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Transfusion Medicine (Oxford, England) Feb 2022Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC... (Review)
Review
Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.
Topics: Anemia; Erythrocyte Transfusion; Humans; Myelodysplastic Syndromes; Quality of Life; Transfusion Reaction
PubMed: 34927286
DOI: 10.1111/tme.12841 -
British Journal of Haematology Apr 2022
Meta-Analysis
Topics: Chelation Therapy; Humans; Iron; Iron Chelating Agents; Iron Overload; Myelodysplastic Syndromes
PubMed: 34927248
DOI: 10.1111/bjh.17998 -
Hematology (Amsterdam, Netherlands) Dec 2021Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases. Previous investigations reported that tumor necrosis factor-alpha... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases. Previous investigations reported that tumor necrosis factor-alpha (TNF-α) gene polymorphisms were associated with MDS susceptibility, but the results remained controversial. Thus, we conducted a meta-analysis to higher elucidate the correlation between gene polymorphisms and MDS susceptibility.
METHODS
The PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for eligible literatures published up to July 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association.
RESULTS
Eight studies involving 1180 MDS patients and 1387 controls were included in this meta-analysis. For the G308A polymorphism, we confirmed that the G allele (G versus A: = 0.001), GG genotypes (GG versus GA: = 0.005; GG versus GA + AA: = 0.002), and GG + AA genotypes (GG + AA versus GA: = 0.008) was significantly associated with decreased MDS susceptibility according to different genetic models. Furthermore, the G308A polymorphism was significantly correlated with decreased occurrence risk of MDS in the Caucasian population as compared with Asians in the above four genetic models ( < 0.05). However, no significant association was observed between the G238A polymorphism and MDS risk.
CONCLUSION
This research showed that G308A polymorphism might be a potential biomarker in early clinical screening of MDS, which would contribute to improving the individualized prevention of MDS patients in clinic.
Topics: Alleles; Genetic Predisposition to Disease; Humans; Myelodysplastic Syndromes; Odds Ratio; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha
PubMed: 34895100
DOI: 10.1080/16078454.2021.2009647 -
Frontiers in Oncology 2021Reduced intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported to have the same overall survival (OS) as...
Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation Is a Good Choice for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Reduced intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported to have the same overall survival (OS) as myeloablative conditioning (MAC) for patients with acute myeloid leukemia (AML) in complete remission (CR) and myelodysplastic syndrome (MDS). However, results from different studies are conflicting. Therefore, we conducted a systematic review and meta-analysis guided by PRISMA 2009 to confirm the efficacy and safety of RIC vs. MAC for AML in CR and MDS.
METHODS
We search PubMed, Web of Science, Embase, Cochrane central, clinical trial registries and related websites, major conference proceedings, and field-related journals from January 1, 1980, to July 1, 2020, for studies comparing RIC with MAC before the first allo-HSCT in patients with AML in CR or MDS. Only randomized controlled trials (RCTs) were included. OS was the primary endpoint and generic inverse variance method was used to combine hazard ratio (HR) and 95% CI.
RESULTS
We retrieved 7,770 records. Six RCTs with 1,413 participants (711 in RIC, 702 in MAC) were included. RIC had the same OS (HR = 0.95, 95% CI 0.64-1.4, = 0.80) and cumulative incidence of relapse as MAC (HR = 1.18, 95% CI 0.88-1.59, = 0.28). Furthermore, RIC significantly reduced non-relapse mortality more than total body irradiation/busulfan-based MAC (HR = 0.53, 95% CI 0.36-0.80, = 0.002) and had similar long-term OS and graft failure as MAC.
CONCLUSION
RIC conditioning regimens are recommended as an adequate option of preparative treatment before allo-HSCT for patients with AML in CR or MDS.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185436.
PubMed: 34692485
DOI: 10.3389/fonc.2021.708727 -
Transplantation and Cellular Therapy Dec 2021Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic... (Meta-Analysis)
Meta-Analysis
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation-A Systematic Review and Meta-Analysis.
BACKGROUND
Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic hematopoietic cell transplant (allo-HCT). Maintenance treatment with FLT3 inhibitors and hypomethylating agents (HMA) has been studied in various clinical trials with mixed results.
OBJECTIVE
To synthesize the current evidence on the efficacy and safety of FLT3 inhibitors and HMA for maintenance therapy after allo-HCT in AML and MDS.
METHODS
For this systematic review and meta-analysis Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to March 2021 for studies on maintenance therapies after allo-HCT in AML and MDS. Studies were excluded if they were reviews, commentaries, case series with <5 patients, or basic research articles, not published in English, not on post-allo-HCT maintenance with FLT3 inhibitors or HMA in AML or MDS, or if they were clinical trials without published results or duplicate publications from the same patient cohort. Studies with insufficient reporting of the primary endpoint (2-year overall survival [OS]) and studies using FLT3 inhibitors or HMA for pre-emptive treatment of imminent relapse based on positive measurable residual disease testing were excluded. Random-effects models were used to pool response rates for the primary outcome of 2-year OS. Hazard ratios (HR) for death and relapse were calculated for studies that included a control group. Rates of relapse-free survival (RFS), non-relapse mortality, and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Downs and Black checklist and risk of bias assessments were used to gauge the quality of individual studies. The study protocol has been registered on PROSPERO (CRD42020187298).
RESULTS
Our search strategy identified 5559 studies. Twenty-one studies with a total of 809 patients were included in the meta-analysis. The 2-year OS rates were 81.7% (95% confidence interval [CI], 73.8%-87.7%) and 65.7% (95% CI, 55.1%-74.9%) among patients treated with FLT3 inhibitors and HMA, respectively. In sensitivity analyses restricted to studies that included a control group, maintenance therapy with FLT3 inhibitors (HR for death = 0.41; 95% CI, 0.26-0.62) or HMA (HR = 0.45; 95% CI, 0.31-0.66) appeared superior to no maintenance therapy. The 2-year RFS rates were 79.8% (95% CI, 75.0%-83.9%) and 62.4% (95% CI, 50.6%-72.9%) among patients treated with FLT3 inhibitors and HMA, respectively. Rates of any grade acute and chronic GVHD were 33.1% (95% CI, 25.4%-41.8%; grade 3/4: 16.5%) and 42.5% (95% CI, 26.3%-60.4%) among FLT3 inhibitor and 42.7% (95% CI, 33.5%-52.4%; grade 3/4: 8.1%) and 41.5% (95% CI, 32.0%-51.6%) among HMA-treated patients, respectively.
CONCLUSION
Maintenance therapy with either FLT3 inhibitors or HMA after allo-HCT can lead to prolonged and improved OS and RFS with a favorable safety profile. Additional studies are needed to define the optimal duration of treatment, the role of measurable residual disease status, and transplant characteristics in patient selection.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Protein Kinase Inhibitors; fms-Like Tyrosine Kinase 3
PubMed: 34551341
DOI: 10.1016/j.jtct.2021.09.005 -
Frontiers in Pharmacology 2021The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk...
Comparison Between Decitabine and Azacitidine for Patients With Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndrome: A Systematic Review and Network Meta-Analysis.
The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected. Eight RCTs ( = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, both AZA and DAC were associated with higher overall response (OR) rate (AZA vs. CCR: relative risk (RR) = 1.48, 95% CI 1.05-2.1; DAC vs. CCR: RR = 2.14, 95% CI 1.21-3.79) and longer overall survival (OS) (AZA vs. CCR: HR = 0.64, 95% CI 0.50-0.82; DAC vs. CCR: HR = 0.84, 95% CI 0.72-0.98), and AZA showed higher rate of complete remission with incomplete blood count recovery (CRi) (HR = 2.52, 95% CI 1.27-5). For the indirect method, DAC showed a higher complete remission (CR) rate than AZA in patients with both AML (RR = 2.28, 95% CI 1.12-4.65) and MDS (RR = 7.57, 95% CI 1.26-45.54). Additionally, DAC significantly increased the risk of 3/4 grade anemia (RR = 1.61, 95% CI: 1.03-2.51), febrile neutropenia (RR = 4.03, 95% CI: 1.41-11.52), and leukopenia (RR = 3.43, 95% CI 1.64-7.16) compared with AZA. No statistical significance was found for the other studied outcomes. Compared to CCR, both AZA and DAC can promote outcomes in patients with AML and HR-MDS. DAC showed higher efficacy especially CR rate than AZA (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.
PubMed: 34483903
DOI: 10.3389/fphar.2021.701690 -
Therapeutic Advances in Hematology 2021DDX41 serves as a DNA sensor in innate immunity and mutated is pathogenic, mainly for myeloid neoplasms. (Review)
Review
BACKGROUND
DDX41 serves as a DNA sensor in innate immunity and mutated is pathogenic, mainly for myeloid neoplasms.
METHODS
In this study, "" was searched in and between 1 January 2015 and 29 April 2021 with individual-patient data seeking. A meta-analysis was not valid here due to the absence of a large dataset. Thirty articles were finally included in the qualitative analysis and 277 patients from 20 studies without overlap were involved in the quantitative summary.
RESULTS
Pooled incidence was 3.3% (95% confidence interval 2.4-4.2%) of unselected myeloid neoplasms. Patients with hematologic disorders harboring mutated were featured as 80% males, median 66 (20-88) years old at diagnosis, 75% acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 64% with normal karyotype. Eighty-five percent of patients had germline variants which were nationally diverse and more of frameshift type, whereas 64% of patients had somatic variants where p.R525H and missense dominated. and were the top frequent concomitant somatic mutations. Therapeutically, 70% overall response rate was obtained of hypomethylating agents in MDS, 96% complete remission of chemotherapy in AML, and 8% of relapse in hematopoietic stem cell transplant. Neither overall survival nor progression-free survival could be summed.
CONCLUSIONS
Several significant clinical differences were observed in different diagnosis groups, familial and sporadic cases, and p.R525H compared with other somatic variants. In conclusion, myeloid neoplasms carrying mutations were mainly older, male, MDS, and AML patients who had promising responses to treatment. Both germline and somatic variants possessed unique characteristics and groups of interest presented certain differences worth further research. (CRD42021228886).
PubMed: 34349893
DOI: 10.1177/20406207211032433 -
Leukemia Research Dec 2021
Topics: Genetic Diseases, X-Linked; Humans; Myelodysplastic Syndromes; Myeloproliferative Disorders; alpha-Thalassemia
PubMed: 34325177
DOI: 10.1016/j.leukres.2021.106670 -
Health Science Reports Sep 2021Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene... (Review)
Review
BACKGROUND AND AIMS
Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene metabolizing genes influence the outcomes of benzene exposure in the human body. This systematic review aims to elucidate the existent relationship between genetic polymorphisms and the risk of developing adverse health effects in benzene-exposed workers.
METHODS
Three databases were systematically searched until April 2020. The preferred reporting items for systematic reviews and meta-analyses method was used to select articles published between 2005 and 2020. Quality assessment and risk of bias were evaluated by the Newcastle-Ottawa scale.
RESULTS
After full-text evaluation, 36 articles remained out of 645 initially screened. The most studied health effects within the reviewed papers were chronic benzene poisoning, hematotoxicity, altered urinary biomarkers of exposure, micronucleus/chromosomal aberrations, and gene methylation. Furthermore, some polymorphisms on , , , , and , among other genes, showed a statistically significant relationship with an increased risk of developing at least one of these effects on benzene-exposed workers. However, there was no consensus among the reviewed papers on which specific polymorphisms were the ones associated with the adverse health-related outcomes, except for the rs1800566 and the null genotypes. Additionally, the smoking habit was identified as a confounder, demonstrating worse health outcomes in exposed workers that smoked.
CONCLUSION
Though there is a positive relationship between genetic polymorphisms and detrimental health outcomes for benzene-exposed workers, broader benzene-exposed cohorts that take into account the genetic diversity of the population are needed in order to determine which specific polymorphisms incur in health risks.
PubMed: 34295994
DOI: 10.1002/hsr2.327 -
Clinical Immunology (Orlando, Fla.) Aug 2021Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common...
INTRODUCTION
Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis.
MATERIALS AND METHODS
A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects.
RESULTS
Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations.
CONCLUSION
There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.
Topics: Female; GATA2 Deficiency; Granulomatous Disease, Chronic; Humans; Male; Mouth Diseases; Neutropenia; Papillon-Lefevre Disease; Phagocytes; Primary Immunodeficiency Diseases; Respiratory Burst
PubMed: 34271191
DOI: 10.1016/j.clim.2021.108796