WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

The R package mice imputes incomplete multivariate data by chained equations. The software mice 1.0 appeared in the year 2000 as an S-PLUS library, and in 2001 as an R package. mice 1.0 introduced predictor selection, passive imputation and automatic pooling. This article documents mice, which extends the functionality of mice 1.0 in several ways. In mice, the analysis of imputed data is made completely general, whereas the range of models under which pooling works is substantially extended. mice adds new functionality for imputing multilevel data, automatic predictor selection, data handling, post-processing imputed values, specialized pooling routines, model selection tools, and diagnostic graphs. Imputation of categorical data is improved in order to bypass problems caused by perfect prediction. Special attention is paid to transformations, sum scores, indices and interactions using passive imputation, and to the proper setup of the predictor matrix. mice can be downloaded from the Comprehensive R Archive Network. This article provides a hands-on, stepwise approach to solve applied incomplete data problems.

/pdf/mice-multivariate-imputation-by-chained-equations-in-r-2cffzza5jj.pdf

mice: Multivariate Imputation by Chained Equations in R

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

https://www.chpso.org/sites/main/files/file-attachments/chest-2008-geerts-381s-453s.pdf

Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition)

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

New targeted therapies administered in phase II and phase III studies have produced substantial improvements in outcomes of myelofibrosis (MF). However, strong documentation that the new agents modify the natural history of the disease is lacking, and a number of therapeutic indications of new drugs remain unaddressed. Overall survival (OS) improvement is the major goal of next-generation clinical trials in MF. This may be attained if an adequate population of patients and an unambiguous design of the trial will be selected. Another goal is preventing disease progression in early MF: this requires a controlled clinical trial with an accessible endpoint and a clinically relevant definition of disease progression. Improvement in the documentation of responsiveness of patient-reported outcomes (PROs) will allow to use them as a critical endpoint of new trials. Finally, exploiting the clinical utility of biomarkers should become a major goal of future clinical experimentation in MF.

Setting Appropriate Goals for the Next Generation of Clinical Trials in Myelofibrosis.

Idiopathic pulmonary hemosiderosis: ferrokinetic remarks.

Context: Fedratinib is a selective JAK2/FLT3 inhibitor shown to induce spleen responses and symptom improvement in patients with myelofibrosis. Gastrointestinal (GI) events including nausea, vomiting, and diarrhea, were the most common adverse events (AEs) in fedratinib clinical trials, and were most frequent during early treatment. The JAK1/2 inhibitor, ruxolitinib, has demonstrated efficacy in patients with myelofibrosis; however, many patients discontinue ruxolitinib due to loss of response or drug-related cytopenias. The ongoing, single-arm, phase IIIb FREEDOM study evaluates fedratinib in myelofibrosis patients previously treated with ruxolitinib. FREEDOM includes prospective mitigation strategies for managing GI events. Objective: Review the frequency, severity, and mitigation of GI events during early fedratinib treatment in FREEDOM. Methods: Eligible patients are aged ≥18 years, with intermediate- or high-risk MF, ECOG-PS score 0-2, platelet count ≥50 × 109/L, and splenomegaly ≥ 450cm3 or palpable spleen > 5 cm below LCM; and had previously received ruxolitinib for ≥3 months (or ≥28 days with intolerance). Patients receive fedratinib 400 mg/day in continuous 28-day cycles. Study design includes mitigation strategies (prophylaxis, symptomatic treatment, dosing modifications, dosing with food) for managing GI toxicities. AEs are evaluated in all treated patients. Results: At data cutoff (26-Mar-2020), 22 patients had enrolled; 4 patients discontinued (none due to GI-related events). Median age was 68.5 years (range, 49-80). All patients had received ≥3 months of prior ruxolitinib treatment; the most common reason for ruxolitinib discontinuation was relapse (27%). Median fedratinib treatment duration was 18.6 weeks (1.6-48); 10 patients (46%) received >6 fedratinib cycles. Diarrhea, vomiting, and nausea occurred in 32%, 18%, and 14% of patients, respectively; none of these events were grade 3-4 or required dose modification or discontinuation. 12 patients (55%) received ondansetron and 6 (27%) received loperamide. Conclusions: Fedratinib was generally well tolerated. In similar patients receiving fedratinib 400 mg/day (starting dose) in the phase II JAKARTA2 study, which did not prespecify mitigation for GI events, rates of diarrhea, nausea, and vomiting through end-of-cycle 6, ranged from 41% to 62%. Early data from the FREEDOM study suggest frequency and severity of GI events may be reduced via mitigation strategies. Study enrollment is ongoing.

MPN-183: Preliminary Gastrointestinal Safety and Tolerability of Fedratinib from the Phase IIIb FREEDOM Trial in Patients with Intermediate- or High-Risk Myelofibrosis Previously Treated with Ruxolitinib

Giovanni Barosi

Papers

Setting Appropriate Goals for the Next Generation of Clinical Trials in Myelofibrosis.

Idiopathic pulmonary hemosiderosis: ferrokinetic remarks.

MPN-183: Preliminary Gastrointestinal Safety and Tolerability of Fedratinib from the Phase IIIb FREEDOM Trial in Patients with Intermediate- or High-Risk Myelofibrosis Previously Treated with Ruxolitinib

Risk factors for elastic transformation in myelofibrosis with myeloid metaplasia (MMM)

Clonal Origin of Circulating Endothelial Progenitor Cells in Patients with Myelofibrosis with Myeloid Metaplasia.