Summary The aim of this study was to compare the genomic features and clinical outcomes between paediatric and young adult patients (PAYA, <40 years) and older adults (OA, ≥40 years) with myeloproliferative neoplasms (MPN) to gain insight into pathogenesis, disease prognosis and management. Of 630 MPN patients, 171 (27%) were PAYA with an average age at diagnosis of 31 years. Females were more prevalent in PAYA than OA (71% vs 58%; p = 0.002), and PAYA more frequently presented with essential thrombocytosis (ET) at diagnosis (67% vs 39%; p < 0.001). The presence of a JAK2 somatic mutation was higher in OA (80.4% vs 64.3%; p < 0.001), while a CALR mutation or lack of any traditional driver mutation was more common in PAYA (20.5% vs 10.5%; p = 0.001, 8.8% vs 3.7%; p = 0.01 respectively). Venous thrombosis was more common in PAYA compared to OA (19.8% vs 10.7%; p = 0.002). PAYA had a higher prevalence of familial MPN and familial cancer predisposition, and two PAYA patients harboured pathogenic germline JAK2 lesions. PAYA demonstrated longer survival from diagnosis than OA (median not reached vs 13 years), while disease transformation was less frequent (19.3% vs 37.9%).

No abstract

Immune TTP (iTTP) survivors have increased risk of cardiovascular disease including stroke, and report persistent cognitive difficulties during remission. We conducted this prospective study of iTTP survivors in clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neuro-deficits, during clinical remission. We also tested the hypothesis that SCI is associated with cognitive impairment assessed using the NIH ToolBox cognition battery. We used fully corrected T scores adjusted for age, sex, race, and education. Based on DSM-5 criteria, we defined mild and major cognitive impairment as T-scores that are 1-2 SD and &gt; 2 SD below the mean on at least one test, respectively. Forty-two patients have been enrolled, with 36 completing MRI.SCI was present in 50% (18) , of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs. 27.7%, P=0.026) including major cognitive impairment (50% vs. 5.6%, P=0.010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment [OR 10.5 (95% CI 1.45 - 76.63); P = 0.020] and major cognitive impairment [OR 7.98 (95% CI 1.11 - 57.27); P = 0.039] after adjusting for history of stroke and Beck depression inventory scores. In summary, MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these 'silent' infarcts are neither silent nor innocuous.