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Journal of the American Academy of... Jun 2024
Review
PubMed: 38906261
DOI: 10.1016/j.jaad.2024.05.086 -
Haematologica Feb 2010Hypomethylating agents have recently been shown to improve the outcome of patients with myelodysplastic syndrome. A meta-analysis and systematic review was carried out... (Comparative Study)
Comparative Study Meta-Analysis
Hypomethylating agents have recently been shown to improve the outcome of patients with myelodysplastic syndrome. A meta-analysis and systematic review was carried out of randomized controlled trials comparing treatment with hypomethylating agents to conventional care, i.e., best supportive care or chemotherapy, in patients with myelodysplastic syndrome. The outcomes assessed were overall survival, time to transformation or death, overall response rate and toxicity. Hazard ratios with 95% confidence intervals were estimated and pooled for time-to-event data. For dichotomous data, relative risks were estimated and pooled. Four trials including 952 patients examined the effect of 5-azacitidine and decitabine. Treatment with hypomethylating agents significantly improved overall survival (hazard ratio 0.72, 95% confidence interval 0.60-0.85, three trials) and time to transformation or death (hazard ratio 0.69, 95% confidence interval 0.58-0.82, four trials). In a subgroup analysis per type of drug, these benefits could be shown for 5-azacitidine but not for decitabine. Both agents favorably influenced response rates. A higher rate of grade 3/4 adverse events was observed with their use. Since 5-azacitidine prolongs overall survival and time to transformation or death it should be highly considered in the treatment of patients with high-risk myelodysplastic syndrome. Further studies are needed to establish the exact role of decitabine compared to 5-azacitidine in these patients.
Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Azacitidine; Decitabine; Humans; Middle Aged; Myelodysplastic Syndromes; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome
PubMed: 19773261
DOI: 10.3324/haematol.2009.010611 -
British Journal of Haematology Sep 2016We conducted a systematic review and meta-analysis to estimate the efficacy of darbepoetin alpha (DA) for treatment of myelodysplastic syndrome (MDS)-related anaemia.... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to estimate the efficacy of darbepoetin alpha (DA) for treatment of myelodysplastic syndrome (MDS)-related anaemia. Eligible studies were prospective, interventional, and reported World Health Organization, French-American-British, or International Prognostic Scoring System (IPSS) criteria. Outcomes included erythroid response rate (primary); haemoglobin response; change in haemoglobin, transfusion status, and quality-of-life (QoL); and safety. Ten studies (N = 647) were analysed. Erythroid response rate range was 38-72%; median response duration range was 12-51+ months. Patients with erythropoietin (EPO) <100 iu/l had 35% [95% confidence interval (CI): 22-48%; P < 0·001) better response than patients with EPO >100 iu/l. Erythropoesis-stimulating agent (ESA)-naïve patients had 17% (95% CI: 3-32%; P = 0·022) greater response rate than those previously treated with ESA. Nonetheless, previously treated patients had response rates of 25-75%. Higher baseline haemoglobin levels, higher dose, transfusion-independence and low-risk IPSS status were reported by several studies to be associated with better response. QoL, transfusion rates and haemoglobin levels improved with treatment. Hypertension, thromboembolism and progression to acute myeloid leukaemia were reported in 2%, 1% and 1% of patients, respectively. This meta-analysis suggests that DA treatment can be useful for improving erythroid response in MDS patients with anaemia, even among patients previously treated with ESA.
Topics: Blood Transfusion; Darbepoetin alfa; Hemoglobins; Humans; Myelodysplastic Syndromes; Quality of Life; Treatment Outcome
PubMed: 27214305
DOI: 10.1111/bjh.14116 -
Rheumatology International Jul 2024VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1... (Review)
Review Meta-Analysis
BACKGROUND
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow.
METHODS
We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers.
RESULTS
From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants.
CONCLUSION
VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.
Topics: Humans; Male; Ubiquitin-Activating Enzymes; Female; Mutation; Syndrome; Aged; Middle Aged; Myelodysplastic Syndromes; Sweet Syndrome; Polyarteritis Nodosa; Hereditary Autoinflammatory Diseases
PubMed: 38129348
DOI: 10.1007/s00296-023-05513-0 -
Frontiers in Oncology 2020Many studies aimed to evaluate the efficacy and safety of treosulfan-based conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) compared...
Long-Term Outcomes of Treosulfan- vs. Busulfan-Based Conditioning Regimen for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia Before Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
BACKGROUND
Many studies aimed to evaluate the efficacy and safety of treosulfan-based conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) compared with other regimens, but different outcomes were reported across studies.
AIM
To determine the long-term survival outcomes of treosulfan-based vs. busulfan-based conditioning regimens in myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) patients.
METHODS
PubMed, Embase, and Cochrane library were searched for studies published prior to December 6, 2019. The fixed-effects model was applied for overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), acute and chronic graft versus host disease (GvHD). Relapse incidence (RI) was pooled by the use of the random-effects model.
RESULTS
Six studies were included (3,982 patients; range, 57-1,956). The pooled HR for OS favored treosulfan (HR=0.80, 95%CI: 0.71-0.90). There was no significant difference in NRM between the two regimens (HR=0.84, 95%CI=0.71-1.01). There was no significant difference in LFS between the two regimens (HR=0.98, 95%CI=0.87-1.12). Treosulfan-based regimens showed a lower risk of aGvHD (HR=0.70, 95%CI=0.59-0.82), but there was no difference for cGvHD (HR=0.94, 95%CI=0.81-1.09). There was no significant difference in RI between the two regimens (HR=0.96, 95%CI=0.71-1.31). There was no publication bias among these studies.
CONCLUSION
The current meta-analysis determined that treosulfan-based conditioning regimens could improve the OS in patients with MDS and AML, with lower acute graft-versus-host disease incidence, compared with busulfan-based regimens.
PubMed: 33425740
DOI: 10.3389/fonc.2020.591363 -
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 -
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 -
Frontiers in Pharmacology 2023[This corrects the article DOI: 10.3389/fphar.2021.701690.].
Erratum: Comparison between decitabine and azacitidine for patients with acute myeloid leukemia and higher-risk myelodysplastic syndrome: a systematic review and network meta-analysis.
[This corrects the article DOI: 10.3389/fphar.2021.701690.].
PubMed: 37214470
DOI: 10.3389/fphar.2023.1213053 -
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 -
International Journal of Clinical and... 2014We performed a systematic review and meta-analysis to compare the clinical outcomes and toxicity of reduced-intensity conditioning (RIC) and myeloablative conditioning...
Reduced-intensity and myeloablative conditioning allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome: a meta-analysis and systematic review.
BACKGROUND
We performed a systematic review and meta-analysis to compare the clinical outcomes and toxicity of reduced-intensity conditioning (RIC) and myeloablative conditioning (MAC) allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
EVIDENCE ACQUISITION
A comprehensive PubMed and Embase search was performed using the following keywords: "reduced-intensity", "myeloablative", "AML", and "MDS". The primary endpoints were overall survival (OS) and event-free survival (EFS), and the secondary endpoints were relapse incidence (RI), non-relapse mortality (NRM), grade II-IV acute graft-versus-host disease (aGVHD), and chronic GVHD (cGVHD).
RESULTS
Eight studies (2 prospective and 6 retrospective) involving 6464 patients who received RIC (n = 1571) or MAC (n = 4893) alloHSCT were included in the analysis. Median age and the number of patients with low hematopoietic cell transplantation-specific comorbidity index scores and who received ex vivo or in vivo T cell depletion were higher in the RIC arm than in the MAC arm. Significant heterogeneity was not found among the studies for any of the endpoints except for grade II-IV aGVHD. OS (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.84-1.08; p = 0.47) and EFS (OR, 0.88; 95% CI, 0.77-1.00; p = 0.05) were similar in the RIC and MAC arms, whereas RI (OR, 1.41; 95% CI, 1.24-1.59; p < 0.00001) was higher in the RIC arm than in the MAC arm. The incidence of grade II-IV aGVHD (OR, 0.59; 95% CI, 0.36-0.96; p = 0.03) was lower in the RIC arm than in the MAC arm; however, NRM (OR, 0.99; 95% CI, 0.87-1.13; p = 0.85), total cGVHD (OR, 1.10; 95% CI, 0.88-1.38; p = 0.38), and extensive cGVHD (OR, 1.01; 95% CI, 0.75-1.37; p = 0.95) were not significantly different between the two arms.
CONCLUSION
RIC alloHSCT may be an effective treatment strategy for AML/MDS patients who are not suitable candidates for MAC alloHSCT. However, heterogeneity in baseline patient characteristics and treatment protocols may have influenced the outcomes of RIC alloHSCT in our analysis. Future randomized controlled trials are needed to confirm our findings.
PubMed: 25550955
DOI: No ID Found