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

Abstract

Primary myelofibrosis (PMF) is hallmarked by stromal bone marrow changes, whose accurate evaluation holds diagnostic and prognostic implications. The reticulin fibrosis (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 PMF (oPMF). Overall, stromal changes evolved harmonically in the 2 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, particularly in oPMF. Receiver operator characteristic analysis confirmed 5 as the most accurate RCO-S cutoff 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 overall survival, and higher cumulative incidence of leukemic transformation. Notably, integrating RCO-S into the mutation-enhanced international prognostic score system prognostic model improved risk stratification and accuracy compared with 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.

Keywords: bone marrow microenvironment; collagen deposition; osteosclerosis; primary myelofibrosis; prognosis; reticulin fibrosis.