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BMC Cancer Aug 2023Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.
BACKGROUND
Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic hematopoietic cell transplantation. Venetoclax-based therapies have been increasingly used for treating post-transplantation relapse of AML. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Venetoclax combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation.
METHODS
We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literatures. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI).
RESULTS
This meta-analysis included 10 studies involving a total of 243 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Venetoclax combined with HMAs for post-transplantation relapse in AML/MDS was 32% (95% CI, 26-39%, I = 0%), with an overall response rate of 48% (95% CI, 39-56%, I = 37%). The 6-month survival rate was 42% (95% CI, 29-55%, I = 62%) and the 1-year survival rate was 23% (95% CI, 11-38%, I = 78%).
CONCLUSION
This study demonstrated a moderate benefit of Venetoclax in combination with HMAs for patients with relapsed AML/MDS post-transplantation (including those who have received prior HMAs therapy), and may become one of treatment options in the future. Large-scale prospective studies are needed to confirm the potential benefit from venetoclax combined with HMAs.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Bridged Bicyclo Compounds, Heterocyclic; Leukemia, Myeloid, Acute; Chronic Disease; Myelodysplastic Syndromes; Neoplasms, Second Primary
PubMed: 37592239
DOI: 10.1186/s12885-023-11259-6 -
Blood Reviews Sep 2023Anemia is common in Myelodysplastic Syndromes (MDS). Different anemia treatments have been tested in clinical studies, but the full impact on patients' health-related... (Review)
Review
Anemia is common in Myelodysplastic Syndromes (MDS). Different anemia treatments have been tested in clinical studies, but the full impact on patients' health-related quality of life (HRQoL) and physical function is unknown. The main aim of this review was to assess whether improvements in anemia are associated with changes in HRQoL/physical function. Twenty-six full-text publications were identified, enrolling 2211 patients: nine randomized trials (RCTs), fourteen non-randomized studies of interventions and three cross-sectional studies. Interventions included: growth factors/erythropoiesis-stimulating agents (n = 14), red cell transfusion (n = 9), erythroid maturation agents (n = 1), or a combination (n = 2). Five RCTs reported no changes in HRQoL despite erythroid response to the intervention, raising the question of whether anemia treatment alone can effectively improve HRQoL. Many studies were considered at high risk of bias for assessing HRQoL. There is a pressing need for future clinical trials to better define the nature of the relationship between anemia and HRQoL/functional outcomes.
Topics: Humans; Anemia; Myelodysplastic Syndromes; Hematinics; Erythrocyte Transfusion; Quality of Life
PubMed: 37479599
DOI: 10.1016/j.blre.2023.101114 -
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 -
Advances in Therapy Jun 2023Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making...
INTRODUCTION
Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making complement inhibition the best approach to manage PNH. Three complement inhibitors are approved by the European Medicines Agency as targeted therapy for PNH: eculizumab and ravulizumab, two humanized monoclonal antibodies targeting the same complement 5 (C5) epitope, approved in 2007 and 2019, respectively, and the more recently approved cyclic peptide, the complement 3 (C3) inhibitor pegcetacoplan. Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial evidence. Given the lack of evidence-based data for some clinical situations encountered in real life, we identified specific populations of patients who may benefit from switching to proximal C3 from terminal C5 inhibition.
METHODS
The expert recommendations presented here were created using a Delphi-like process by a group of expert PNH specialists across Central Europe. Based on an initial advisory board meeting discussion, recommendations were prepared and reviewed as part of a Delphi survey to test agreement.
RESULTS
Using a systematic approach, literature databases were searched for relevant studies, and 50 articles were reviewed by the experts and included as supporting evidence.
CONCLUSION
Implementation of these recommendations uniformly across healthcare institutions will promote the best use of complement inhibition in managing PNH, and has the potential to positively impact patient outcomes in Central Europe and worldwide.
Topics: Humans; Hemoglobinuria, Paroxysmal; Expert Testimony; Complement Inactivating Agents; Complement C3; Complement C5; Europe
PubMed: 37072660
DOI: 10.1007/s12325-023-02510-4 -
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 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2023The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.
MATERIALS AND METHODS
We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects.
RESULTS
The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%.
CONCLUSIONS
The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.
Topics: Humans; Azacitidine; Antimetabolites, Antineoplastic; Myelodysplastic Syndromes; Treatment Outcome; Remission Induction
PubMed: 36428152
DOI: 10.1016/j.clml.2022.11.002 -
Medicine Nov 2022Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients...
INTRODUCTION
Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature.
PATIENT CONCERNS AND DIAGNOSIS
We report a 38-year-old woman with Ph-positive MDS.
INTERVENTIONS AND OUTCOMES
She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed.
CONCLUSION
Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.
Topics: Humans; Female; Adult; Philadelphia Chromosome; Transplantation, Homologous; Rare Diseases; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation
PubMed: 36401464
DOI: 10.1097/MD.0000000000031874 -
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 -
Medicine Oct 2022Immunosuppressive therapy is the frontline treatment for aplastic anemia patients ineligible for transplantation. The long-term effects of hematopoietic growth factors... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Immunosuppressive therapy is the frontline treatment for aplastic anemia patients ineligible for transplantation. The long-term effects of hematopoietic growth factors (HGF) added to standard immunosuppressive therapy are still unclear. We performed a systematic review and meta-analysis to clarify this issue.
METHODS
A comprehensive search of databases was conducted including 5 international electronic databases (Cochrane, PubMed, Embase, Web of Science, and LILACS) and 4 Chinese electronic databases (Chinese Bio-medicine Database, Chinese National Knowledge Infrastructure, WanFang Data, and China Science and Technology Journal Database databases) from database inception until February, 2022. We included randomized controlled trials that assigned patients with acquired aplastic anemia treated with immunosuppressive therapy (IST), which compared between the addition of HGF and placebo or no treatment. The co-primary outcome were the overall survival (OS) and late clonal malignant evolution at the end of follow-up.
RESULTS
Nine randomized controlled trials including 719 participants were identified. The addition of growth factors to immunosuppression yielded no difference in OS (relative risks [RR], 1.08, 95% confidence interval [CI] 0.99-1.18). HGF was not associated with higher occurrence of secondary myelodysplastic syndromes/acute myeloid leukemia (RR, 1.09, 95% CI 0.43-2.78) or paroxysmal nocturnal hemoglobulinemia (RR, 1.38, 95% CI 0.68-2.81) at the end of follow-up. No difference were found in overall response (RR, 1.16, 95% CI 0.98-1.37), infections occurrence (RR, 0.82; 95% CI, 0.51-1.31) or relapse (RR, 0.65; 95% CI, 0.37-1.13).
CONCLUSIONS
HGF as an adjunct to IST has no impact on long-term OS, late clonal malignant evolution, response rate, relapse or infections occurrence. HGF could be added to standard IST for high-risk patients with delayed neutrophil recovery without concern for long-term consequences but could not be recommended as routine clinical practice.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42021275188.
Topics: Humans; Anemia, Aplastic; Randomized Controlled Trials as Topic; Immunosuppression Therapy; Immunosuppressive Agents; Immunologic Deficiency Syndromes; Recurrence
PubMed: 36281138
DOI: 10.1097/MD.0000000000031103 -
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