Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study.

Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET MF.

Impact of comorbidities and body mass index in patients with myelofibrosis treated with ruxolitinib.

Comorbidities defined by the Charlson comorbidity index (CCI) and body mass index (BMI) are significantly associated with outcome in patients who receive continuous treatment with tyrosine kinase inhibitors. We evaluated the impact of CCI and BMI on responses, drug-related toxicities, and outcome in a cohort of 402 patients with myelofibrosis (MF) treated with ruxolitinib in 23 European Hematology Centers. Comorbidities were evaluable in all 402 patients.

Ruxolitinib in elderly patients with myelofibrosis: impact of age and genotype. A multicentre study on 291 elderly patients.

Ruxolitinib is a JAK1/2 inhibitor that may control myelofibrosis (MF)-related splenomegaly and symptoms and can be prescribed regardless of age. While aging is known to correlate with worse prognosis, no specific analysis is available to confirm that ruxolitinib is suitable for use in older populations. A clinical database was created in 23 European Haematology Centres and retrospective data on 291 MF patients treated with ruxolitinib when aged ≥65 years were analysed in order to assess the impact of age and molecular genotype on responses, toxicities and survival.

A realist review to understand the efficacy and outcomes of interventions designed to minimise, reverse or prevent the progression of frailty.

Interventions to minimise, reverse or prevent the progression of frailty in older adults represent a potentially viable route to improving quality of life and care needs in older adults. Intervention methods used across European Innovation Partnership on Active and Healthy Ageing collaborators were analysed, along with findings from literature reviews to determine 'what works for whom in what circumstances'. A realist review of FOCUS study literature reviews, 'real-world' studies and grey literature was conducted according to RAMESES (Realist and Meta-narrative Evidence Synthesis: Evolving Standards), and used to populate a framework analysis of theories of why frailty interventions worked, and theories of why frailty interventions did not work.

Residual Peripheral Blood CD26 Leukemic Stem Cells in Chronic Myeloid Leukemia Patients During TKI Therapy and During Treatment-Free Remission.

Chronic myeloid leukemia (CML) patients in sustained "deep molecular response" may stop TKI treatment without disease recurrence; however, half of them lose molecular response shortly after TKI withdrawing. Well-defined eligibility criteria to predict a safe discontinuation up-front are still missing. Relapse is probably due to residual quiescent TKI-resistant leukemic stem cells (LSCs) supposedly transcriptionally low/silent and not easily detectable by BCR-ABL1 qRT-PCR.

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1.

Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: the possible role of ponatinib.

Introduction: In spite of the proven efficacy of the tyrosine kinase inhibitor (TKI), imatinib, in chronic myeloid leukemia (CML), many patients develop intolerance and discontinue therapy in the long-term. Second-generation TKIs (dasatinib, nilotinib, bosutinib) and the third-generation TKI, ponatinib, have added opportunities but also complexity in the settings of CML treatment.

Areas Covered: Different definitions of intolerance have been used through several clinical trials, making the published data non homogenous.

Miracle of haemophilia drugs: Personal views about a few main players.

Introduction: In the second decade of the third millennium there have been dramatic developments pertaining to the availability of highly innovative drugs for hemophilia care, notwithstanding a satisfactory previous scenario.

Aim: I am going to emphasize the role of 2 main categories of players: scientist physicians who produced important translational research and the pharmaceutical industry, who developed, produced and made commercially available so many improved treatment weapons stemming from the translational research of the forementioned scientist physicians.

Results: Pertaining to the role of scientist physicians, I chose to mention first those who were successful in the 1980 in the production of recombinant coagulation factors.

Ponatinib as second-line treatment in chronic phase chronic myeloid leukemia patients in real-life practice.

Scarce information is available on the use of ponatinib as second-line treatment in chronic phase chronic myeloid leukemia (CP-CML) patients resistant and/or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. We collected data from 29 CML patients, with a median age of 54 years (range 32-72). Eleven patients had received dasatinib, 15 patients received nilotinib, and 3 patients received imatinib as first-line treatment.

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients.

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib ( = 95) or nilotinib ( = 68) as second-line therapy after imatinib.

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms.

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.

Life for patients with myelofibrosis: the physical, emotional and financial impact, collected using narrative medicine-Results from the Italian 'Back to Life' project.

Purpose: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterised by an aggressive clinical course, with disabling symptoms and reduced survival. Patients experience a severely impaired quality of life and their families face the upheaval of daily routines and high disease-related financial costs. The aim of this study was to investigate the perceptions of Italian patients and their caregivers about living with MF and the burden of illness associated with MF.

Viral safety of coagulation factor concentrates: memoirs from an insider.

The purpose of this essay is to recall the actions taken globally to improve the viral safety of coagulation factor concentrates, mainly in the years 1985-1990, at a time of confusing and often contradictory information on bloodborne viral infections in multitransfused patients with hemophilia (PWHs). I shall first recall the problem of the transmission and control of the hepatitis viruses, and then that of HIV: not only for temporal reasons, but also because understanding the progress of knowledge on hepatitis and the poor success of the early measures taken to tackle this problem in PWHs is essential to understand how the problem of HIV transmission was ultimately dealt with successfully.

The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells.

Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context.

Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment.

Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined.

Objective: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions.