Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The ...classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on ...their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival (P = 0.034 for older and 0.035 for younger patients) and event-free survival (P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations.
Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA
) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical ...outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA
. One hundred and thirteen CEBPA
patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPA
. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPA
patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA
, and upfront allogeneic transplantation may be indicated for better long-term disease control.
RUNX1 mutations are frequently detected in various myeloid neoplasms and implicate unfavourable clinical outcomes in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). On ...the other hand, high expression of RUNX1 is also correlated with poor prognosis in AML patients. However, the clinical relevancy of RUNX1 expression in MDS patients remains elusive. This study aimed to investigate the prognostic and biologic impacts of RUNX1 expression in MDS patients. We recruited 341 MDS patients who had sufficient bone marrow samples for next‐generation sequencing. Higher RUNX1 expression occurred more frequently in the patients with Revised International Prognostic Scoring System (IPSS‐R) higher‐risk MDS than the lower‐risk group. It was closely associated with poor‐risk cytogenetics and mutations in ASXL1, NPM1, RUNX1, SRSF2, STAG2, TET2 and TP53. Furthermore, patients with higher RUNX1 expression had significantly shorter leukaemia‐free survival (LFS) and overall survival (OS) than those with lower expression. Subgroups analysis revealed that higher‐RUNX1 group consistently had shorter LFS and OS than the lower‐RUNX1 group, no matter RUNX1 was mutated or not. The same findings were observed in IPSS‐R subgroups. In multivariable analysis, higher RUNX1 expression appeared as an independent adverse risk factor for survival. The prognostic significance of RUNX1 expression was validated in two external public cohorts, GSE 114922 and GSE15061. In summary, we present the characteristics and prognosis of MDS patients with various RUNX1 expressions and propose that RUNX1 expression complement RUNX1 mutation in MDS prognostication, wherein patients with wild RUNX1 but high expression may need more proactive treatment.
Primary pulmonary lymphoma is an uncommon disease, and extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT) is the most common type of pulmonary lymphoma. The most frequent ...pattern observed in chest computed tomography (CT) is consolidation, followed by nodules and mass. The differentiation of pulmonary MALT lymphoma from other lung diseases is critical for disease management and treatment. However, pulmonary MALT lymphoma with isolated endobronchial manifestation has seldomly been reported. Here, we report a case of an elderly woman who presented with a four‐month history of cough, dyspnoea, and haemoptysis. Chest CT scan revealed left main bronchus narrowing without lung parenchymal lesion. Bronchoscopic examination was performed, and the diagnosis of primary pulmonary MALT lymphoma with isolated endobronchial involvement was made. She has been successfully treated with rituximab.
We describe a case of primary pulmonary mucosa‐associated lymphoid tissue (MALT) lymphoma presented as an endobronchial tumor without lung parenchymal involvement.
During the COVID-19 pandemic, physical inactivity and sedentary behaviors (i.e., longer sitting time and excessive gaming) increased because governments across the globe adopted stringent mitigation ...strategies such as social distancing and lockdowns to curb the spread of the virus. Excessive gaming was one of the coping mechanisms used to deal with the pressure associated with the pandemic. Moreover, perceived weight stigma (PWS) and weight status became more salient concerns among young adults during the COVID-19 pandemic. The current study sought to investigate the relationship between time spent sitting, excessive gaming, weight status, and PWS of Taiwanese Young adults. Additionally, weight status and PWS were examined as mediators between both sedentary behaviors.
This cross-sectional study involved 600 participants who were recruited through Taiwan universities. All participants completed a demographic questionnaire (including weight and height) and self-report measures including the International Physical Activity Questionnaire short form (IPAQ-SF), the Perceived Weight Stigma Scale (PWSS), and the Internet Gaming Disorder Scale-short form (IGDS9-SF). PROCESS model was performed to test the potential mediation roles of weight status and PWS. Moreover, we categorized participants into two groups based on the sitting-time item in the IPAQ-SF: students whose sitting time was less than 8 h daily, and those more than 8 h daily.
The group that had less than 8 h had significantly higher PWS and IGDS9-SF scores than the other group. Sitting time was negatively associated with weight status, PWS, and IGDS9-SF. Additionally, we found a significantly direct effect between time spent sitting and excessive gaming. Both weight status and PWS were significant mediators in the association between time spent sitting and excessive gaming.
Conclusions: The present study demonstrated important negative correlates of excessive sedentary behaviors. Prevention efforts should focus on promoting physical activity and providing information to decrease sedentary behavior among university students.
In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization ...(WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification.
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