Publications by authors named "Onyee Chan"
Article Synopsis
- The WHO and International Consensus Classification 2022 aim to improve diagnosis and treatment decisions for myelodysplastic syndromes, but disparities in their implementation exist.
- A panel of experts used a data-driven method and the Delphi consensus process to align the two classifications, focusing on genomic features to create harmonized labels for distinct clusters.
- Key findings identified nine genomic clusters, with the most significant linked to biallelic TP53 inactivation, and highlighted the inadequacy of traditional morphological assessments in capturing the complexity of these diseases.
Article Synopsis
- The study compared the outcomes of AML patients treated with a combination of hypomethylating agents and venetoclax, focusing on various levels of remission defined by ELN 2022.
- Among 120 patients, the best responses were complete remission (43.3%), partial remission (18.3%), incomplete remission (25.8%), and morphologic leukemia-free state (12.5%).
- The results indicated that those with MLFS had a history of prior myeloid malignancies and had worse overall survival and relapse-free survival compared to those who achieved better response categories.
Article Synopsis
- Mutations in the TP53 gene, especially multihit alterations, are linked to worse clinical outcomes in patients with myelodysplastic syndrome (MDS).
- This study analyzed TP53 abnormalities in 682 patients with MDS who had an isolated deletion of chromosome 5 (MDS-del(5q)), revealing that 24% had multihit mutations, indicating a greater risk for leukemic transformation.
- The study found that the effect of monoallelic mutations varies with the variant allele frequency (VAF); lower VAF (<20%) behaved like wild-type TP53, while higher VAF (≥20%) showed outcomes similar to multihit mutations, highlighting the need for careful consideration of TP53 status in
Article Synopsis
- Venetoclax-azacitidine is the standard treatment for unfit acute myeloid leukemia patients, but there is limited data on how long patients should continue therapy if they cannot tolerate it.
- In a study analyzing patients who stopped treatment due to poor tolerance, those who discontinued showed comparable outcomes to those who continued with azacitidine alone, with median overall survival of 44 months for newly diagnosed patients.
- The findings suggest that patients who stop treatment while in remission can have favorable outcomes, indicating a need for further controlled trials to explore optimal treatment durations.
Article Synopsis
- New treatment strategies are urgently needed for patients with triple-negative Myelofibrosis (TN-MF), who show poor outcomes and lack mutations in the JAK2 pathway.
- Research reveals that MYC copy number gain and elevated MYC expression are common in TN-MF, driving the disease's development through the activation of S100A9, an inflammation-related protein.
- Targeting the MYC-S100A9 pathway, either through genetic methods or small molecules, effectively improves Myelofibrosis symptoms, presenting a potential new treatment approach for this difficult-to-treat patient group.
Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch.
View Article and Find Full Text PDFBackground: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment.
Patients And Methods: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival.
Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.
J Natl Compr Canc Netw
February 2024
Article Synopsis
- - Chronic myeloid leukemia (CML) is identified by the Philadelphia chromosome, resulting from a specific genetic change between chromosomes 9 and 22, leading to a unique fusion gene (BCR::ABL1).
- - CML has three phases (chronic, accelerated, and blast), with most diagnoses occurring during the chronic phase in developed regions, and treatment mainly involves tyrosine kinase inhibitors (TKIs) to prevent progression.
- - The manuscript reviews the NCCN Guidelines for diagnosing and managing chronic phase-CML, highlighting that some patients can discontinue TKI therapy under careful supervision.
Article Synopsis
- The study focuses on the progression patterns of low-risk myelodysplastic syndrome (MDS) in a cohort of 1,914 patients, categorizing them into four distinct groups based on their disease progression.
- Key risk factors identified for progression include male gender, low blood cell counts, high bone marrow blasts, and certain genetic mutations, with specific mutations such as SRSF2 correlating with a higher risk of transformation to acute myeloid leukemia (AML).
- Notably, about 13.1% of patients with stable low-risk MDS died within two years of diagnosis, often due to complications related to cytopenia, highlighting the importance of understanding disease progression to improve treatment strategies.
Article Synopsis
- Acute myeloid leukemia (AML) outcomes are influenced by genetic factors, with NPM1 mutations found in about 30% of cases and linked to a better prognosis.
- This study involving 233 AML patients showed that those with secondary mutations (sMut) had significantly lower overall survival rates compared to those without sMut, even when considering favorable-risk AML.
- Among patients who achieved measurable residual disease negativity, those with sMut still had poorer survival compared to MRD negative patients, highlighting the adverse impact of sMut on prognosis in AML.
Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.
View Article and Find Full Text PDFNovel therapies upon failure of HMA plus venetoclax.
Hematology Am Soc Hematol Educ Program
December 2023
The efficacy and tolerability of the combination of hypomethylating agents with venetoclax (HMA-VEN) in patients with newly diagnosed acute myeloid leukemia has been a practice-changing milestone in the field. However, treatment failure and relapse remain major barriers to prolonged survival. TP53 mutation is a predictor of primary induction failure and portends especially poor outcomes.
View Article and Find Full Text PDFMyelofibrosis (MF) is commonly diagnosed in older individuals and has not been extensively studied in young patients. Given the infrequent diagnosis in young patients, analyzing this cohort may identify factors that predict for disease development/progression. We retrospectively analyzed clinical/genomic characteristics, treatments, and outcomes of patients with MF aged 18-50 years (YOUNG) at diagnosis.
View Article and Find Full Text PDFArticle Synopsis
- The swimmer plot visually represents the clinical journey of patients with core binding factor acute myeloid leukemia who received allogeneic stem cell transplants.
- It illustrates important milestones, such as treatment phases and survival times, helping to track each patient's progress over time.
- This analysis aids in understanding treatment outcomes and can guide future research and patient management strategies.
Article Synopsis
- A retrospective study evaluated the impact of next-generation sequencing (NGS) mutations on outcomes in patients with secondary acute myeloid leukemia (sAML) who were treated with CPX-351 from 2017 to 2021.
- Common mutations included DNMT3A, SRSF2, RUNX1, TET2, ASXL1, and BCOR, with a median overall survival (mOS) of 47 months for the cohort.
- While patients who cleared their mutations experienced longer mOS and relapse-free survival (RFS) numerically, the differences were not statistically significant, and alloSCT improved RFS regardless of mutational status.
Article Synopsis
- The Molecular International Prognostic Scoring System (IPSS-M) is a new model for assessing risk in patients with myelodysplastic syndromes (MDS) that incorporates genetic mutation data for better accuracy compared to previous systems like IPSS and IPSS-R.
- A large study involving 2,355 MDS patients confirmed the IPSS-M's effectiveness in predicting overall survival (OS), leukemia-free survival (LFS), and the risk of leukemic transformation.
- The model categorizes patients into six risk groups, showing significant differences in median survival times, which supports the potential of IPSS-M to enhance treatment decisions for MDS patients.
Sex Disparities in Myelodysplastic Syndromes: Genotype, Phenotype, and Outcomes.
Clin Lymphoma Myeloma Leuk
May 2023
Article Synopsis
- A study at Moffitt Cancer Center analyzed clinical and genomic data from 4580 patients with Myelodysplastic Syndromes (MDS), revealing that a majority (66%) of patients were men.
- Women with MDS were generally younger and showed different clinical features, such as lower hemoglobin levels and higher platelet counts, along with distinct genetic abnormalities and a higher incidence of therapy-related MDS compared to men.
- Despite a lower overall survival rate in men, women had better survival outcomes in lower-risk MDS cases and were more responsive to certain immunosuppressive treatments, highlighting the need for further research on the impact of biological sex in MDS.
Article Synopsis
- Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion (MLN-TK) are rare blood disorders caused by specific gene fusions, and the study investigates treatment outcomes for these conditions using tyrosine kinase inhibitors (TKIs).
- The research included 42 patients, revealing that 60% of those in chronic and blast phases responded positively to upfront TKI therapy, indicating its effectiveness.
- The findings suggest that early initiation of TKI treatment significantly enhances overall survival for patients with MLN-TK, regardless of the specific gene abnormalities involved.
Article Synopsis
- EZH2 mutations in myelodysplastic syndrome (MDS) are linked to poorer overall survival, with 4.7% of patients in a study showing these mutations.* -
- Patients with EZH2 mutations tend to be older and have lower response rates to treatments compared to those without the mutation; their median overall survival was notably worse at 30.8 months.* -
- Co-existing mutations like ASXL1 and RUNX1, along with chromosome 7 abnormalities, are associated with even poorer outcomes, highlighting the need for targeted therapies in future clinical trials.*