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IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

Background: Genomic sequencing technologies have identified isocitrate dehydrogenase (IDH) mutations in haematological malignancies. The prognostic implications of somaticIDH mutation (mIDH) in myelodysplastic syndromes (MDS) remain controversial.Methods: Mutations inIDH1 andIDH2were detected using genomic sequencing technologies in 97 patients with MDS.Results: Seven (7.2%) mutations were identified: 3 inIDH1 (all R132C) and 4 inIDH2 (3 R140Q and 1 R140L). The frequency of mutation was 16.6% (2/12) in refractory anaemia with excess blasts (RAEB)-1 and 14.7% (5/34) in RAEB-2.IDH1/2 mutations were closely associated with higher bone marrow blast counts (median 10.0 vs. 2.3%;p = 0.019) and lower absolute neutrophil counts (median 0.44 × 109/L vs. 1.21 × 109/L; p = 0.027). AllIDH mutations were mutually exclusive and heterozygous.IDH mutations were not significantly correlated with any specific karyotype. Patients withIDH1 mutations exhibited shorter overall and progression-free survival (OS and PFS;p = 0.039 andp = 0.042, respectively), whereasIDH2 mutations did not affect OS or PFS (p = 0.560 andp = 0.218, respectively). Multivariate analysis indicated thatIDH1 mutation (p = 0.018; hazard ratio [HR] 4.735; 95% confidence interval [CI] 1.299-17.264), karyotype risk (p = 0.036; HR 1.619; 95% CI 1.033-2.539) and the revised International Prognostic Scoring System risk category (p
Source: Acta Haematologica - Category: Hematology Source Type: research

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Conclusion.Azacitidine effects in these patients, most with non‐del(5q) LR‐MDS, were promising and generally similar to those reported for lenalidomide in similar patients. The choice of initial therapy is important because most patients eventually stop responding to front‐line therapy and alternatives are limited.Implications for Practice.Lower‐risk myelodysplastic syndromes (LR‐MDS) are primarily characterized by anemia. After erythropoiesis‐stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients. This meta‐analysis of 233 azacitidi...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Leukemias, Academia-Pharma Intersect, Hematologic Malignancies ‐ Pharma Intersect: Hematologic Malignancies Source Type: research
SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), cha...
Source: Journal of Hematology and Oncology - Category: Hematology Authors: Tags: Research Source Type: research
We report the extraordinary case of a patient with MDS who developed T‐LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite‐like papules and intractable pruritus.
Source: Clinical And Experimental Dermatology - Category: Dermatology Authors: Tags: Concise Report Source Type: research
AbstractMyelodysplastic syndromes (MDS) are heterogeneous clonal disorders ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukaemia. Comorbid conditions have rarely been systematically studied among patients with MDS. Older age per se has a negative impact on survival of MDS patients, in particular of those with lower risk. However, age indirectly affects also the survival of higher-risk patients by limiting their eligibility to intensive treatments. In addition, ageing is associated with an increasingly high risk of developing comorbidity, and a high prevalence of co...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre–mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings. Srsf2-mutated hematopoiet...
Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research
Background: Studies of bone marrow cell clonal alterations in patients with Fanconi anemia (FA), a cancer-prone inherited bone marrow failure (BMF) syndrome, have focused on their role in progression from BMF to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The role of such alterations on patient outcomes after hematopoietic cell transplantation (HCT) is unknown.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
CPX-351 is a dual-drug liposomal encapsulation of cytarabine (C) and daunorubicin (D) that delivers a synergistic 5:1 drug ratio and is FDA-approved for adults with newly diagnosed therapy-related AML or AML with MDS-related changes. In a randomized, phase 3 study (NCT01696084) in patients (pts) 60-75 y with newly diagnosed sAML, CPX-351 significantly improved overall survival (OS) and remission rates vs 7  + 3. RAEB-t AML, often defined as bone marrow blasts 20%-29%, shares many features with myelodysplastic syndrome (MDS).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Anemia is quite frequently diagnosed in older individuals and is a key indicator of various reactive and clonal conditions. Many underlying diseases, like myelodysplastic syndrome (MDS), develop preferentially in elderly individuals. The prevalence of anemia at older age is increasing, and this is mainly attributable to more frequently applied diagnostics and demographic changes in our societies. The etiology of anemia at older age is complex and ranges from bone marrow failure syndromes to chronic kidney disease, and from nutritional deficiencies to inflammatory processes including inflammaging in immunosenescence. In a s...
Source: Blood - Category: Hematology Authors: Tags: Free Research Articles, Red Cells, Iron, and Erythropoiesis, Review Articles, Review Series, Clinical Trials and Observations Source Type: research
Conclusion Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
Abstract Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through "trapping" the PARP enzyme on damaged DNA. Phase I and III studies have demonstrated activity an...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
More News: Anemia | Cancer & Oncology | Hematology | Myelodysplastic Syndrome