Easily Applicable Predictive Score for Differential Diagnosis of Prefibrotic Primary Myelofibrosis from Essential Thrombocythemia

SIMPLE SUMMARY: Essential thrombocythemia and primary myelofibrosis are Philadelphia-chromosome negative myeloproliferative neoplasms with a similar initial phenotypic presentation with thrombocytosis but totally different prognoses and treatment approaches. Patients with primary myelofibrosis compared to essential thrombocythemia had significantly shorter survival as well as higher rates of progression to overt myelofibrosis and leukemic transformation. Around 20% of patients with an early prefibrotic phase of primary myelofibrosis have poor outcomes with a median overall survival of less than 3 years. The aim of our study was to determine significant clinical and laboratory parameters at presentation to differentiate these two entities, according to which we have developed and validated a predictive diagnostic prePMF score. Based on this score, patients with ≥2 points are suspected to have primary myelofibrosis, and hematological work-up should be performed as soon as possible because there is a chance that some of these patients may have rapid disease progression and a shortened life expectancy. ABSTRACT: Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments.