The Clinical Phenotype of Patients with Primary Myelofibrosis, Polycythemia Vera, and Essential Thrombocytosis Whom Only Manifest WHO Grade 1 Fibrosis

Introduction:

The clinical phenotype of patients with myeloproliferative neoplasms (MPNs) including primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET) who manifest WHO grade 1 (on a 0-3 scale) for intramedullary fibrosis is poorly defined, and may represent MPN patients in a transitional state. We have specifically observed patients with existing PV and ET who manifest clinical progression towards a post PV/ET phenotype (IWG-MRT criteria) yet fail to progress to a 2+ marrow fibrosis. In contrast, the 2008 WHO definition of PMF does not require a minimum fibrosis threshold as long as patients meet the diagnostic criteria. In this study, we retrospectively analyzed the clinical characteristics and outcomes of MPN patients with 1+ marrow fibrosis.

Methods:

MPN patients with WHO grade 1 (scale 0-3) fibrosis within two institutional databases were identified. The clinical characteristics, laboratory, and outcome data were collected. Data were compared between PMF and PV/ET patients. 2008 IWG-MRT criteria were applied to PV/ET patients with exclusion of fibrosis component.

Results:

91 MPN patients with WHO grade 1 fibrosis were identified, PMF in 33 patients (36%), PV in 37 (41%), ET in 20 (22%), and MPN-U in 1 (1%). The population characteristics are reported in Table 1. The majority (56%) of patients exhibited one or more symptoms (weight loss, night sweats, early satiety, bone pain, fatigue). The presence of symptomatic disease was similar between groups, with 52% PMF versus 57% PV/ET exhibiting at least one symptom. Symptoms were more severe in the PMF group with DIPSS risk of intermediate 2 or higher being present in 39%(PMF) versus 29% (PV/ET). Erythrocyte transfusion dependence occurred in a small percentage of overall population (9%), and was seen primarily in the PMF group (6/8 patients). Incidence and severity of splenomegaly was higher in the PMF group, with 55% having splenomegaly versus 43% of the PV/ET group. A higher incidence of a leukoerythoblastic blood smears was seen in PMF (45%) than PV/ET (38%). Two or more prior medical therapies were utilized in 45/90 (49%) of patients, with the most common prior therapies including hydroxyurea (71%), pegylated interferon (28%), anagrelide (18%), Jak inhibitor (13%), lenalidomide (4%), and prednisone (4%). At the time of this analysis, 78/91 patients (86%) were alive. When IWG-MRT criteria were applied to the PV/ET group, 38/58 (66%) of patients fulfilled criteria for diagnosis of post-PV/ET myelofibrosis (except for the 2+fibrosis requirement).

Discussion and Conclusion:

PV and ET patients with WHO grade 1 marrow fibrosis manifest a phenotype that suggests progression to post-PV/ET myelofibrosis, and clinically overlap with PMF phenotype; however, these patients currently fail to meet 2008 IWG-MRT diagnostic criteria for this diagnosis on basis of sub-threshold fibrosis. MPN progression represents a biological spectrum and definitions of progression in ET/PV may benefit from other criteria not restricted by degree of fibrosis.