Background/aim: Calreticulin (CALR) mutations in essential thrombocythemia (ET) are associated with younger age, higher platelet counts, and lower thrombosis rates. The present study analyzes the demographic, laboratory, and clinical features of the CALR mutation and its prognostic impact. Materials and methods: The clinical impact of CALR mutations was assessed in 391 ET patients. Results: CALR-mutation patients were more commonly male than JAK2 V617F-positive and triple-negative patients. Age at diagnosis was similar across all groups, although patients with type 2 CALR mutations were younger than those with nontype 1/nontype 2 mutations. Compared with JAK2 V617F-positive patients, CALR-mutation patients had lower leukocyte counts (9.6 × 10⁹/L vs. 10.9 × 10⁹/L), lower hemoglobin (Hb) and hematocrit (Hct) levels, higher platelet counts (1078.5 × 10⁹/L vs. 858.1 × 10⁹/L), and lower total thrombosis rates (20.8% vs. 37.8%), while the CALR-mutated and triple-negative patients had lower venous thrombosis rates than in the JAK2 V617F-positive patients. The arterial thrombosis rate before and at the time of diagnosis was lower in the CALR-mutation patients than in the JAK2 V617F-positive patients, and the total venous thrombosis rate in patients aged <60 years at the time of diagnosis was lower in the CALR-mutation and triple-negative patients than in the JAK2 V617F-positive patients. Multivariable analysis revealed cardiovascular (CV) risk to be the only independent predictor of total thrombosis. Female gender, absence of CV risk, and platelet count ≥1000 × 10⁹/L were associated with a lower incidence of arterial thrombosis. Age <60 years was associated with lower risks of arterial and venous thrombosis. Overall, thrombosis-free, and leukemia-free survival were similar across all groups, while myelofibrosis-free survival was longer in the type 2 CALR-mutation group. Conclusion: The CALR mutation was lower among females, and was associated with lower leukocyte counts, and Hb and Hct levels, and with higher platelet counts. In multivariable analysis, the apparent protective association of CALR with thrombosis was not independent.

Background/Objectives: Adolescents and young adults (AYAs) with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) constitute a distinct yet understudied population. We aimed to characterize the clinical features, treatment patterns and outcomes of AYAs with Ph-negative MPNs and to examine whether age group remains associated with thrombosis and survival after adjustment for relevant covariates. Methods: We retrospectively studied 1023 patients with Ph-negative MPNs diagnosed between 1995 and 2022 at two centers, classified as AYA (15–39 years, n = 203) or non-AYA (≥40 years, n = 820). Thrombosis and overall survival were analyzed with multivariable logistic and Cox regression adjusted for sex, MPN subtype, cardiovascular risk factors and JAK2V617F status, and transformation as cumulative incidence with death as a competing event. Results: AYA patients were more often female, more often had essential thrombocythemia, and presented with lower leukocyte counts, higher platelet counts, fewer cardiovascular risk factors (45.3% vs. 77.3%) and a lower frequency of the JAK2V617F mutation (64.0% vs. 72.7%). Arterial thrombosis was less frequent in AYAs (11.3% vs. 30.2%), whereas venous thrombosis (22.2% vs. 10.2%) and splanchnic vein thrombosis (SVT; 14.3% vs. 5.1%) were more frequent, consistently across MPN subtypes. After adjustment, AYA status remained associated with venous thrombosis (odds ratio [OR] 2.88, 95% confidence interval [CI] 1.86–4.47) and SVT (OR 3.81, 95% CI 2.17–6.70) and with lower odds of arterial thrombosis (OR 0.39, 95% CI 0.24–0.63). Cytoreductive therapy was used less often in AYAs, with a preference for interferon over hydroxyurea and ruxolitinib. The 15-year cumulative incidences of leukemic (2.0% vs. 4.9%) and myelofibrotic transformation (1.2% vs. 2.4%) did not differ significantly, although events were few. Mortality was lower (3.0% vs. 22.6%) and overall survival longer in AYAs (adjusted hazard ratio 0.11, 95% CI 0.05–0.24). Conclusions: Within the limits of a retrospective design, AYAs with Ph-negative MPNs display a venous-predominant thrombotic phenotype and favorable survival; these hypothesis-generating findings support the prospective evaluation of age-adapted risk assessment in this population.