-
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 -
Critical Reviews in Oncology/hematology Apr 2024We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.
Topics: Humans; Prospective Studies; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Progression-Free Survival; Transplantation Conditioning; Tumor Suppressor Protein p53
PubMed: 38423375
DOI: 10.1016/j.critrevonc.2024.104310 -
Journal of the American Academy of... Jun 2024
Review
PubMed: 38906261
DOI: 10.1016/j.jaad.2024.05.086 -
The Cochrane Database of Systematic... Oct 2014The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive... (Review)
Review
BACKGROUND
The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit.
OBJECTIVES
To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS).
SEARCH METHODS
We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule.
DATA COLLECTION AND ANALYSIS
We did not identify any trials eligible for inclusion in this review.
MAIN RESULTS
No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment.
AUTHORS' CONCLUSIONS
We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and in insufficient detail) comparing deferasirox with deferoxamine, placebo or no treatment and data will hopefully be available soon. These results will be important to inform physicians and patients on the advantages and disadvantages of this treatment option.
Topics: Benzoates; Chelation Therapy; Deferasirox; Humans; Iron Chelating Agents; Iron Overload; Myelodysplastic Syndromes; Triazoles
PubMed: 25348770
DOI: 10.1002/14651858.CD007461.pub3 -
Blood Advances Jun 2023Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because...
Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because of the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL and nadir of 5.5 g/dL. The most common direct antiglobulin test (DAT) result was the presence of complement and absence of immunoglobulin G (IgG) bound to red blood cells, although other findings were observed in one-third of cases. DL antibody class and specificity were reported for 71 patients, of which 83.1% were IgG anti-P. The use of corticosteroids is common, although we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Among patients with follow-up, 99% (213 of 216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered that contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.
Topics: Child; Humans; Hemoglobinuria, Paroxysmal; Erythrocytes; Anemia, Hemolytic, Autoimmune; Adrenal Cortex Hormones; Immunoglobulin G
PubMed: 36716137
DOI: 10.1182/bloodadvances.2022009516 -
Journal of Clinical Medicine Sep 2019Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML)... (Review)
Review
Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1-76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7-145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9-70.2%) and 40.2% (95% CI, 28.0-53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1-64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3-32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4-53.9%). Approximately 29% of the patients suffered from grades 2-4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1-19.8%) and 21.1% (95% CI, 18.8-23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.
PubMed: 31514339
DOI: 10.3390/jcm8091437 -
Journal of Clinical Immunology Jan 2023Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We... (Review)
Review
BACKGROUND AND PURPOSE
Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We performed a systematic review of the available clinical and therapeutics aspects of the SIFD syndrome.
METHODS
A systematic review according to PRISMA approach, including all articles published before the 30 of July 2021 in Pubmed and EMBASE database, was performed.
RESULTS
The search identified 29 publications describing 58 unique patients. To date, 41 unique mutations have been reported. Onset of disease is very early with a median age of 4 months (range 0-252 months). The most frequent manifestations are haematologic such as microcytic anaemia or sideroblastic anaemia (55/58), recurrent fever (52/58), neurologic abnormalities (48/58), immunologic abnormalities in particular a humoral immunodeficiency (48/58), gastrointestinal signs and symptoms (38/58), eye diseases as cataract and retinitis pigmentosa (27/58), failure to thrive (26/58), mucocutaneous involvement (29/58), sensorineural deafness (19/58) and others. To date, 19 patients (35.85%) died because of disease course (16) and complications of hematopoietic cell stems transplantation (3). The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) is dramatically changing the natural history of this disease.
CONCLUSIONS
SIFD syndrome is a novel entity to consider in a child presenting with recurrent fever, anaemia, B-cell immunodeficiency and neurodevelopmental delay. To date, therapeutic guidelines are lacking but anti-TNFα treatment and/or HCST are attractive and might modify the clinical course of this syndrome.
Topics: Child; Humans; Anemia, Sideroblastic; Immunologic Deficiency Syndromes; Fever; Mutation; Developmental Disabilities
PubMed: 35984545
DOI: 10.1007/s10875-022-01343-0 -
Disease Markers 2018Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in various diseases. However, whether ANG can serve as a diagnostic or prognostic marker for different diseases remains a matter of debate.
METHODS
Here, we performed a systematic review and meta-analysis of the literature utilizing PubMed, Web of Science, and Scopus search engines to identify all publications comparing plasma or serum ANG levels between patients with different diseases and healthy controls, as were studies evaluating circulating ANG levels in healthy populations, pregnant women, or other demographic populations.
RESULTS
This study demonstrated that the serum ANG concentration in healthy populations was 336.14 ± 142.83 ng/ml and remained relatively stable in different populations and regions. We noted no significant differences in serum ANG levels between patients and healthy controls, except in cases in which patients suffered from cancer or cardiovascular diseases. The serum ANG concentrations were significantly higher in patients who developed colorectal cancer, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, and heart failure than those in healthy controls.
CONCLUSION
ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases.
Topics: Angiotensins; Biomarkers; Case-Control Studies; Colorectal Neoplasms; Female; Heart Failure; Humans; Leukemia, Myeloid; Male; Multiple Myeloma; Myelodysplastic Syndromes
PubMed: 29736193
DOI: 10.1155/2018/1984718 -
Frontiers in Oncology 2020Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and...
BACKGROUND AND AIM
Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.
METHODS
A full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.
RESULTS
This meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47-0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36-0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41-0.83, P = 0.003) and 0.6 (95% CI: 0.37-0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45-0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.
CONCLUSIONS
Thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.
PubMed: 33324559
DOI: 10.3389/fonc.2020.582686 -
The Cochrane Database of Systematic... Sep 2017Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects. Thrombopoietin (TPO) mimetics represent an alternative treatment option for MDS patients with thrombocytopenia. However, it remains unclear, whether TPO mimetics influence the increase of blast cells and therefore to premature progression to AML.
OBJECTIVES
To evaluate the efficacy and safety of thrombopoietin (TPO) mimetics for patients with MDS.
SEARCH METHODS
We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 2000 to August 2017), trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion.
SELECTION CRITERIA
We included randomised controlled trials comparing TPO mimetics with placebo, no further treatment or another TPO mimetic in patients with MDS of all risk groups, without gender, age or ethnicity restrictions. Additional chemotherapeutic treatment had to be equal in both arms.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials, disagreements were resolved by discussion. Risk ratio (RR) was used to analyse mortality during study, transformation to AML, incidence of bleeding events, transfusion requirement, all adverse events, adverse events >= grade 3, serious adverse events and platelet response. Overall survival (OS) and progression-free survival (PFS) have been extracted as hazard ratios, but could not be pooled as results were reported in heterogenous ways. Health-related quality of life and duration of thrombocytopenia would have been analysed as standardised mean differences, but no trial reported these outcomes.
MAIN RESULTS
We did not identify any trial comparing one TPO mimetic versus another. We analysed six eligible trials involving 746 adult patients. All trials were reported as randomised and double-blind trials including male and female patients. Two trials compared TPO mimetics (romiplostim or eltrombopag) with placebo, one trial evaluated eltrombopag in addition to the hypomethylating agent azacitidine, two trials analysed romiplostim additionally to a hypomethylating agent (azacitidine or decitabine) and one trial evaluated romiplostim in addition to the immunomodulatory drug lenalidomide. There are more data on romiplostim (four included, completed, full-text trials) than on eltrombopag (two trials included: one full-text publication, one abstract publication). Due to small sample sizes and imbalances in baseline characteristics in three trials and premature termination of two studies, we judged the potential risk of bias of all included trials as high.Due to heterogenous reporting, we were not able to pool data for OS. Instead of that, we analysed mortality during study. There is little or no evidence for a difference in mortality during study for thrombopoietin mimetics compared to placebo (RR 0.97, 95% confidence interval (CI) 0.73 to 1.27, N = 6 trials, 746 patients, low-quality evidence). It is unclear whether the use of TPO mimetics induces an acceleration of transformation to AML (RR 1.02, 95% CI 0.59 to 1.77, N = 5 trials, 372 patients, very low-quality evidence).Thrombopoietin mimetics probably improve the incidence of all bleeding events (RR 0.92, 95% CI 0.86 to 0.99, N = 5 trials, 390 patients, moderate-quality evidence). This means that in the study population, 713 out of 1000 in the placebo arm will have a bleeding event, compared to 656 of 1000 (95% CI 613 to 699) in the TPO mimetics arm. There is little or no evidence for a difference that TPO mimetics significantly diminish the rate of transfusion requirement (RR 0.83, 95% CI 0.66 to 1.05, N = 4 trials, 358 patients, low-quality evidence). No studies were found that looked at quality of life or duration of thrombocytopenia.There is no evidence that patients given TPO mimetics suffer more all adverse events (RR 1.01, 95% CI 0.96 to 1.07, N = 5 trials, 390 patients, moderate-quality evidence). There is uncertainty whether the number of serious adverse events decrease under therapy with TPO mimetics (RR 0.89, 95% CI 0.54 to 1.46, N = 4 trials, 356 patients, very low-quality evidence).We identified one ongoing study and one study marked as completed (March 2015), but without publication of results for MDS patients (only results reported for AML and MDS patients together). Both studies evaluate MDS patients receiving eltrombopag in comparison to placebo.
AUTHORS' CONCLUSIONS
No trial evaluated one TPO mimetic versus another.Six trials including adult patients analysed one TPO mimetic versus placebo, sometimes combined with standard therapy in both arms. Given the uncertainty of the quality of evidence, meta-analyses show that there is little or no evidence for a difference in mortality during study and premature progress to AML. However, these assumptions have to be further explored. Treatment with TPO mimetics resulted in a lower number of MDS patients suffering from bleeding events.There is no evidence for a difference between study groups regarding transfusion requirement. Enlarged sample sizes and a longer follow-up of future trials should improve the estimate of safety and efficacy of TPO mimetics, moreover health-related quality of life should be evaluated. As two ongoing studies currently investigate eltrombopag (one already completed, but without published results), we are awaiting results for this drug.
Topics: Adult; Azacitidine; Benzoates; Blood Transfusion; Decitabine; Female; Hemorrhage; Humans; Hydrazines; Lenalidomide; Leukemia, Myeloid, Acute; Male; Myelodysplastic Syndromes; Pyrazoles; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thalidomide; Thrombocytopenia; Thrombopoietin
PubMed: 28962071
DOI: 10.1002/14651858.CD009883.pub2