115 research outputs found
2-Maximal Submodules and Related Concepts.
"Throughout this paper R represents commutative ring with identity and M is unitary left R-module", the purpose of this paper is to study new concept (up to our knowledge) , named 2-maximal submodule which is a generalization of maximal submodule , "where a submodule N of an R-module M is called 2-maximal" submodul of M if and only if M/N is 2-regular R-module . Many characterizations and properties of 2-maximal submodules are given . Moreover we studied the behavior of 2-maximal submodule in some classes of module . Finally we give the sufficient condition 2-maximal submodules to be semi-maximal weak-maximal submodules are introduced
Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia Patients Treated With Hypomethylating Agents
Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2mut/ASXL1wt genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNX1mut (Hazard Ratio [HR] = 2.00, p = .011), CBLmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log10(WBC) HR = 2.30, p = .005) independently predicted worse OS while the TET2mut/ASXL1wt predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores CPSS and GFM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX1 mutations. Keywords: Chronic myelomonocytic leukemia, Hypomethylating agents, Somatic mutations, Prognosi
Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study
Toward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS)
Notable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging availability of oral MDS therapies holds the promise of improving patients' health‐related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient‐reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease. We provide practical considerations to support investigators in generating high‐quality PRO data in future MDS trials. We first describe several challenges that are to be thoughtfully considered when designing an MDS‐focused clinical trial with a PRO endpoint. We then discuss aspects related to the design of the study, including PRO assessment strategies. We also discuss statistical approaches illustrating the potential value of time‐to‐event analyses and their implications within the estimand framework. Finally, based on a literature review of MDS randomized controlled trials with a PRO endpoint, we note the PRO items that deserve special attention when reporting future MDS trial results. We hope these practical considerations will facilitate the generation of rigorous PRO data that can robustly inform MDS patient care and support treatment decision‐making for this patient population
Clinical and genomic-based decision support system to define the optimal timing of allogeneic hematopoietic stem-cell transplantation in patients with myelodysplastic syndromes
Statistical Scienc
An Agenda to Advance Research in Myelodysplastic Syndromes: A TOP 10 Priority List From the First International Workshop in MDS
Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes
Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response
Increased release of the N-terminal and C-terminal portions of the prohormone of atrial natriuretic factor during immersion-induced central hypervolemia in normal humans (42990)
AML-399 A phase 2, open-label, multiarm, multicenter study to evaluate magrolimab combined with antileukemia therapies for first-line, relapsed/refractory, or maintenance treatment of acute myeloid leukemia (AML)
AML-399 A phase 2, open-label, multiarm, multicenter study to evaluate magrolimab combined with antileukemia therapies for first-line, relapsed/refractory, or maintenance treatment of acute myeloid leukemia (AML)
- …