GSE225352 Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: Clinical efficacy and correlative analyses
Contributors : Marina Konopleva ; Natalia BaranSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMalignancies can become reliant on glutamine as an alternative energy source and as a facilitator of aberrant DNA methylation, thus implicating glutaminase (GLS) as a potential therapeutic target. We demonstrate preclinical synergy of telaglenastat (CB-839), a selective GLS inhibitor, when combined with azacytidine (AZA), in vitro and in vivo, followed by a phase Ib/II study of the combination in patients with advanced MDS. Treatment with telaglenastat/AZA led to an ORR of 70% with CR/mCRs...
Source: GEO: Gene Expression Omnibus - February 12, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Azacitidine induced lung injury: report and contemporary discussion on diagnosis and management
Azacitidine, a hypomethylating agent, has caused a paradigm shift in the outcomes of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who are not eligible for stem cell transplantation, particularly in combination with BCL2 and IDH inhibitors. Azacitidine and Azacitidine-based combinations have been widely considered a safe low-intensity therapy when compared to traditional conventional treatments. The development of lung toxicity from azacitidine is not a well-characterized adverse event. However, if it happens, it can be fatal, especially if not recognized and treated promptly. In this review...
Source: Frontiers in Oncology - February 9, 2024 Category: Cancer & Oncology Source Type: research
The clinical outcomes of haploidentical stem cell transplantation (haplo-HSCT) for patients with therapy-related myelodysplastic syndrome: comparable to de novo myelodysplastic syndrome
This study aimed to estimate and compare the clinical outcomes of haploidentical stem cell transplantation (haplo-HSCT) for t-MDS and de novo MDS. We retrospectively analyzed 96 patients with MDS who received haplo-HSCT between January 2015 and December 2021. Eleven patients with t-MDS and 85 patients with de novo MDS were matched using the case-pair method in a 1:8 ratio with the following pairing criteria: (1) sex, (2) age ( ± 5 years), (3) year of haplo-HSCT (± 2 years), and (4) blast cell counts (≥ 5% or not). The 3-year overall survival and disease-free survival after haplo-HSCT for t-MDS versus de novo MD...
Source: Clinical and Experimental Medicine - February 8, 2024 Category: Research Source Type: research
Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE
CONCLUSION: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients.PMID:38323704 | DOI:10.1111/trf.17721 (Source: Transfusion)
Source: Transfusion - February 7, 2024 Category: Hematology Authors: Rena Buckstein Jeannie Callum Anca Prica David Bowen Richard A Wells Brian Leber Nancy Heddle Lisa Chodirker Matthew Cheung Lee Mozessohn Karen Yee Jennifer Gallagher Anne Parmentier Erin Jamula Liying Zhang Alex Mamedov Simon J Stanworth Yulia Lin Source Type: research
Cancers, Vol. 16, Pages 705: Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature
We describe eight cases of atypical NPM1mut-MNs from our institution and review the literature. We include a rare case of concurrent prostate carcinoma and MN consistent with chronic eosinophilic leukemia, progressing to myeloid sarcoma of the skin. Of the remaining seven cases, five were CMML and two were MDS. NPM1 mutations occur in 3–5% of CMML and 1–6% of MDS, with an increased likelihood of rapid evolution to AML. Their influence on disease progression varies, and their prognostic significance in non-acute MNs is less established than in AML. Non-acute MNs with NPM1 mutations may display an...
Source: Cancers - February 7, 2024 Category: Cancer & Oncology Authors: Sandra Casta ño-Díez Francesca Guijarro M ònica López-Guerra Amanda Isabel P érez-Valencia Marta G ómez-Núñez Dolors Colomer Marina D íaz-Beyá Jordi Esteve Mar ía Rozman Tags: Review Source Type: research
Decitabine-containing conditioning improved outcomes for children with higher-risk myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation
This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS...
Source: Annals of Hematology - February 6, 2024 Category: Hematology Source Type: research
Comparison of melphalan dose in patients with myelodysplastic syndrome undergoing allogeneic transplantation with reduced-intensity conditioning
The utilization of allogenic hematopoietic stem cell transplantation (allo-HSCT) as a therapeutic intervention for myelodysplastic syndrome (MDS) presents the potential for curative outcomes. However, allo-HSCT also incurs non-relapse mortality (NRM) due to complications such as graft-versus-host disease (GVHD), severe infections, and regimen-related toxicities1-3. Initially, allo-HSCT was restricted to younger patients who were appropriate for myeloablative conditioning (MAC)4-6. However, the advent of reduced-intensity conditioning (RIC) has expanded the pool of eligible elderly patients for allo-HSCT7-9. (Source: Biolog...
Source: Biology of Blood and Marrow Transplantation - February 6, 2024 Category: Hematology Authors: Shuhei Kurosawa, Yoshimitsu Shimomura, Hidehiro Itonaga, Yuta Katayama, Makoto Onizuka, Masatsugu Tanaka, Hikaru Kobayashi, Yukiyasu Ozawa, Masashi Sawa, Junya Kanda, Noriko Doki, Shin Fujisawa, Naoyuki Uchida, Takahiro Fukuda, Yoshiko Atsuta, Ken Ishiyam Source Type: research
Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome: A prospective multicenter clinical cohort study
Chin Med J (Engl). 2024 Feb 2. doi: 10.1097/CM9.0000000000002963. Online ahead of print.NO ABSTRACTPMID:38310445 | DOI:10.1097/CM9.0000000000002963 (Source: Chinese Medical Journal)
Source: Chinese Medical Journal - February 4, 2024 Category: General Medicine Authors: Yigeng Cao Mingyang Wang Fuxu Wang Wenwen Guo Yueshen Ma Xiaoyun Li Yi He Aiming Pang Rongli Zhang Weihua Zhai Xin Chen Qiaoling Ma Jialin Wei Donglin Yang Yong Huang Dan Feng Jia Liu Xin Gao Shupeng Wen Wen Wang Tao Wang Ying Li Xiaosheng Fang Yingchun L Source Type: research
Aplastic anemia: history and recent developments in diagnosis and treatment
Int J Hematol. 2024 Feb 4. doi: 10.1007/s12185-024-03715-1. Online ahead of print.ABSTRACTAcquired aplastic anemia is an immune-mediated disease that targets hematopoietic stem cells, which is diagnosed by findings of peripheral blood pancytopenia and hypocellular bone marrow. Although the diagnostic definition is simple, differential diagnosis from other overlapping hematopoietic disorders such as hypoplastic myelodysplastic syndrome and inherited bone marrow failure syndrome is not easy. Immune suppressive therapy and allogeneic hematopoietic stem cell transplantation are important treatment approaches for aplastic anemi...
Source: International Journal of Hematology - February 3, 2024 Category: Hematology Authors: Yasushi Onishi Source Type: research
PARP inhibitor maintenance treatment for newly diagnosed ovarian cancer patients: a real-world study from China
ConclusionFocusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - February 2, 2024 Category: Cancer & Oncology Source Type: research
The clinical characteristics, gene mutations and outcomes of myelodysplastic syndromes with diabetes mellitus
ConclusionsMDS patients with DM have an inferior prognosis which may due to higher infection incidence, withTET2 andSF3B1 mutations being more frequent in those cases. (Source: Journal of Cancer Research and Clinical Oncology)
Source: Journal of Cancer Research and Clinical Oncology - February 2, 2024 Category: Cancer & Oncology Source Type: research
Azacitidine Post-transplant Maintenance Improves Disease Progression in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
For patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic transplantation (alloHCT), disease relapse remains the most common reason for transplant failure and patient death1. It has been shown that immune evasion with the emerging selection of subclones resistant to graft versus leukemia effect is one of the most common mechanisms underlying post-transplant relapse. Eloquently designed studies showed that it was not the acquisition of previously unknown disease specific mutations that was leading to the relapse after alloHCT but the downregulation of major histoco...
Source: Clinical Lymphoma, Myeloma and Leukemia - February 2, 2024 Category: Hematology Authors: Oren Pasvolsky, Rima M. Saliba, Uday R. Popat, Amin Alousi, Rohtesh Mehta, Jason Yeh, Gheath Al-Atrash, Masood Adeel, Jeremy Ramdial, David Marin, Gabriela Rondon, Partow Kebriaei, Richard Champlin, Naval Daver, Courtney Dinardo, Nicholas J. Short, Elizab Tags: Original Study Source Type: research
Patterns of lower risk myelodysplastic syndrome progression: factors predicting progression to high-risk myelodysplastic syndrome and acute myeloid leukemia
Haematologica. 2024 Feb 1. doi: 10.3324/haematol.2023.283661. Online ahead of print.ABSTRACTThe patterns of low risk myelodysplastic syndrome (MDS) progression, and the clinical and molecular features of those patterns are not well described. We divided our low risk (LR) MDS patients (n=1914) into 4 cohorts: 1) Patients who remained LR-MDS (LR-LR; n=1300; 68%), 2) Patients who progressed from LR to HR MDS (LR-HR) without AML transformation (n=317; 16.5%), 3) Patients who progressed from LR to HR MDS and then AML (LR-HR-AML; n=124; 6.5%), 4) Patients who progressed from LR MDS to AML directly (LR-AML; n=173; 9%). Risk facto...
Source: Haematologica - February 1, 2024 Category: Hematology Authors: Akriti G Jain Somedeb Ball Luis Aguirre Najla Al Ali David Kaldas Sara Tinsley-Vance Andrew Kuykendall Onyee Chan Kendra Sweet Jeffrey E Lancet Eric Padron David A Sallman Rami Komrokji Source Type: research
Genetic landscape and clinical outcomes of patients with BCOR mutated myeloid neoplasms
Haematologica. 2024 Feb 1. doi: 10.3324/haematol.2023.284185. Online ahead of print.ABSTRACTThe BCL6-corepressor (BCOR) is a tumor-suppressor gene located on the short arm of chromosome X. Data is limited regarding factors predicting survival in BCOR-mutated (mBCOR) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We evaluated 138 patients with mBCOR myeloid disorders, of which 36 (26.1%) had AML and 63 (45.6%) had MDS. Sixty-six (47.8%) patients had a normal karyotype while 18 (13%) patients had complex karyotype. BCOR-mutated MDS/AML were highly associated with RUNX1 and U2AF1 comutations. In contrast, TP...
Source: Haematologica - February 1, 2024 Category: Hematology Authors: Anmol Baranwal Mark Gurney Rami Basmaci Bahga Katamesh Rong He David S Viswanatha Patricia Greipp James Foran Talha Badar Hemant Murthy Cecilia Arana Yi Jeanne Palmer Abhishek A Mangaonkar Mrinal M Patnaik Mark R Litzow William J Hogan Kebede Begna Naseem Source Type: research
