the MIPSS70 prognostic model improved risk stratification and accuracy compared to the standard scoring system. Despite study limitations, our findings showed that 1) the RCO-S provides a comprehensive assessment of PMF stromal changes; 2) it holds clinical, genetic, and prognostic relevance; and 3) its integration into existing prognostic models has the potential to improve prognostic stratification.