Publication Only: Myeloproliferative neoplasms - Clinical
Myelofibrosis (MF) is a classical myeloproliferative neoplasm characterized both in its primary and secondary form by splenomegaly, constitutional and disease-related symptoms as well as by cytopenias. Aberrant constitutive activation of the JAK-STAT pathway is core to its pathogenesis and the inhibitors of this pathway such as ruxolitinib, approved for MF treatment seven years ago, have been proven effective in a majority of patients.
To describe ruxolitinib response and median survival in a group of patients diagnosed with MF in a single center and correlate it with the molecular profile, hematimetric data and previous myeloproliferative neoplasm (polycythemia vera (PV) or essential thrombocytosis (ET)).
Of a total of one-hundred twenty four patients diagnosed with MF in our center, thirty eight patients were treated with ruxolitinib between April 2012 and September 2018. Diagnosis of myelofibrosis was made based on bone marrow examination and according to the updated WHO criteria. Molecular study was carried out in peripheral blood for the mutation JAK2V617F as well as allele-specific PCR for mutations type 1 and type 2 of exon 9 of calreticulin (CALR) gene, and exon 10 of myeloproliferative leukemia virus (MPL) gene. The prognostic risk stratification was carried out according to the International Prognostic Index (IPSS). All patients treated with ruxolitinib belonged to the intermediate group-2 or were classified as high risk. Statistical analyses were performed in SPSS 15.0.
Average age of the group was 63 years (range 36-88). 58% were males and 42% female. Average leukocyte, haemoglobin and platelet counts at diagnosis were 9,8x10e9/l (1.9-62), 10.3 g/dl (6-15.7) and 236x10e9/L (52-789), respectively. 47% of patients had a previous diagnosis of another MPN (50% PV and 50% ET). JAK2V617F mutation was present in 70.3%, and CARL and MPL mutation in 12.5% and 2.6%, respectively. All patients responded to ruxolitinib although 39% finally lost this response, with a 13% evolution to acute leukemia, 40% of this group being subjected to allogeneic SCT. Currently, 73% of patients are alive. Six-year overall survival of patients with JAK2V617F mutation was 80% compared to 60% of those with wild-type mutational status, statistical significance not being reached. Patients with previous MPN also had greater six-year overall survival (70%) than those with idiopathic MF (56%).
Patients with MF with JAK2V617F mutation and previous MPN present a greater duration of response to ruxolitinib than others, probably due to greater inhibition of the preponderant pathogenetic mechanism and the more effective action of the drug on a more differentiated progenitor than in idiopathic MF, although broader studies are required to confirm these results.