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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 -
Medicine Nov 2022Systemic inflammatory and autoimmune manifestations (SIAMs) are frequently reported in Myelodysplastic syndromes (MDS). Studies focused on the impact of SIMAs on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic inflammatory and autoimmune manifestations (SIAMs) are frequently reported in Myelodysplastic syndromes (MDS). Studies focused on the impact of SIMAs on survival outcomes of MDS remains controversial. We performed this systematic review and meta-analysis to determine the association of SIAMs with overall survival, median survival, rate of acute myeloid leukemia transformation and mortality of MDS.
MATERIALS AND METHODS
An electronic search was conducted in 4 databases without any language restrictions, including PubMed, EMBASE, Medicine and Cochrane library up to April 30, 2021.
RESULTS
The 18 studies included a total of 4603 MDS patients, of which 1175 (25.5%) patients had SIAMs. MDS patients with SIAMs had a statistically shorter overall survival compared with patient without SIAMs (Hazard ratio, 2.43; 95% confidence interval [CI], 1.34-4.41; P < .01). Our results were most compatible with no effect of SIAMs on median survival, rate of acute myeloid leukemia transformation and mortality (Median survival ratio, 1.16; 95% CI, 0.91-1.47; Odds ratio, 0.96; 95% CI, 0.63-1.45 and 1.2; 95% CI, 0.84-1.7, respectively).
CONCLUSION
In this systematic review and meta-analysis, SIAMs appeared to have an adverse effect on overall survival of MDS patients. This finding suggested that SIAMs may be a potential independent prognostic factor for MDS.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 36401363
DOI: 10.1097/MD.0000000000031427 -
Journal of Cancer 2020Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning...
Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis.
Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning (MAC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the evidence regarding the optimal conditioning intensity in younger patients with AML or MDS is weak and contradictory. PubMed, Medline, Embase, and other online sources were searched from the initial period to February 25, 2020. Odds ratios and 95% confidence intervals were calculated to estimate pooling effects. Four randomized controlled trials (RCTs) about conditioning intensity involving 633 patients were included. There were no significant differences of 1/2/4/5 years progression-free survival (PFS) and relapse incidence (RI) between two conditioning intensities. Overall survival (OS) was similar at 1/2/4 years, but patients receiving RIC had a higher OS at 5 years. Additionally, RIC were associated with lower non-relapse mortality, less grade II-IV and grade III-IV acute graft-versus-host disease (GVHD), and lower incidence of chronic GVHD compared with MAC regimens. Subgroup analysis showed similar OS and RI for AML patients, and there was a trend towards lower NRM and grade II-IV aGVHD in RIC group. Available data for MDS indicated that OS, PFS, and RI were comparable. For intermediate-risk patients, there was no evidence that RIC is inferior to MAC. However, for high-risk patients, MAC tends to perform better. Based on the above results, it might be concluded that RIC is a feasible treatment option for adults with AML or MDS younger than 66 years, particularly those with intermediate-risk disease. Future RCTs incorporating of risk stratifications are warranted to guide the optimal decision under certain conditions.
PubMed: 32742468
DOI: 10.7150/jca.46081 -
PloS One 2016Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS)... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Lenalidomide for Treatment of Low-/Intermediate-1-Risk Myelodysplastic Syndromes with or without 5q Deletion: A Systematic Review and Meta-Analysis.
BACKGROUND
Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial.
METHOD
A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS. Efficacy was assessed according to erythroid hematologic response (HI-E), cytogenetic response (CyR), OS and AML progression. Safety was evaluated based on the occurrence rates of grades 3-4 adverse events (AEs).
RESULTS
Seventeen studies were included consisting of a total of 2160 patients. The analysis indicated that the overall rate of HI-E was 58% with 95% confidence interval (CI) of 43-74%. The pooled estimates for the rates of CyR, complete CyR, and partial CyR were 44% (95% CI 19-68%), 21% (95% CI 13-30%) and 23% (95% CI 15-32%), respectively. The patients with 5q deletion had significantly higher rate of HI-E and CyR than those without 5q deletion (P = 0.002 and 0.001, respectively). The incidences of grades 3-4 neutropenia, thrombocytopenia, leukopenia, anemia, deep vein thrombosis, diarrhea, fatigue and rash were 51% (95% CI 30-73%), 31% (95% CI 20-42%), 9% (95% CI 5-13%), 7% (95% CI 2-12%), 3% (95% CI 2-5%), 3% (95% CI 1-5%), 2% (95% CI 1-4%) and 2% (95% CI 1-3%), respectively. Lenalidomide significantly improved OS (HR: 0.62, 95% CI 0.47-0.83, P = 0.001) and lowered the risk of AML progression in del(5q) patients (RR: 0.61, 95% CI 0.41-0.91, P = 0.014).
CONCLUSIONS
In spite of the AEs, lenalidomide could be effectively and safely used for the treatment of lower-risk MDS patients with or without 5q deletion.
Topics: Anemia, Macrocytic; Chromosome Deletion; Chromosomes, Human, Pair 5; Humans; Immunologic Factors; Lenalidomide; Myelodysplastic Syndromes; Thalidomide; Treatment Outcome
PubMed: 27824902
DOI: 10.1371/journal.pone.0165948 -
Medicine Aug 2018Hypomethylating agents (HMAs) are believed to have reliable efficacy in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Meanwhile, the adverse... (Meta-Analysis)
Meta-Analysis Review
Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukopenia: A systematic review and meta-analysis.
BACKGROUND
Hypomethylating agents (HMAs) are believed to have reliable efficacy in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Meanwhile, the adverse events of HMAs have become an increasing concern. There is, however, no systematic meta-analysis available to evaluate overall hematologic toxicities for HMAs. In this meta-analysis, we aim to determine the risk of hematologic toxicities in patients treated with HMAs.
METHODS
Relevant studies were identified from PubMed, Embase, Cochrane Library, and the Clinical Trials. gov databases incepted to February 2018. All phase II and III trials meeting the inclusion criteria included adequate safety data. We calculated the relative risk (RR) of high-grade hematologic toxicities (HTEs) with corresponding 95% CI using Review Manager. The incidences of HTEs were also evaluated by R. Heterogeneity was calculated and reported mainly via I analyses.
RESULTS
A total of 2337 MDS or AML patients from 14 studies were identified in this meta-analysis. The overall incidences of high-grade hematologic toxicities in patients who received HMAs were: 27% of the patients with anemia, 45% with neutropenia, 38% with thrombocytopenia, and 25% with febrile neutropenia, respectively. There was a significantly increased RR of neutropenia and thrombocytopenia using HMAs, in comparison with conventional care regimens (CCR) based on the drug type (decitabine vs azacitidine).
CONCLUSIONS
We conclude that the use of HMAs are associated with an increased risk of neutropenia and thrombocytopenia in MDS or AML patients, and our results also demonstrate that HMAs exposure does not significantly increase the risk of high-grade anemia, leukopenia, or febrile neutropenia compared with CCR.
Topics: Antimetabolites, Antineoplastic; Hematologic Diseases; Humans; Incidence; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Risk
PubMed: 30142779
DOI: 10.1097/MD.0000000000011860 -
The Oncologist Oct 2007The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS).
METHOD
A systematic review and meta-analysis was conducted covering English-language studies published from 1980 to December 2005.
RESULTS
Fifty-nine studies qualified: five controlled trials (n = 354), all epoetin versus control (EvC); 51 epoetin single-arm studies (n = 1,650); and three darbepoetin single-arm studies (n = 102). In the EvC studies, epoetin patients demonstrated a significant advantage over controls in terms of hemoglobin (Hb) response (odds ratio, 5.2; 95% confidence interval, 2.5-10.8). Hb response was 48.1% in single-arm darbepoetin studies, 32.1% in epoetin single-arm studies, and 27.3% in EvC studies. Major Hb response averaged 38.8% in darbepoetin studies, 24.5% in epoetin single-arm studies, and 11.4% in EvC studies. Stratified analyses suggest that lower baseline erythropoietin levels, longer treatment durations, and concurrent iron may be associated with greater Hb response to ESPs. None of the analyzable predictors of Hb response (gender, baseline Hb, ESP type, and ESP duration) were significant in meta-regression analyses. In the few studies with quality-of-life measures, ESP groups attained a pre-post change (Functional Assessment of Cancer Therapy - Fatigue) that exceeded minimum clinically important differences. Selected adverse event rates did not differ between the epoetin and darbepoetin groups.
CONCLUSION
Published studies suggest that ESPs are efficacious in anemia of MDS. Hb response appears higher in darbepoetin patients than in epoetin patients, and safety appears comparable, but darbepoetin data are sparse, and there are as yet no direct comparison studies.
Topics: Erythropoiesis; Erythropoietin; Humans; Myelodysplastic Syndromes; Safety
PubMed: 17962620
DOI: 10.1634/theoncologist.12-10-1264 -
Leukemia & Lymphoma Nov 2022We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We... (Meta-Analysis)
Meta-Analysis
We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We performed a literature search on PubMed, Cochrane Library, EMBASE, and Clinicaltrials.gov. After screening 2004 manuscripts, 16 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. We analyzed the outcomes of 373 patients from 11 retrospective studies and five phase 1 b clinical trials. Pooled complete response with or without hematological recovery was 60% (95% CI 0.49-0.7, = 67%, = 373). Hematopoietic cell transplantation was performed in 32% of patients (95% CI 0.2-0.46, = 62%, = 187). Overall mortality was 45% (95% CI 0.31-0.59, =54%, = 140). VEN-HMA combination therapy demonstrated promising outcomes in MDS. Prospective randomized data is needed to ascertain the benefit of VEN and its impact in MDS patients.
Topics: Humans; Retrospective Studies; Prospective Studies; Antimetabolites, Antineoplastic; Myelodysplastic Syndromes
PubMed: 35687838
DOI: 10.1080/10428194.2022.2084730 -
Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Leukemia Research Nov 2021The value of pre-transplant cytoreductive therapy for patients with myelodysplastic syndromes (MDS) is controversial. Here, we conducted a meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The value of pre-transplant cytoreductive therapy for patients with myelodysplastic syndromes (MDS) is controversial. Here, we conducted a meta-analysis to explore the effects of cytoreduction before transplantation.
METHODS
PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies comparing post-transplant outcomes in MDS patients receiving different pre-transplant therapy. Pooled hazard ratios (HRs) and 95 % confidence intervals (CI) were calculated.
RESULTS
Eighteen reports were included. Post-transplant outcomes were similar for MDS patients receiving pre-transplant cytoreductive therapy and upfront transplantation in terms of overall survival (OS: HR, 0.92; 95 % CI, 0.79-1.07), relapse-free survival (RFS: HR, 1.18; 95 % CI, 0.94-1.47), cumulative incidence of relapse (CIR: HR, 1.08; 95 % CI, 0.88-1.33), and non-relapse mortality (NRM: HR, 0.93; 95 % CI, 0.74-1.18). Pre-transplant hypomethylating agents (HMAs) and chemotherapy were not different regarding post-transplant OS, RFS, CIR, and NRM. Achieving complete remission (CR) before transplantation was associated with increased RFS (HR, 0.80; 95 %CI, 0.63-1.00) and decreased NRM (HR, 0.53; 95 % CI, 0.32-0.90) when compared with upfront transplantation.
CONCLUSIONS
Timely transplantation is of great value for MDS patients. Suitable pre-transplant cytoreduction could be used during the search for donors.
Topics: Cytoreduction Surgical Procedures; Hematopoietic Stem Cell Transplantation; Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 34217112
DOI: 10.1016/j.leukres.2021.106645 -
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