Papers by Carmela Mannarelli
Blood, Dec 7, 2017
Background: The International Prognostic Scoring System (IPSS) (Blood 2009;113:2895), the dynamic... more Background: The International Prognostic Scoring System (IPSS) (Blood 2009;113:2895), the dynamic(D) IPSS (Blood 2010;115:1703) and the DIPSS-plus (JCO 2011;29:392) are commonly used to predict survival among patients (pts) with Primary Myelofibrosis (PMF). These scores were developed using populations of PMF pts that differ from the 2 categories outlined in the 2016 WHO criteria, i.e. prefibrotic and overt PMF (Blood 2016; 127:2391) ; indeed, IPSS performed suboptimally when applied to the two PMF variants (Blood 2017; 129:3227) . The prognostic relevance of fibrosis grade and mutation profile, including both driver (JAK2/CALR/MPL) and other myeloid malignancies-associated genes (Blood 2017; 129:3227), has been shown. Furthermore, high molecular risk category (HMR), including pts with any one mutated genes of ASXL1, SRSF2, EZH2, IDH1/2 (Leukemia 2013; 27:1861), and unfavorable karyotype (JCO 2011;29:392) , both provided IPSS/DIPSS-independent prognostic information for overall survival (OS) and leukemia-free survival (LFS). The aim of current study was to develop an updated prognostic score that included molecular (MIPSS70) and, when available, cytogenetic information (MIPSS70-plus), specifically directed to pts with pre-PMF and overt-PMF 70yr old and younger that are potential candidates to stem cell transplantation (SCT). Methods: Previously published methods were used to sequence JAK2, MPL, CALR, EZH2, ASXL1, IDH1/2 and SRSF2 . Survival was calculated from date of diagnosis (AGIMM cohort) or date of first referral (Mayo cohort). A Cox model with a stepwise selection procedure was used to select covariates significant for OS. The prognostic model was developed based on the magnitude of the hazard ratios (HR) in the training cohort. Results: Development of MIPSS70. The learning cohort included 490 pts aged 2 HMR mutated genes. A HR-weighted score was assigned to variables maintaining significance in multivariable analysis: 2.0 points to leukocytes >25x109/L, platelets 2 HMR mutations; 1.0 point to hemoglobin 2, absence of CALR type1/like, HMR category. Accordingly, 3 risk categories were delineated (Fig 1A): Low (score 0-1); Intermediate(score 2-4); and High (score >5) with 10-y survival of 83%, 39% and 12%, respectively. MIPSS70 yielded a better prediction of OS in a ROC analysis (MIPSS70 AUC = 0.760 vs. IPSS AUC = 0.710). Significantly different (p 70y in both cohorts. Development of MIPSS70-plus.The learning cohort included 209 cytogenetically-annotated pts, aged ≤70y, from Mayo Clinic. Unfavorable vs favorable karyotype was added to the multivariable model that included all 8 MIPSS70 variables. Unfavorable karyotype (HR 2.6), presence of one (HR 1.7) or ≥2 (HR 2.3) HMR mutations, absence of type1/like CALR (HR 2.2), constitutional symptoms (HR 2.4), circulating blasts ≥2% (HR 1.7) and hemoglobin 70y. Conclusions. The new MIPSS70 and MIPSS70-plus scores include modern disease-associated, risk variables pertinent to both pre-PMF and overt-PMF according to the 2016 WHO classification, and are intended to facilitate decision-making for patients 70yr old and younger who are potential candidates to SCT. Disclosures Vannucchi: Novartis: Honoraria, Speakers Bureau; Shire: Speakers Bureau. Rambaldi: Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses; Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy. Passamonti: Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Speakers Bureau.
Blood, Nov 15, 2022
Background The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated inter... more Background The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment. Methods PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, openlabel, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 µg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing). Findings Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182•1 weeks (IQR 166•3-201•7) in the ropeginterferon alfa-2b and 164•5 weeks (144•4-169•3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0•044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0•63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0•012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia). Interpretation In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea.
Blood Cancer Journal, Jan 30, 2023
Unfavorable karyotype indicates any abnormal karyotype other than normal karyotype or sole abnorm... more Unfavorable karyotype indicates any abnormal karyotype other than normal karyotype or sole abnormalities of 20q-, 13q-, +9, chromosome 1 translocation/duplication,-Y or sex chromosome abnormality other than-Y. Bold values denote statistical significance at the p < 0.05 level.
Blood, Nov 5, 2021
Background: Thrombosis is the main cause of morbidity and mortality in pts with Polycythemia Vera... more Background: Thrombosis is the main cause of morbidity and mortality in pts with Polycythemia Vera (PV). Current risk stratification is based on 2 variables: age &gt;60y and history of thrombosis. Additional thrombotic risk factors in PV are generic cardiovascular risk factors and leukocytosis. JAK2V617F (JAK2VF) variant allele frequency (VAF) at diagnosis is highly heterogeneous. A VAF&gt;75% was associated with higher rate of all thrombosis after diagnosis (Vannucchi AM et al, Leukemia 2007), and a VAF ≥ 60% correlated with increased rate of venous thrombosis (VT) in high-risk pts (Guglielmelli P et al, ASH 2018); however, predictive role of JAK2VF VAF is still debated. Aim: To evaluate the impact of JAK2VF VAF on rate of arterial and venous thrombosis in PV pts. Patients and methods: A cohort of 576 strictly 2016 WHO-defined PV pts followed at Univ. of Florence (1981-2020) were included. All pts were annotated for JAK2VF VAF, determined &lt;3 years from diagnosis, and thrombosis at diagnosis and follow-up (FU). Arterial thromboses (AT) included stroke, transient ischemic attacks, retinal artery occlusion, coronary artery disease, and peripheral arterial disease; VT included cerebral venous thrombosis, deep vein thrombosis, pulmonary embolism. Splanchnic vein thromboses (SVT) were excluded. Only first occurring event was considered. Cox proportional hazard regression model was used for univariate and multivariable analysis. Kaplan-Meier (KM) analysis was used for time-to-event assessment, compared by log-rank test. Results: Median age was 61.4 y (range, 16.2-91.8), 58.2% were male; 62% were high-risk based on current classification. Median JAK2VF VAF was 41.5% (range, 0.3-100). A total of 76 (13.2%) pts had an AT event before/at PV diagnosis and 49 (8.5%) pts had an AT during FU. As regards VT, 64 (11.1%) and 39 (6.8%) pts had a VT before/at or after PV diagnosis, respectively. We found that JAK2 VAF as a continue variable was correlated with the risk of VT in FU (p=0.003) but not with AT (p=0.8). ROC analysis to determine the best cut-off level for JAK2 VAF predicting VT had an AUC of 0.72 and a best cut-off value of VAF=50%. VT at FU were significantly enriched in pts with VAF &gt;50%: 14.5% versus 2.4%, p=&lt;0.0001. VT -free survival (VT-FS) by KM was significantly shorter in the presence of a JAK2 VAF &gt;50% (HR 4, CI 1.9-8.6, p&lt;0.0001) (Figure 1A), whereas no difference was found for AT (HR 0.9). In addition to JAK2VF VAF&gt;50%, univariate analysis for VT-FS identified history of VT (HR 2.9; CI 1.4-6.1, p=0.006), leukocytosis ≥11x10 9/L (HR 1.9; CI 1.1-3.4, p=0.02) and palpable splenomegaly (HR 1.9, CI 1-3.6; p=0.04) as risk factors. Multivariable analysis confirmed VAF&gt;50% (HR 3.8, CI 1.8-8.1, p=0.0006) and previous VT (HR 2.4, CI 1.1-5.1; p=0.02) as independent risk factors for future VT. In contrast, univariate analysis for AT-free survival (AT-FS) identified history of AT (HR 2.5; CI 1.3-4.9, p=0.007), diabetes (HR 3.3; CI 1.6-6.5, p=0.0007), hyperlipidemia (HR 3.1; CI 1.7-5.6, p=0.0003) and hypertension (HR 2, CI 1.1-3.8; p=0.03) as predictors of future AT; age &gt;60y showed only a trend (p=0.08). Multivariable analysis for AT-FS identified diabetes (HR 2.4, CI 1.2-5; p=0.02), hyperlipidemia (HR 2.3; CI 1.2-4.3, p=0.01) and previous AT (HR 2.1, CI 1-4.2; p=0.04) as independent predictors of future AT. Validation: Our findings were validated in an independent cohort of 315 2016-WHO defined PV pts from Policlinico Gemelli, Catholic Univ., Rome. After exclusion of 26 pts with SVT, analysis was conducted on 289 pts, 38 of them with thrombosis as heralding event (21 AT and 17 VT). Multivariable analysis confirmed JAK2VF VAF &gt;50% (HR 2.3, CI 1.03-5.0, p=0.04) and previous VT (HR 4.5, CI 2.0-10.1; p=0.0003) as independent risk factors for future VT. In pts with VAF &gt;50%, the rate of VT at FU was 19.9% vs 7.7%, P=0.005. KM curve showed that VT-FS was significantly shorter in pts with a JAK2VF VAF &gt;50% (HR 2.2, CI 1.2-4.2; p=0.01) (Figure 1B). Of note, impact of JAK2 VAF&gt;50% on VT at FU was statistically significant particularly in conventionally low-risk pts, accounting for an HR of 9.4 (CI 1.2-72) and HR 3.6 (CI 1.3-10) in Florence and Rome cohorts, respectively. Conclusions: These data support JAK2VF VAF as a strong independent predictor for future venous thrombosis in PV, in association with history of prior venous events, reinforcing that AT and VT are associated with unique risk factors in pts with PV. Supported by AIRC, Project Mynerva n.21267 Figure 1 Figure 1. Disclosures Vannucchi: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees.
Blood, Jun 27, 2019
and more likely to result in viral suppression compared with lamivudine. 8 Retrospective studies ... more and more likely to result in viral suppression compared with lamivudine. 8 Retrospective studies have shown that tenofovir may be more effective than entecavir in patients with positive hepatitis B e-antigen, but this was not tested in the 2 patients included in this series. 9 As B-cell aplasia can be prolonged and there are no data at this time on T-cell immune reconstitution after anti-CD19 CAR T-cell therapy, antiviral prophylaxis may need to be continued long-term, as suggested by HBV reactivation experienced by the patient who self-discontinued entecavir 1 year after therapy. The small sample size does not allow us to determine any association between concomitant HBV or HCV infection and CRS or CRES. Although the etiology of these entities remains to be fully clarified, both seem to be cytokine-driven, with interleukin 6 (IL-6) representing a key molecule. 10 Patients with chronic HBV or HCV infection have higher IL-6 production than healthy controls and all 3 patients discussed herein were treated with anti-IL-6 therapy for CRS/CRES. 11 Future studies will help to clarify the impact of chronic HBV/HCV infection on the risk of CRS and CRES.
Blood, Nov 5, 2021
Introduction: Myelofibrosis -either primary (PMF) or post-polycythemia vera/essential thrombocyth... more Introduction: Myelofibrosis -either primary (PMF) or post-polycythemia vera/essential thrombocythemia (collectively, secondary MF [SMF])- is characterized by biologic and clinical heterogeneity, with some patients (pts) presenting with features of myeloproliferation (MyP) and others exhibiting a myelodepletive (MyD) phenotype. Although not well defined, the latter is marked by cytopenias involving one or more hematopoietic lineages, in some respects mimicking a myelodysplastic or bone marrow (BM) failure syndrome. MyD features have been associated with poor prognosis in patients with MF, but cytopenias have been usually considered individually. In the current study, we aimed at investigating the phenotypic and prognostic correlates of a MyD phenotype in a large cohort of MF patients. Methods: After IRB approval, 704 consecutive patients with WHO-defined MF referring to CRIMM (Florence), were included in the study. There were 442 (63%) PMF and 262 (37%) SMF. Cytopenias at diagnosis were defined as follows: white blood cell (WBC) &lt;4×10 9/L, hemoglobin (Hb) &lt;11 g/dL for male and &lt;10 g/dL for female, platelets (Plt) &lt;100×10 9/L. A MyD phenotype was defined by the presence of at least one cytopenia in the absence of any increase of other blood cells (WBC &gt;15×10 9/L, Hb &gt;16.5 g/dL for male and &gt;16 g/dL for female, Plt &gt;450×10 9/L). Pts not included in the MyD group were considered as having a MyP phenotype. Mutational analysis by targeted NGS was available for 594/704 patients (PMF 368/442; SMF 226/262). Results: Overall, 166 pts were diagnosed as having a MyD MF, including 108 (24%) PMF and 58 (22%) SMF. Among PMF patients, leukopenia, sex-adjusted anemia and thrombocytopenia were present in 38%, 84% and 35%, respectively; in SMF, corresponding figures were 24%, 91% and 24%. Two or more cytopenias were found in 11% and 6% of PMF and SMF patients, respectively. In PMF, a MyD phenotype was associated with male gender (P=.0468), older age (P=.0002), lower peripheral blast count (P=.0006), higher prevalence of splenomegaly (P=0.0142), constitutional symptoms (P&lt;.0001), and BM fibrosis grade ≥2 (P&lt;.0001). The rates of thrombosis and bleeding were not different compared to MyP PMF. MyD pts were more likely to have very high risk (VHR) karyotype abnormalities (P=.0002) and to be triple negative (TN; P&lt;.0001); there were no correlations with JAK2 mutation status and mutant burden, CALR and MPL mutations. Among non-driver mutations, a MyD phenotype was significantly enriched in ASXL1 (P=.0074), IDH1/2 (P=0.064), N/KRAS (P=.0014), U2AF1 (P&lt;.0001), and CUX1 (P=.0002) mutations. Karyotype abnormalities (P=.0084), VHR cytogenetics (P=.0343), CBL (P=.0.171) and U2AF1 (P=.0148) mutations were significantly enriched in MyD pts with ≥2 cytopenias. On univariate analysis, OS was significantly shorter in pts with MyD vs MyP PMF (median, 55 vs 103 months, respectively; P&lt;.0001), and not different between MyD pts with one (median, 65 months) and ≥2 (median, 44 months) cytopenias (Fig. 1A). After competing risk analysis, the cumulative incidence of leukemic transformation (LT) was not different between MyD and MyP phenotypes (16% vs 11% at 5 years, respectively). Phenotypic differences between MyD and MyP patients were less evident in SMF, a part for older age of the former (P=.0207). The molecular background was likewise different: a MyD feature was enriched in mutations in TP53 (P=.0024), U2AF1 (P&lt;.0001), and SETBP1 (P=.0125). TP53 mutations were remarkably more frequent in MyD SMF pts with ≥2 cytopenias (19%). Pts with MyD SMF had a significantly shorter OS compared to the MyP counterpart (median, 44 vs 105 months; P&lt;.0001). Median OS was significantly inferior in MyD patients with ≥2 cytopenias compared to one cytopenia (median, 27 vs 58 months, respectively; P&lt;.0001) (Fig. 1B). The cumulative incidence of LT was not different: 16% vs 7% at 5 years, respectively, for SMF pts with MyD and MyP phenotype. Conclusion: The current study provides a comprehensive analysis of the MyD phenotype in pts with PMF and SMF, partly recapitulating findings of previous studies (Marcellino BK et al. Clin Lymphoma Myeloma Leuk 2020). We showed that the MyD phenotype is associated with high-risk clinical and molecular features, particularly in PMF, and correlates with inferior OS. Of interest, U2AF1 mutations emerged as a distinct molecular marker of MyD in both PMF and SMF, while mutations in TP53 appear prevalent in MyD SMF. Figure 1 Figure 1. Disclosures Vannucchi: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees.
Leukemia, Jul 12, 2017
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megaka... more Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1.
Blood Cancer Journal
Unfavorable karyotype indicates any abnormal karyotype other than normal karyotype or sole abnorm... more Unfavorable karyotype indicates any abnormal karyotype other than normal karyotype or sole abnormalities of 20q-, 13q-, +9, chromosome 1 translocation/duplication,-Y or sex chromosome abnormality other than-Y. Bold values denote statistical significance at the p < 0.05 level.
American Journal of Hematology
Blood Cancer Journal
Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients wit... more Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p < 0.0001), whereas no difference was found for AT (HR 0.9; p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4;...
☯ These authors contributed equally to this work. ‡ These authors also contributed equally to thi... more ☯ These authors contributed equally to this work. ‡ These authors also contributed equally to this work as last authors.
Blood Advances, 2020
The dysregulation of the JAK/STAT pathway drives the pathogenesis of myelofibrosis (MF). Recently... more The dysregulation of the JAK/STAT pathway drives the pathogenesis of myelofibrosis (MF). Recently, several JAK inhibitors (JAKis) have been developed for treating MF. Select mutations (MTs) have been associated with impaired outcomes and are currently incorporated in molecularly annotated prognostic models. Mutations of RAS/MAPK pathway genes are frequently reported in cancer and at low frequencies in MF. In this study, we investigated the phenotypic, prognostic, and therapeutic implications of NRASMTs, KRASMTs, and CBLMTs (RAS/CBLMTs) in 464 consecutive MF patients. A total of 59 (12.7%) patients had RAS/CBLMTs: NRASMTs, n = 25 (5.4%); KRASMTs, n = 13 (2.8%); and CBLMTs, n = 26 (5.6%). Patients with RAS/CBLMTs were more likely to present with high-risk clinical and molecular features. RAS/CBLMTs were associated with inferior overall survival compared with patients without MTs and retained significance in a multivariate model, including the Mutation-Enhanced International Prognostic...
Blood Advances, 2021
Myelofibrosis (MF) belongs to the family of classic Philadelphia-negative myeloproliferative neop... more Myelofibrosis (MF) belongs to the family of classic Philadelphia-negative myeloproliferative neoplasms (MPNs). It can be primary myelofibrosis (PMF) or secondary myelofibrosis (SMF) evolving from polycythemia vera (PV) or essential thrombocythemia (ET). Despite the differences, PMF and SMF patients are currently managed in the same way, and prediction of survival is based on the same clinical and genetic features. In the last few years, interest has grown concerning the ability of gene expression profiles (GEPs) to provide valuable prognostic information. Here, we studied the GEPs of granulocytes from 114 patients with MF, using a microarray platform to identify correlations with patient characteristics and outcomes. Cox regression analysis led to the identification of 201 survival-related transcripts characterizing patients who are at high risk for death. High-risk patients identified by this gene signature displayed an inferior overall survival and leukemia-free survival, together...
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Papers by Carmela Mannarelli