Abstract Topic: 16. Myeloproliferative neoplasms - Clinical
Background: Myelofibrosis (MF) is a clonal hematological malignancy which originates al the level of the pluripotent hematopoietic stem cell being the mediators of stimulation of fibroblast proliferation derived from megakaryocytes and monocytes. MF can present de novo as primary myelofibrosis (PMF) or can be secondary to an antecedent polycythemia vera (PV) or essential thrombocytosis (ET). Recognition of the driver mutations JAK2 V617F, CALR, and MPL has led to the development of ruxolitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2 that has transformed therapy for myelofibrosis.
Aims: From a clinical database of 149 patients, we studied the differences between those with PMF and secondary myelofibrosis (SMF) regarding epidemiological data, molecular status, ruxolitinib response and survival.
Methods: Diagnosis of primary MF (PMF) an post-Essential Thrombocytemia/post-Polycithemic MF was made according to the WHO 2016. Molecular tests for detection for JAK2, MPL and CALR mutations were performed. Ruxolitinib starting dose was decided accordingly to prescribing information.Survival analysis was performed by means of Kaplan-Meier curves and differences between KM curves were evaluated using the Log-rank test. P values less than 0.05 were considered satistically significant. Analyses were performed with SPSS software v.15.
Results: Median age was 64 years (range 36–88); median haemoglobin was 110 g/l (range, 60–157) and 48,1% patients had a transfusion-dependent anemia. Median platelet an leucocyte counts were respectively 311 × 109/l (range, 52–1887) and 14,8 × 109/l (range, 52–1887). 54,5% patients have a PMF diagnosis. JAK2V617F was present in 69,8% patients, CALR mutations in 15,4% and MPLW515K/L in 5,3%; 9,5%of the patients were triple negatives. In SMF patients the median values of age, leucocytes, hemoglobin and platelets were 66 years, 12,5x10e9/L, 10,7g/dl and 259x10e9/L respectively and in PMF patients 66 years, 8,9x10e9/L, 10,7x10e9/L and 243x10e9/L, without statistical differences between both groups. Fifty five patients were treated with ruxolitinib, 30 in PMF group and 25 in SMF group. 86% of patients had a response to this treatment.. The median survival at five years was 71%, 81% in SMF and 69% in PMF. In patients with CALR mutations, the survival was poor in PMF (34%) than in posthrombocitemic MF(80%) without differences in JAK2V617F mutated group.
Summary/Conclusion: Ruxolitinib is an effective treatment in PMF and SMF with a favorable impact in survival. 2.-In CARL mutated patients, the hematopoietic progenitor seems to be more sensitive to JAK2 pathway blocking when the disease has evolutioned from a previous ET although large studies are required to confirm these results.
Keywords: Myelofibrosis, Myeloid metaplasia, Idiopathic myelofibrosis