Epidemiology, Treatment Outcomes, and Prognosis of Myelodysplastic Syndromes/Neoplasms in Taiwan: Real-World Insights and Trends.

Background: Myelodysplastic syndromes/neoplasms (MDS) are a diverse group of clonal myeloid disorders. Advances in molecular technology lead to the development of new classification systems. However, large-scale epidemiological studies on MDS in Asian countries are currently scarce.

Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame 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.

Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification.

Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R).

Validation of the prognostic significance of the 2022 European LeukemiaNet risk stratification system in intensive chemotherapy treated aged 18 to 65 years patients with de novo acute myeloid leukemia.

The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN-2022. However, validation in a large real-world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN-2022 in a cohort of 809 de novo, non-M3, younger (ages 18-65 years) AML patients receiving standard chemotherapy.

Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML.

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.

Clinico-genetic and prognostic analyses of 716 patients with primary myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia based on the 2022 International Consensus Classification.

The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which myelodysplastic syndrome (MDS) with blasts of 10%-19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS-SF3B1, and those with multi-hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal myeloid malignancies. Though several recurrent mutations are closely correlated with clinical outcomes, data concerning the association between mutation variant allele frequencies (VAF) and prognosis are limited. In this study, we performed comprehensive VAF analyses of relevant myeloid-malignancy related mutations in 698 MDS patients and correlated the results with their prognosis.

Distinct clinico-biological features in AML patients with low allelic ratio FLT3-ITD: role of allogeneic stem cell transplantation in first remission.

The mutant burden of FLT3-ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3-ITD (FLT3-ITD, AR < 0.5), clinical features, as well as genomic and transcriptomic profiles remain unclear, and evidence supporting allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains controversial.

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients.

Incorporation of long non-coding RNA expression profile in the 2017 ELN risk classification can improve prognostic prediction of acute myeloid leukemia patients.

Background: Expression of long non-coding RNAs (lncRNAs) has recently been recognized as a potential prognostic marker in acute myeloid leukemia (AML). However, it remains unclear whether incorporation of the lncRNAs expression in the 2017 European LeukemiaNet (ELN) risk classification can further improve the prognostic prediction.

Methods: We enrolled 275 newly diagnosed non-M3 AML patients and randomly assigned them to the training (n = 183) and validation cohorts (n = 92).

GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia.

Mutations of the GATA binding protein 2 (GATA2) gene in myeloid malignancies usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in different locations of GATA2 may have distinct impact on clinico-biological features and outcomes in AML patients, but little is known in this aspect. In this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and identified 44 GATA2 mutations in 43 (6.

Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor-risk factor in de novo acute myeloid leukemia patients.

Objectives: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited.

Methods: A total of 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled.

Dynamics of mutation and prognostic relevance in patients with primary myelodysplastic syndrome.

Background: gene mutation has been associated with poor prognosis in acute myeloid leukemia, but its clinical implications in myelodysplastic syndrome (MDS) and dynamic changes during disease progression remain controversial.

Results: In this study, mutation was identified in 7.9% of 469 de novo MDS patients.

Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome.

Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI).

Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS).

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited.

Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia.

Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.

Clinical and prognostic implications of Roundabout 4 (robo4) in adult patients with acute myeloid leukemia.

Background: Robo4 is involved in hematopoietic stem/progenitor cell homeostasis and essential for tumor angiogenesis. Expression of Robo4 was recently found in solid tumors and leukemia stem cells. However, the clinical implications of Robo4 expression in patients with acute myeloid leukemia (AML) remain unclear.

GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.

Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.

The N-terminal CEBPA mutant in acute myeloid leukemia impairs CXCR4 expression.

CXC chemokine receptor 4 (CXCR4) is an essential regulator for homing and maintenance of hematopoietic stem cells within the bone marrow niches. Analysis of clinical implications of bone marrow CXCR4 expression in patients with acute myeloid leukemia showed not only higher CXCR4 expression was an independent poor prognostic factor, irrespective of age, white blood cell counts, cytogenetics, and mutation status of NPM1/FLT3-ITD and CEBPA, but also showed CXCR4 expression was inversely associated with mutations of CEBPA, a gene encoding transcription factor C/EBPα. Patients with wild-type CEBPA had significantly higher CXCR4 expression than those with mutated CEBPA.

IPSS-R in 555 Taiwanese patients with primary MDS: Integration of monosomal karyotype can better risk-stratify the patients.

The revised International Prognostic Scoring System (IPSS-R) was recently developed to better assess the clinical outcome of adult patients with myelodysplastic syndrome (MDS). In this study, we aimed to investigate the prognostic impact of this new risk model on 555 MDS patients in Taiwan. Generally, the IPSS-R could discriminate MDS patients regarding risk of leukemia evolution and overall survival in our cohort and it further refined prognostic stratification in all IPSS risk categories.