Objective: We investigated the occurrence and characteristics of secondary solid cancers (SSCs) in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) from T & uuml;rkiye. We identified the potential risk factors for SSC development, including the impact of cytoreductive therapies, and we assessed the influence of SSC on patient survival. Materials and Methods: A total of 1013 PhMPN patients diagnosed between 1995 and 2022 were retrospectively analyzed. Data related to demographics, clinical and laboratory parameters, SSC development, cytoreductive therapy exposure, and survival outcomes were collected. Statistical analyses were performed using IBM SPSS Statistics 26.0. Results: Of the analyzed PhMPN patients, 6.6% developed SSC, with carcinoma being the most common type. Older age at the time of PhMPN diagnosis and male sex were associated with SSC occurrence. PhMPN patients diagnosed with SSC and patients with no diagnosis of SSC showed no significant difference in complete blood count results, spleen size, PhMPN diagnostic groups, or driver mutation frequencies. However, patients with SSC had a higher frequency of arterial thrombosis and a tendency towards an increased rate of total thrombosis (p=0.030 and p=0.069, respectively). In multivariate analysis, arterial thrombosis was the sole independent risk factor and interferon (IFN)-based therapy was the sole protective factor for SSC development. Median overall survival (OS) did not differ between patients with and without SSC except for polycythemia vera patients with SSC, who had shorter OS (175 +/- 15 versus 321 +/- 26 months, respectively; p=0.005). Conclusion: This study highlights the prevalence and characteristics of SSCs in Turkish patients diagnosed with PhMPNs. Arterial thrombosis was associated with increased SSC risk while IFN-based therapy offered potential protection from SSC. Screening for SSC in Ph- MPN patients with arterial thrombosis may be valuable. These findings emphasize the importance of malignancy screening in Ph- MPN patients, especially in high-risk subgroups, and call for further research to elucidate the underlying mechanisms and optimize treatment strategies.

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.