Essential thrombocythemia, a myeloproliferative neoplasm, is associated with increased platelet count and risk of thrombosis or hemorrhage. Cytoreductive therapy aims to normalize platelet counts despite there being only a minimal association between platelet count and complication rates. Evidence is increasing for a correlation between WBC count and thrombosis, but prospective data are lacking. In the present study, we investigated the relationship between vascular complications and 21 887 longitudinal blood counts in a prospective, multicenter cohort of 776 essential thrombocythemia patients. After correction for confounding variables, no association was seen between blood counts at diagnosis and future complications. However, platelet count outside of the normal range during follow-up was associated with an immediate risk of major hemorrhage (P ‫؍‬ .0005) but not thrombosis (P ‫؍‬ .7). Elevated WBC count during follow-up was correlated with thrombosis (P ‫؍‬ .05) and major hemorrhage (P ‫؍‬ .01). These data imply that the aim of cytoreduction in essential thrombocythemia should be to keep the platelet count, and arguably the WBC count, within the normal range. This study is registered at the International Standard Randomized Controlled Trials Number Registry (www.isrctn.org) as number 72251782. (Blood. 2012;120(7):1409-1411) IntroductionThe myeloproliferative neoplasms (MPNs) comprise several chronic hematologic malignancies with overlapping clinical and molecular features. 1 Essential thrombocythemia (ET), the most prevalent of the MPNs, is characterized by increased platelet counts, increased risk of hemorrhage and thrombosis (both arterial and venous), and long-term risk of transformation to myelofibrosis or acute leukemia. Current practice aims to reduce platelet counts in ET to the normal range in high-risk patients. 2,3 However, observational studies have consistently failed to show a relationship between elevated platelet count at diagnosis or during follow-up and thrombosis risk in this disorder, 4-6 and it is therefore not clear what the target platelet count should be. Furthermore, there is evidence that leukocytosis at diagnosis is a more powerful prognostic factor for complications in ET and the related MPN, polycythemia vera. 4,5,[7][8][9] These findings have generated considerable controversy and debate about the role of blood count variables in risk stratification. 4,10 In the present study, we analyzed the relationship between blood counts and complications in the PT-1 trial, the largest multicenter randomized study performed in ET. This cohort of patients has been characterized extensively through molecular studies, 11-14 histologic analysis, 15,16 and long-term clinical followup. 17 Longitudinal blood counts have been collected over many years. MethodsThe PT-1 trial has relevant ethics and Medicines and Healthcare Products Regulatory Agency approvals in all participating countries. Patients with ET were entered into 1 of 3 PT-1 studies depending on their risk of vascular complications. High-...

First reported in 1999, germline runt-related transcription factor 1 (RUNX1) mutations are a well-established cause of familial platelet disorder with predisposition to myeloid malignancy (FPD-MM). We present the clinical phenotypes and genetic mutations detected in 10 novel RUNX1-mutated FPD-MM families. Genomic analyses on these families detected 2 partial gene deletions, 3 novel mutations, and 5 recurrent mutations as the germline RUNX1 alterations leading to FPD-MM. Combining genomic data from the families reported herein with aggregated published data sets resulted in 130 germline RUNX1 families, which allowed us to investigate whether specific germline mutation characteristics (type, location) could explain the large phenotypic heterogeneity between patients with familial platelet disorder and different HMs. Comparing the somatic mutational signatures between the available familial (n = 35) and published sporadic (n = 137) RUNX1-mutated AML patients showed enrichment for somatic mutations affecting the second RUNX1 allele and GATA2. Conversely, we observed a decreased number of somatic mutations affecting NRAS, SRSF2, and DNMT3A and the collective genes associated with CHIP and epigenetic regulation. This is the largest aggregation and analysis of germline RUNX1 mutations performed to date, providing a unique opportunity to examine the factors underlying phenotypic differences and disease progression from FPD to MM.

[(18)F]FDG PET-CT status at the end of immunochemotherapy induction in patients with FL is strongly predictive of outcome and should be considered a meaningful clinical end point in future studies.