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Frontiers in Oncology 2020Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and...
Comparison and Implications of Mutational Profiles of Myelodysplastic Syndromes, Myeloproliferative Neoplasms, and Myelodysplastic/Myeloproliferative Neoplasms: A Meta-Analysis.
Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). However, these conditions are not exclusive, and overlap between them leads to another classification, MDS/MPN. As well as phenotype continuity, these three conditions may have genetic relationships that have not yet been identified. This study aimed to obtain their mutational profiles by meta-analysis and explore possible similarities and differences. We reviewed screening studies of gene mutations, published from January 2000 to March 2020, from PubMed and Web of Science. Fifty-three articles were eligible for the meta-analysis, and at most 9,809 cases were involved for any gene. The top mutant genes and their pooled mutation rates were as follows: (20.2% [95% CI 11.6-30.5%]) in MDS, (39.2% [95% CI 21.7-52.0%]) in MDS/MPN, and (67.9% [95% CI 64.1-71.6%]) in MPN. Subgroup analysis revealed that leukemic transformation-related genes were more commonly mutated in high-risk MDS (MDS with multilineage dysplasia and MDS with excess blasts) than that in other MDS entities. Thirteen genes including , and had significantly higher mutation frequencies in primary myelofibrosis (PMF) compared with essential thrombocythemia and polycythemia vera; this difference distinguished PMF from MPN and likened it to MDS. Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia were similar entities but showed several mutational differences. A heat map demonstrated that juvenile myelomonocytic leukemia and MDS/MPN with ring sideroblasts and thrombocytosis were two distinct entities, whereas MDS/MPN-unclassifiable was closest to high-risk MDS. Such genetic closeness or difference reflected features in the pathogenesis, diagnosis, treatment, and progression of these conditions, and could inspire future genetic studies.
PubMed: 33117717
DOI: 10.3389/fonc.2020.579221 -
The Cochrane Database of Systematic... Oct 2015Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a... (Comparative Study)
Comparative Study Review
Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders.
BACKGROUND
Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear.
OBJECTIVES
To assess the efficacy and safety of a restrictive versus liberal red blood cell transfusion strategy for patients with myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th May 2015.
SELECTION CRITERIA
RCTs including patients with long-term bone marrow failure disorders that require allogeneic blood transfusion, who are not being actively treated with a haematopoietic stem cell transplant, or intensive chemotherapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane review methodology. One author initially screened all references, and excluded any that were clearly irrelevant or duplicates. Two authors then independently screened all abstracts of articles, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant articles for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool.
MAIN RESULTS
We included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS.The quality of the evidence was very low across different outcomes according to GRADE methodology.The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above).
AUTHORS' CONCLUSIONS
This review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population.
Topics: Anemia, Aplastic; Anemia, Refractory; Bone Marrow Diseases; Clinical Protocols; Erythrocyte Transfusion; Humans; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Randomized Controlled Trials as Topic
PubMed: 26436602
DOI: 10.1002/14651858.CD011577.pub2 -
Frontiers in Oncology 2021Numerous examples in oncology have shown that better understanding the pathophysiology of a malignancy may be followed by the development of targeted treatment concepts...
Numerous examples in oncology have shown that better understanding the pathophysiology of a malignancy may be followed by the development of targeted treatment concepts with higher efficacy and lower toxicity as compared to unspecific treatment. The pathophysiology of chronic myelomonocytic leukemia (CMML) is heterogenous and complex but applying different research technologies have yielded a better and more comprehensive understanding of this disease. At the moment treatment for CMML is largely restricted to the unspecific use of cytotoxic drugs and hypomethylating agents (HMA). Numerous potential molecular targets have been recently detected by preclinical research which may ultimately lead to treatment concepts that will provide meaningful benefits for certain subgroups of patients.
PubMed: 34660314
DOI: 10.3389/fonc.2021.751668 -
Journal of Musculoskeletal & Neuronal... Mar 2021Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown.
METHODS
To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG's PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores.
RESULTS
The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma.
CONCLUSIONS
This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Neoplasms; Databases, Genetic; Gene Regulatory Networks; Humans; Immunity, Cellular; Macrophages; Osteosarcoma; Prognosis; Protein Array Analysis; Receptors, Cell Surface; Tumor Microenvironment
PubMed: 33657763
DOI: No ID Found -
Value in Health : the Journal of the... Jul 2020We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
OBJECTIVES
We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
METHODS
The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found.
RESULTS
Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia.
CONCLUSIONS
There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.
Topics: Cost-Benefit Analysis; Health Status; Hematologic Neoplasms; Humans; Models, Economic; Quality of Life; Surveys and Questionnaires
PubMed: 32762998
DOI: 10.1016/j.jval.2020.04.1825