Publications (47) View all
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Article: Leukemia risk models in primary myelofibrosis: an International Working Group study.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2012; 26(6):1439-41. · 8.30 Impact Factor -
Article: Mutations and prognosis in primary myelofibrosis.
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ABSTRACT: Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL, and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; P<0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P=0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations. Mutational profiling for ASXL1, EZH2, SRSF2, and IDH identifies PMF patients who are at risk for premature death or leukemic transformation.Leukemia accepted article preview online, 26 April 2013; doi:10.1038/leu.2013.119.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; · 8.30 Impact Factor -
Article: LETTER TO THE EDITOR: Central nervous system relapse in acute promyelocytic leukemia: a single institution experience.
Leukemia & lymphoma 03/2013; · 2.40 Impact Factor -
Article: Plasma cytokines in polycythemia vera: Phenotypic correlates, prognostic relevance, and comparison with myelofibrosis.
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ABSTRACT: Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL-12 with hematocrit; IL-1b, IL-2, IL-7, FGF-b, and HGF with leukocytosis; and IFN-α and IFN-γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP-1β remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP-1β (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.American Journal of Hematology 06/2012; 87(11):1003-5. · 4.67 Impact Factor -
Article: Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria.
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ABSTRACT: In an international study of 1104 patients with essential thrombocythemia (ET), a histological review according to the 2008 World Health Organization (WHO) criteria confirmed ET in 891 patients (WHO-ET, 81%), and revised the diagnosis to prefibrotic primary myelofibrosis (PMF) in 180 patients (PMF, 16%). Major bleeding during follow-up occurred in 55 (6%) WHO-ET and 21 (12%) PMF patients (P = 0.009), at a rate of 0.79 and 1.39% patients per year, respectively, (P = 0.039). In a multivariable analysis, predictors of bleeding included diagnosis of PMF (P = 0.05; hazard ratio (HR) 1.74), leukocytosis (P = 0.04; HR 1.74), previous hemorrhage (P = 0.025; HR 2.35) and aspirin therapy (P=0.001; HR 3.16). The analysis restricted to patients with WHO-ET confirmed previous hemorrhage (P = 0.043; HR 1.92) and aspirin (P=0.027; HR 2.24) as independent risk factors. The current study reveals that major bleeding associated with thrombocytosis might be relatively specific to PMF, as opposed to WHO-defined ET. Furthermore, it shows that low-dose aspirin exacerbates these hemorrhagic events of PMF. In contrast, thrombocytosis per se was not a risk factor for bleeding; however, low-dose aspirin had a synergistic hemorrhagic effect unmasking the bleeding tendency of patients with extreme thrombocytosis. These observations carry significant therapeutic implications in these two WHO entities.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2011; 26(4):716-9. · 8.30 Impact Factor
