Genomic characterization and prognostication applied to a Brazilian cohort of patients with myelofibrosis.

Genomic characterization of patients with myeloproliferative neoplasms (MPN) may lead to better diagnostic classification, prognostic assessment, and treatment decisions. These goals are particularly important in myelofibrosis (MF). We performed target Next Generation Sequencing for a panel of 255 genes and Chromosome Microarray Analysis (CMA) in 27 patients with MF. Patients were classified according to genomic findings and we compared the performance of a personalized prognostication system with IPSS, MIPSS70 and MIPSS70 + v2. Twenty-six patients presented mutations: 11.1% had single driver mutations in either JAK2, CALR or MPL; 85.2% had mutations in non-restricted genes (median: 2 per patient). CMA was abnormal in 91.7% of the 24 cases with available data. Copy-Number-Neutral Loss-of-Heterozygosity was the most common finding (66.7%). Del13q was the most frequent copy number variation, and we could define a 2.4 Mb minimally affected region encompassing RB1, SUCLA2 and CLLS2 loci. The largest genomic subgroup consisted of patients with mutations in genes involved with chromatin organization and splicing control (40.7%) and the personalized system showed better concordance and accuracy than the other prognostic systems. Comprehensive genomic characterization reveals the striking genetic complexity of MF and, when combined with clinical data, led, in our cohort, to better prognostication performance.

Application of five prognostic survival scores to primary myelofibrosis in 62 Brazilian patients.

Primary myelofibrosis (PM) is a Philadelphia-negative clonal hematopoietic stem cell disorder characterized by intense reactive changes of bone marrow stroma with collagen fibrosis, osteosclerosis and angiogenesis. PM usually affects elderly people, and approximately half of the patients present JAK2V617F mutation. PM clinical course varies from 1 to 30 years, evolving from asymptomatic into progressive bone marrow failure, symptomatic splenomegaly or acute leukemia in 10-20 % of cases. PM risk stratification is based on parameters predicting survival, and several attempts have been made to identify clinical and laboratory features that could predict PM patient survival. This study applied five prognostic scores: Dupriez, Cervantes, Mayo, IPSS and DIPSS-Plus in 62 Brazilians patients from three centers, and compared their relevance and clinical usefulness considering the scores' parameters, fibrosis, JAK2V617F mutation, splenomegaly, hepatomegaly and treatment. According to the Cervantes, Dupriez and Mayo scores, most patients were stratified into low-risk group. However, when IPSS and DIPSS-Plus were applied, most patients were classified into an intermediate range, being low risk in only 11 and 13 % of patients, respectively. Overall survival at 4 years was 84 %. The Cervantes score was the only one that remained significantly associated with survival in a multivariate analysis. In conclusion, the Cervantes score remains important to the prognostication of PM.