Publications by authors named "Barbara Mora"

49 Publications

MYD88 Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation.

Diagnostics (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, Italy.

In IgM monoclonal gammopathies MYD88 is a prognostic and predictive biomarker of therapy response. MYD88 detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88 screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88 detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88 detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88 detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88 mutational levels observed between Waldenström Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenström.
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http://dx.doi.org/10.3390/diagnostics11050779DOI Listing
April 2021

Gene expression profile correlates with molecular and clinical features in patients with myelofibrosis.

Blood Adv 2021 Mar;5(5):1452-1462

Center for Genome Research.

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 with clinical and molecular detrimental features included in contemporary prognostic models, such as the presence of high molecular risk mutations. The high-risk group was enriched in post-PV and post-ET MF and JAK2V617F homozygous patients, whereas pre-PMF was more frequent in the low-risk group. These results demonstrate that GEPs in MF patients correlate with their molecular and clinical features, particularly their survival, and represent the proof of concept that GEPs might provide complementary prognostic information to be applied in clinical decision making.
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http://dx.doi.org/10.1182/bloodadvances.2020003614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948267PMC
March 2021

Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial.

Lancet Haematol 2021 Mar 18;8(3):e175-e184. Epub 2021 Jan 18.

Unità Operativa di Ematologia e Trapianto Midollo Osseo, IRCCS Ospedale San Raffaele, Milan, Italy.

Background: There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone.

Methods: In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18-60 years, with a diagnosis of polycythaemia vera according to 2008-16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 μg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov, NCT03003325.

Findings: Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0-12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7-41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred.

Interpretation: Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera.

Funding: AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro.
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http://dx.doi.org/10.1016/S2352-3026(20)30373-2DOI Listing
March 2021

Tuberculosis in elderly patients in the city of Cali, Colombia: a hospital-based cohort study.

J Bras Pneumol 2020 09 23;46(5):e20200072. Epub 2020 Sep 23.

. Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Universitat de Barcelona, Barcelona, España.

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http://dx.doi.org/10.36416/1806-3756/e20200072DOI Listing
September 2020

Is there a gender effect in polycythemia vera?

Ann Hematol 2021 Jan 2;100(1):11-25. Epub 2020 Oct 2.

Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy.

In recent times, there has been a growing interest in understanding the impact of gender on disease biology and clinical outcomes in Philadelphia-negative chronic myeloproliferative neoplasms. Among those, polycythemia vera (PV) is characterized by increased thrombotic risk, systemic symptoms, and overall reduced survival. Here, we aim to summarize data on whether and to what extent female sex can affect PV biology and outcome. To this end, we will discuss the latest acquisitions in terms of pathogenesis, diagnosis, epidemiology, clinical presentation and symptoms burden, thrombotic risk and related treatment strategies, and prognosis in female patients affected by PV.
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http://dx.doi.org/10.1007/s00277-020-04287-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782364PMC
January 2021

Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses.

Blood Adv 2020 08;4(15):3708-3715

Centre d'Investigations Cliniques (CIC) 1427, INSERM, Hôpital Saint-Louis, Université de Paris, Paris, France.

Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.
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http://dx.doi.org/10.1182/bloodadvances.2020002414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422133PMC
August 2020

Phylogenetic dating analysis of HTLV-1 from Chile suggests transmissions events related to ancient migrations and contemporary expansion.

Int J Infect Dis 2020 10 25;99:186-189. Epub 2020 Jul 25.

Laboratory Integrative Biology (LIBi), Center for Excellence in Translational Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile. Electronic address:

Human T-cell lymphotropic virus type 1 (HTLV-1) is a globally-spread virus. It is estimated that there are about 5–10 million infected people in the world. HTLV is endemic in Chile, with higher seroprevalence among indigenous people. However, little is known about HTLV-1 genetic diversity, its introduction and dispersion in this country. To gain insights into these issues, a phylogenetic dating analysis was conducted based on Chilean and closed related long terminal repeat sequences. The time tree reconstruction showed that the introduction of HTLV-1aA occurred several times in Chile. It was hypothesized that these introductions took place at least in two different historical moments: (i) during the ancient human migrations and (ii) during/after the European colonization of South America. The present study contributes toward understanding the evolutionary history of HTLV-1 in Chile and South America.
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http://dx.doi.org/10.1016/j.ijid.2020.07.037DOI Listing
October 2020

Recurrence of immune thrombocytopenia at the time of SARS-CoV-2 infection.

Ann Hematol 2020 08 11;99(8):1951-1952. Epub 2020 Jun 11.

Infectious and Tropical Diseases, University Hospital "Ospedale di Circolo e Fondazione Macchi" - ASST Sette Laghi, University of Insubria, Varese, Italy.

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http://dx.doi.org/10.1007/s00277-020-04130-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288620PMC
August 2020

Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma.

Leuk Lymphoma 2020 09 28;61(9):2122-2128. Epub 2020 Apr 28.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Recent studies have demonstrated feasibility and substantial benefit of direct-acting antivirals (DAAs) administration during or after first-line immune-chemotherapy (I-CT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphomas (DLBCL). However, data on DAAs used during or after salvage treatments are still lacking. In this study we assessed clinical and virological outcome in 11 patients with relapsed ( = 7) or refractory ( = 4) HCV-positive DLBCL. DAAs were given either concurrently ( = 3) or subsequent ( = 8) to salvage I-CT. Most patients (10 of 11) received sofosbuvir-based regimens. All patients completed their planned courses of DAAs and achieved sustained virological response. DAAs were well tolerated, with no grade ≥2 adverse events. At a median follow-up of 3.6 years four patients died (4-year OS: 76%). In conclusion, we provide evidence that DAAs in HCV-positive relapsed/refractory DLBCL are extremely safe and effective, suggesting that they should be used if HCV eradication was not instituted before.
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http://dx.doi.org/10.1080/10428194.2020.1755859DOI Listing
September 2020

Validation and further potentialities of the novel AWM score for progression risk stratification in patients with asymptomatic Waldenström macroglobulinemia.

Leuk Lymphoma 2020 04 14;61(4):987-989. Epub 2019 Nov 14.

Department of Hematology, University Hospital "Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi", University of Insubria, Varese, Italy.

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http://dx.doi.org/10.1080/10428194.2019.1689393DOI Listing
April 2020

Second primary malignancies in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 2233 patients.

Cancer Med 2019 08 7;8(9):4089-4092. Epub 2019 Jun 7.

Hematology, Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Patients with myeloproliferative neoplasms (MPN) are known to have higher incidence of nonhematological second primary malignancies (SPM) compared to general population. In the MYSEC study on 781 secondary myelofibrosis (SMF) patients, the incidence of SPM after SMF diagnosis resulted 0.98/100 patient-years. When including non-melanoma skin cancers (NMSC), the incidence arose to 1.56/100 patient-years. In SMF, JAK inhibitor treatment was associated only with NMSC occurrence. Then, we merged the MYSEC cohort with a large dataset of PV and ET not evolving into SMF. In this subanalysis, we did not find any correlation between SPM and SMF occurrence. These findings highlight the need of studies aimed at identifying MPN patients at higher risk of SPM.
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http://dx.doi.org/10.1002/cam4.2107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675726PMC
August 2019

A scoping review of transmission of dengue virus from donors to recipients after solid organ transplantation.

Trans R Soc Trop Med Hyg 2019 08;113(8):431-436

Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cra. 98 #18-49, Cali, Colombia.

Dengue virus can infect humans through vectorial and non-vectorial transmission. Classically, non-vectorial transmission has been related to vertical transmission and health care-associated infections, but recently transmission to solid organ and bone marrow recipients has been reported. We performed a scoping review of the available literature searching for evidence on screening for dengue in potential organ donors and the use of these infected organs. From 372 unique records identified, 17 were eligible to be included in our scoping study. After applying inclusion and exclusion criteria, three studies were included. These studies described a total of six patients from India (two case reports; n=2) and Colombia (one case series; n=4). Three patients received a liver, two received a kidney and one had a heart transplant. The onset of symptoms occurred in the first week after transplant in all cases and all experienced fever as the primary symptom. All patients presented thrombocytopenia with a platelet count <50 000. None of the patients developed graft rejection. However, four patients presented graft complications. No recipient deaths occurred. There is not a strong recommendation for dengue screening of donors in transplantation guidelines, but in endemic areas, physicians should be aware of this type of transmission before transplantation.
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http://dx.doi.org/10.1093/trstmh/trz024DOI Listing
August 2019

Developments in diagnosis and treatment of essential thrombocythemia.

Expert Rev Hematol 2019 03 13;12(3):159-171. Epub 2019 Mar 13.

a Ospedale di Circolo , ASST Sette Laghi, Hematology , Varese , Italy.

Introduction: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by thrombocytosis, increased risk of thrombotic/hemorrhagic events and clonal evolution into blast phase or myelofibrosis. Areas covered: The authors will discuss biology, diagnosis, prognosis, therapy, and outcome of ET. An accurate molecular-morphologic assessment is necessary in order to properly establish diagnosis and prognosis of ET. Stratification for thrombosis prediction is essential, and IPSET-t model is widely applied. The current treatment strategy is directed to lower the rate of vascular events using cytoreduction in patients at high risk. Prophylactic low dose aspirin indication is more uncertain. To date, therapies for patients who are resistant or intolerant to first-line treatments are scarce. Overall, life expectancy indicates an indolent disease, but IPSET model helps in predicting survival at the time of diagnosis. Expert opinion: Challenging for the future will be to share criteria for ET diagnosis with the community. New insights into the molecular pathogenesis of the disease will improve the prediction of clonal evolution and outcome, and lead to the use of disease-modifying treatments.
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http://dx.doi.org/10.1080/17474086.2019.1585239DOI Listing
March 2019

Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?

J Matern Fetal Neonatal Med 2020 Jul 9;33(14):2445-2450. Epub 2019 Jan 9.

Clinical Research Center, Fundación Valle Del Lili, Cali, Colombia.

There is lack of data on the management of severe dengue infection during labor. The objective of this study was to describe our experience in the management of preterm and term labor of pregnant patients with severe dengue infection and thrombocytopenia. We describe patients with dengue infection confirmed by dengue serology or NS1 antigen in Cali, Colombia. All of the patients had warning or severity signs for dengue and initiated labor, either term or preterm, during their hospital stay. All had thrombocytopenia at the moment labor started. Therefore, we treated them with support management, including intravenous fluids and a tocolytic agent (either atosiban, magnesium sulfate or nifedipine). Tocolytics aimed to stop contractions until platelets were in a safe range previous to delivery. Platelets transfusions were performed if the count was less than 10,000 cells/ml and active bleeding was present. The primary outcome we evaluated was postpartum hemorrhage (defined as a loss of >500 ml following a vaginal delivery or >1000 ml after cesarean section) or maternal and neonatal morbidity and mortality. We present a total of six pregnant women. The median platelet count 24 h previous to delivery was 94,000 cells/ml and after tocolysis was 132,500 cells/ml. Two patients suffered postpartum hemorrhage despite the management. Only one woman required platelet transfusion. No maternal or newborn mortality were present. Three patients were diagnosed with preeclampsia. Four patients had delivery cesarean section. Five out of six newborns required hospitalization, three of them due to neonatal respiratory distress syndrome. Comprehensive treatment including fluids resuscitation and uterine inhibition in pregnant women with severe dengue in preterm or term labor could be useful. More clinical studies are required to evaluate the benefit of this intervention in tropical countries. We present an original research article and literature review entitled "Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?". Our article describes the clinical manifestation, laboratory findings, complications and management provided to a group of six patients that presented to the hospital with acute dengue virus infection and initiated labor while viremic and thrombocytopenic in this study.In the present study, we found that most of our patients (5 out of 6), presented with signs of severe dengue fever and all of the patients had warning signs. In this population, we decided to provide support treatment and tocolytic agents to these patients with the aim of delaying labor to allow platelet count to rise, thus reducing the odds of hemorrhagic complications. We concluded that although tocolysis is not regularly used in patients with dengue fever, our results suggest that our protocol could benefit pregnant patients with thrombocytopenia due to dengue; however, prospective studies which determine the safety and effectiveness of our intervention are needed.
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http://dx.doi.org/10.1080/14767058.2018.1554044DOI Listing
July 2020

Invasive fungal infection by in immunocompetent hosts: A case series and literature review.

Med Mycol Case Rep 2019 Mar 25;23:12-15. Epub 2018 Oct 25.

Clinical Research Center, Fundación Valle del Lili, Carrera 98 #18-49, Cali, Colombia.

Invasive aspergillosis usually affects immunocompromised hosts with variable manifestations depending on the site of infection. In this article, we present two cases of invasive Aspergillosis in two non-immunocompromised patients; both cases had a paranasal sinuses infection, with intraorbital and intracranial extension, requiring surgery and antifungal treatment with Voriconazole. These cases were initially diagnosed as paranasal sinus neoplasms. However, the pathology and microbiology studies revealed invasive fungal infection by .
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http://dx.doi.org/10.1016/j.mmcr.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226581PMC
March 2019

Chikungunya in solid organ transplant recipients, a case series and literature review.

Transpl Infect Dis 2018 Dec 3;20(6):e12978. Epub 2018 Sep 3.

Infectious Diseases Service, Fundación Valle del Lili, Cali, Colombia.

Chikungunya virus is a recent emerging arbovirus in Latin America, and the clinical manifestations can vary from fever and rash to severe chronic inflammatory arthritis. Few reports have been published regarding this infection in immunocompromised patients, including solid organ transplant recipients. We report a case series of solid organ transplant recipients with confirmed Chikungunya infection by positive reverse transcription polymerase chain reaction (RT-PCR), identified between January 2014 and December 2016. In addition, we conducted a literature review searching PubMed, EMBASE, and LILACS databases on Chikungunya infection in solid organ transplant recipients. Ten solid organ transplant recipients were included, consisting of 5 kidney, 4 liver, and 1 liver/kidney transplant recipient. Mean age of the transplant recipients was 47 years, and the most frequent symptoms of Chikungunya infection were arthralgia and fever. None of the patients required treatment in the intensive care unit, no deaths or graft rejection occurred. None of our patients had recurrent arthritis during 3-month follow-up period after the infection. Twenty-one cases of Chikungunya virus were identified in the literature review. Most cases had a benign clinical course with no severe complications, death, or chronic inflammatory arthritis. In conclusion, Chikungunya infection in solid organ transplant recipients has a benign course and has no chronic recurrent arthritis. It is possible that the immunosuppression regimen could decrease the risk of severe or chronic inflammatory manifestations in solid organ transplant recipients infected with Chikungunya.
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http://dx.doi.org/10.1111/tid.12978DOI Listing
December 2018

Post-ET and Post-PV Myelofibrosis: Updates on a Distinct Prognosis from Primary Myelofibrosis.

Curr Hematol Malig Rep 2018 06;13(3):173-182

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Purpose Of Review: The purpose of this review is to help doctors in the management of patients with post-polycythemia (PPV) and post-essential thrombocythemia (PET) myelofibrosis (MF) facing diagnostic criteria, prognostication, and treatment possibilities.

Recent Findings: Diagnostic criteria of primary myelofibrosis (PMF) have been recently updated from the WHO classification. A clear-cut distinction between pre-fibrotic and overt PMF has been done. Concerning PPV and PET MF, the criteria come from 2008. Prognostication of PMF has been well established on clinical criteria, but recent molecular acquisitions will improve the strategy. For PPV and PET MF, the new MYSEC-PM is helpful for prediction of survival. JAK2-inhibitors and stem cell transplant are the two critical therapeutic approaches in myelofibrosis. Differences between PMF and SMF substantiate the efforts underway to adequately stratify SMF patients with ad hoc prognostic tools and to use such categorization to evaluate available treatment modalities.
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http://dx.doi.org/10.1007/s11899-018-0453-yDOI Listing
June 2018

Therapy of polycythemia vera: is it time to change?

Oncotarget 2017 Nov 3;8(61):102759-102760. Epub 2017 Nov 3.

Francesco Passamonti: Department of Medicine and Surgery, Hematology, University of Insubria, Varese, Italy and Ematologia, ASST Sette Laghi-Ospedale di Circolo, Varese, Italy.

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http://dx.doi.org/10.18632/oncotarget.22282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732684PMC
November 2017

Polycythemia vera: from new, modified diagnostic criteria to new therapeutic approaches.

Clin Adv Hematol Oncol 2017 Sep;15(9):700-707

Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi - Ospedale di Circolo, Varese, Italy.

Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm that is associated with a Janus kinase 2 (JAK2) mutation in most cases. The most recent update to the World Health Organization diagnostic criteria for PV was published in 2016. These were the modifications with the greatest effect: (1) lowering the hemoglobin threshold, allowing a diagnosis of PV at 16.5 g/dL in males and at 16.0 g/dL in females and (2) introducing a hematocrit cutoff (49% in males and 48% in females). Patients with PV who are older than 60 years or have had a previous thrombotic event are considered at high risk for thrombosis. Leukocytosis and a high allele burden are additional risk factors for thrombosis and myelofibrosis, respectively. After disease has progressed to post-polycythemia vera myelofibrosis (PPV-MF), survival must be assessed according to the recently developed Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM). This model is based on age at diagnosis, a hemoglobin level below 11 g/dL, a platelet count lower than 150 × 109/L, a percentage of circulating blasts of 3% or higher, a CALR-unmutated genotype, and the presence of constitutional symptoms. Therapy is based on phlebotomy to maintain the hematocrit below 45% and (if not contraindicated) aspirin. When a cytoreductive drug is necessary, hydroxyurea or interferon can be used as first-line therapy, although the demonstration of an advantage of interferon over hydroxyurea is still pending. In patients whose disease fails to respond to hydroxyurea, ruxolitinib is a safe and effective choice.
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September 2017

New molecular genetics in the diagnosis and treatment of myeloproliferative neoplasms.

Curr Opin Hematol 2016 Mar;23(2):137-43

aDepartment of Clinical and Experimental Medicine, University of Insubria bDivision of Hematology, Ospedale di Circolo, Varese, Italy.

Purpose Of Review: Myeloproliferative neoplasms (MPN) are conditions of great interest because of the identification of their molecular basis and of the entering of new small molecules into clinical practice. The aim of this review is to report the role of mutations in the diagnosis, prognosis, and in the prediction of response to JAK inhibitors in MPN.

Recent Findings: New mutations of the CALR gene have been discovered in patients without JAK2 or MPL mutations and are now included in the World Health Organization classification system. The role of ASXL1 and SRSF2 together with the driver mutations is emerging in the prognostication of myelofibrosis.

Summary: A wide mutational analysis of MPN helps to define diagnosis and prognosis. In the future, clinical trials based on a robust valuation of mutations will guide treatment decision-making towards precision medicine.
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http://dx.doi.org/10.1097/MOH.0000000000000218DOI Listing
March 2016

Comparative Analysis of Real-Time Polymerase Chain Reaction Methods to Typing HLA-B*57:01 in HIV-1-Positive Patients.

AIDS Res Hum Retroviruses 2016 07 10;32(7):654-7. Epub 2016 Feb 10.

1 Department of Molecular Medicine, Sapienza University of Rome , Rome, Italy .

The HLA-B*57:01 allele is strongly associated with the hypersensitivity reaction to Abacavir (ABC). Therefore, treatment guidelines recommend that patients initiating ABC are preventively tested for the presence of this allele. To date, four different commercial assays based on the real-time quantitative polymerase chain reaction (Q-PCR) technique are available for the detection of HLA-B*57:01: Duplicα-RealTime Reagent Set HLA-B*57:01 by Euroclone, HLA-B*57:01 Real-TM by Sacace Biotechnologies, COBAS AmpliPrep/COBAS TaqMan HLA-B*57:01 Screening Test by Roche Diagnostic, and HLA-B*57:01 by Nuclear Laser Medicine. The study was carried out to compare the performance of the first three commercially available Q-PCR kits in a routine clinical setting. A total of 98 samples from Policlinico Umberto I Hospital were tested. Results obtained by the Duplicα-RealTime Genotyping kit and AmpliPrep/TaqMan system were 100% concordant. In contrast, genotyping by the HLA-B*57:01 Real-TM kit showed poor agreement with the other systems, that is, 12 out of 33 positive samples were detected as HLA-B*57:01 negative. To confirm the correct genotype of these discordant samples, two additional methods with rapid turnaround times and already implemented into routine clinical practice were used, that is, a PCR-based microsequence-specific primer DNA typing test and a laboratory-developed screening test in Q-PCR. All 12 discordant samples were genotyped as HLA-B*57:01-positive samples using these two additional methods in a single-blinded manner, thus confirming the low sensitivity of HLA-B*57:01 Real-TM test. These findings underline the need to compare results obtained with commercial assays before choosing a test suitable for use in a routine clinical laboratory.
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http://dx.doi.org/10.1089/AID.2015.0303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931735PMC
July 2016