COMPARISON OF CLINICAL AND LABORATORY DATA, INCLUDING JAK-2 46/1 HAPLOTYPE, BETWEEN PATIENTS WITH IDIOPATHIC ERYTHROCYTOSIS AND POLYCYTHEMIA VERA.

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): A multicentre phase II clinical trial

Abstract A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37–73) and a median ECOG performance status of 1 (range 0–2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m 2 diluted in 250 cc 3 of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m 2 on days 1 and 8 every 4 weeks. The…

Detection and clinical implications of a novel BCR-ABL1 E12A2 insertion/deletion in a CML patient expressing the E13A2 isoform

Background/Aim: The Philadelphia chromosome is the most frequent cytogenetic abnormality in chronic myelogenous (CML). More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement. Furthermore, about 5% of CML patients are diagnosed with rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. However, there is limited evidence concerning the clinical and prognostic implications of these infrequent oncogenic variants for CML patients receiving tyrosine kinase inhibitors (TKIs). Case Report: We describe a novel atypical e12a2 insertion/deletion (In…

Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt

The Essential Thrombocythemia in 2020: What We Know and Where We Still Have to Dig Deep

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has …

Splenomegaly Impacts Prognosis in Essential Thrombocythemia and Polycythemia Vera: A Single Center Study

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

Isolated Nodal TBC Reactivation in a Patient with Post-Thrombocythemia Myelofibrosis Treated with Ruxolitinib: Case Report and Review of the Literature

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases descr…

Low-dose ponatinib is a good option in chronic myeloid leukemia patients intolerant to previous TKIs.

JAK2 ALLELE BURDEN IN PATIENTS WITH PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

Familial essential thrombocythemia: 6 cases from a mono‐institutional series

Rarely essential thrombocythemia (ET) is diagnosed in more than one person within a family. Familial myeloproliferative neoplasms are underdiagnosed. In this report, we describe 6 couples of familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.

Late onset of unilateral optic disk edema secondary to treatment with imatinib mesylate

Key Clinical Message Prompt ophthalmology evaluation and immediate imatinib suspension should be suggested at any time of tyrosine kinase inhibitor therapy in patients with visual deficit, as it may be a clinical manifestation of optic disk edema, and suspension may help in prompt recovery.

Antimicrobial prophylaxis in patients with immune thrombocytopenia treated with rituximab: a retrospective multicenter analysis

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according…

Cardiovascular Issues in Tyrosine Kinase Inhibitors Treatments for Chronic Myeloid Leukemia: A Review

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo wh…

Comparison between thrombotic risk scores in essential thrombocythemia and survival implications.

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. …

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience

<b><i>Background:</i></b> Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. <b><i>Methods:</i></b> A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with…

Efficacy of ruxolitinib retreatment in a patient with high-risk myelofibrosis using the international prognostic scoring system

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm in which clonal proliferation of hematopoietic stem cells and bone marrow fibrosis coexist.1 Patients may eventually die due to leukemic progression, which occurs in up to 20% of cases, or because of cardiovascular comorbidities or cytopenia, which causes susceptibility to infections and bleeding.2 Myelofibrosis diagnosis relies upon the evaluation of several clinical and laboratory criteria suggested by the World Health Organization (WHO) in 2016.3 The major mutations leading to myelofibrosis usually occur in the JAK2, CALR, and MPL genes. However, in almost 10% of the cases, none of the above-mentioned mutations can be detected …

Triple-Negativity Identifies a Subgroup of Patients with Better Overall Survival in Essential Thrombocythemia

Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed…

Essential thrombocythemia: Biology, clinical features, thrombotic risk, therapeutic options and outcome

CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL

Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to promoting the thrombotic event due to the interaction between platelets, leukocytes, and endothelium alterations. Moreover, a significant role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study, we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET .

The Essential Thrombocythemia, Thrombotic Risk Stratification, and Cardiovascular Risk Factors

Essential thrombocythemia is a rare hematological malignancy with good overall survival, but moderate to high risk of developing arterial or venous thrombosis lifelong. Different thrombotic risk scores for patients with essential thrombocythemia have been proposed, but only one of them (the IPSET-t scoring system) takes into account the classical cardiovascular risk factors as one of the scoring items. Currently, in clinical practice, the presence of cardiovascular risk factors in patients with diagnosis of ET rarely determines the decision to initiate cytoreductive therapies. In our study, we compared different risk models to estimate the thrombotic risk of 233 ET patients and the role of …

Coexistence of Von Willebrand disease and gastrointestinal stromal tumor (G.I.S.T): Case report of a rare and challenge association

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of Von Willebrand factor (VWF). Bleeding from the gastrointestinal (GI) tract is not uncommon in VWD and is usually associated with angiodysplasia. We report herein on the management of a patient affected by VWD2B with severe GI bleeding secondary to gastrointestinal stromal tumor (GIST) complicated by deep vein thrombosis (DVT). The current case demonstrated that the hemostatic balance, in RBDs under specific circumstances, can range from a tendency toward a hemorrhagic to normal or prothrombotic state. In these patients, a close collabor…

Age at diagnosis is an important prognostic factor in Philadelphia-negative Myeloproliferative Neoplasms

Cardiovascular Risk in Polycythemia Vera: Thrombotic Risk and Survival: Can Cytoreductive Therapy Be Useful in Patients with Low-Risk Polycythemia Vera with Cardiovascular Risk Factors?

<b><i>Background/Aims:</i></b> Cardiovascular risk factors are not considered in the current scores for evaluation of the thrombotic risk in myeloproliferative neoplasms, and in polycythemia vera (PV) in particular. Cytoreduction is currently not indicated in low-risk patients with PV, despite the absence or presence of cardiovascular risk factors. Our purpose is to highlight how cardiovascular risk factors in patients with PV increase the thrombotic risk both in low- and high-risk patients. <b><i>Methods:</i></b> We collected and analyzed data from 165 consecutive patients with a diagnosis of PV followed at our institution and compared the fr…

Doxorubicin-docetaxel sequential schedule: results of front-line treatment in advanced breast cancer.

<i>Objective:</i> We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer. <i>Methods:</i> A total of 73 patients with PS (ECOG) 0–2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m<sup>2</sup> by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m<sup>2</sup>, by i.v. 60 min infusion. Cycles were repeate…

Management of Ponatinib in Patients with Chronic Myeloid Leukemia with Cardiovascular Risk Factors

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hype…