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Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
Frontiers in Medicine 2023Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually...
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis.
METHODS
We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst.
RESULTS
We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT.
CONCLUSION
Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief.
SYSTEMATIC REVIEW REGISTRATION
www.crd.york.ac.uk/PROSPERO/, CRD42023412467.
PubMed: 38076242
DOI: 10.3389/fmed.2023.1289180 -
Blood Reviews Nov 2023Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation... (Review)
Review
Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.
Topics: Humans; Androgens; Primary Myelofibrosis; Retrospective Studies; Neoplasms; Anemia, Aplastic; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Myeloproliferative Disorders; Thrombocytopenia
PubMed: 37709654
DOI: 10.1016/j.blre.2023.101132 -
Frontiers in Pediatrics 2023Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin... (Review)
Review
BACKGROUND
Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited.
METHODS AND FINDINGS
We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population.
CONCLUSION
Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.
PubMed: 37168802
DOI: 10.3389/fped.2023.1149718 -
Clinical Drug Investigation May 2023Severe aplastic anaemia (SAA) is a syndrome of bone marrow failure caused by T cell-mediated destruction of haematopoietic stem cells and progenitor cells. Whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Severe aplastic anaemia (SAA) is a syndrome of bone marrow failure caused by T cell-mediated destruction of haematopoietic stem cells and progenitor cells. Whether patients with SAA should be treated with eltrombopag (EPAG) and immunosuppressive therapy (IST) or IST alone remains debatable. Therefore, we conducted this meta-analysis to compare the efficacy of eltrombopag + IST with that of IST alone in patients with SAA and to assess the difference in the efficacy of eltrombopag in adults and children.
METHODS
We performed this meta-analysis by retrieving studies that met the inclusion and exclusion criteria from PubMed, EMBASE, and the Cochrane Library up to 1 January 2023. We used a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for primary and secondary outcomes. I statistics were used to evaluate the heterogeneity of the included studies.
RESULTS
Six studies involving a total of 699 patients were included. In terms of the primary outcomes, our pooled results indicated that patients treated with EPAG + IST had a higher 6-month overall response rate (OR = 2.25; 95% CI, 1.60-3.16; p < 0.00001), a higher 6-month complete response rate (OR = 2.61; 95% CI, 1.82-3.74; p < 0.00001), and a lower 6-month nonresponse rate (OR = 0.32; 95% CI, 0.19-0.52; p < 0.00001). However, there was no significant difference in the rate of 6-month partial response (OR = 0.94; 95% CI, 0.49-1.81; p = 0.85).
CONCLUSION
This meta-analysis indicated that patients treated with additional eltrombopag for IST may have a higher rate of haematological response.
Topics: Adult; Child; Humans; Anemia, Aplastic; Immunosuppressive Agents; Immunosuppression Therapy; Benzoates; Treatment Outcome
PubMed: 37165250
DOI: 10.1007/s40261-023-01266-7 -
BMC Oral Health Feb 2023Mucormycosis is a type of fatal infectious disease, rarely involved in the oromaxillofacial region. This study aimed to describe a series of 7 cases with...
PURPOSE
Mucormycosis is a type of fatal infectious disease, rarely involved in the oromaxillofacial region. This study aimed to describe a series of 7 cases with oromaxillofacial mucormycosis and to discuss the epidemiology, clinical features, and treatment algorithm thereof.
METHODOLOGY
Seven patients in the author's affiliation have been treated. They were assessed and presented as per their diagnostic criteria, surgical approach, and mortality rates. Reported cases of mucormycosis originally happened in craniomaxillofacial region were synthesized through a systematic review so as to better discuss its pathogenesis, epidemiology, and management.
RESULTS
Six patients had a primary metabolic disorder, and one immunocompromised patient had a history of aplastic anemia. The criteria for a positive diagnosis of invasive mucormycosis were based on clinical presentation of signs and symptoms, and a biopsy for microbiological culture and histopathologic analysis. Each patient used antifungal drugs and five of them also underwent surgical resection at the same time. Four patients died due to the unregulated spread of mucormycosis, and one patient died owing to her main disease.
CONCLUSIONS
Although uncommon in clinical practice setting, mucormycosis should be of great concern in oral and maxillofacial surgery, due to the life-threatening possibility of this disease. The knowledge of early diagnosis and prompt treatment is of utmost importance for saving lives.
Topics: Humans; Female; Mucormycosis; Retrospective Studies; Antifungal Agents; Biopsy
PubMed: 36810012
DOI: 10.1186/s12903-023-02823-4 -
Frontiers in Endocrinology 2023The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
OBJECTIVE
The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
METHODS
The data of patients with antithyroid drug-induced aplastic anemia were retrieved from PubMed and Wanfang Medical Network databases from 1992 to August 2022. The clinical characteristics, such as age distribution, gender tendency, common symptoms, blood cell count, bone marrow features, treatment strategy, and prognosis, were analyzed.
RESULTS
A total of 17 cases (male:female = 1:16) had been retrieved. Patients' age ranged from 16 to 74 years (median 50 years). Among them, 82.3% (14/17) of the patients were administered methimazole (MMI), and 78.6% of them had MMI ≥30 mg/day. In addition, 88.2% (15/17) of the patients had sore throat and fever, and 47.1% (8/17) of the patients had hemorrhagic symptoms. Aplastic anemia occurred within 6 months after initiation of the antithyroid therapy in 94.1% of the patients. Agranulocytosis (94.1%) was the most common and earliest blood cell change, and 47.1% of the patients experienced progressive platelet decline during the treatment process. The treatments include timely withdrawal of antithyroid drugs, broad-spectrum antibiotics, granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids and other immunosuppressive agents, and supportive treatments such as erythrocyte transfusion and platelet transfusion. Moreover, 70.6% of the patients had complete or near-complete remission within 8 days to 6 weeks.
CONCLUSION
Aplastic anemia is a rare and serious adverse reaction of antithyroid drugs, which is more common in women. It usually occurs during early treatment with high-dose antithyroid drugs. Most patients have a good prognosis after timely drug ceasing and appropriate treatment.
Topics: Female; Humans; Male; Adolescent; Young Adult; Adult; Middle Aged; Aged; Antithyroid Agents; Anemia, Aplastic; Methimazole; Bone Marrow; Glucocorticoids
PubMed: 36777352
DOI: 10.3389/fendo.2023.1064723 -
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 -
Frontiers in Immunology 2022In most patients with aplastic anemia (AA), the diagnosis is limited to a description of the symptoms. Lack of understanding of the underlying pathophysiological...
BACKGROUND
In most patients with aplastic anemia (AA), the diagnosis is limited to a description of the symptoms. Lack of understanding of the underlying pathophysiological mechanisms causing bone marrow failure (BMF), hampers tailored treatment. In these patients, auto-immune cell-mediated destruction of the bone marrow is often presumed to be the causative mechanism. The status of the bone marrow microenvironment, particularly the mesenchymal stromal cell (MSC) component, was recently suggested as a potential player in the pathophysiology of AA. Therefore, functional, and immune modulatory characteristics of bone marrow MSCs might represent important parameters for AA.
OBJECTIVE
To conduct a systematic review to evaluate functional properties of MSCs derived from patients with AA compared to healthy controls.
METHODS
According to PRISMA guidelines, a comprehensive search strategy was performed by using online databases (Pubmed, ISI Web of Science, Embase, and the Cochrane Library). Studies reporting on phenotypical characterization, proliferation potential, differentiation capacity, immunomodulatory potential, and ability to support hematopoiesis were identified and screened using the Rayyan software tool.
RESULTS
23 articles were included in this systematic review, describing a total of 324 patients with AA and 285 controls. None of the studies identified a significant difference in expression of any MSC surface marker between both groups. However, AA-MSCs showed a decreased proliferation potential, an increased tendency to differentiate into the adipogenic lineage and decreased propensity towards osteogenic differentiation. Importantly, AA-MSCs show reduced capacity of immunosuppression and hematopoietic support in comparison to healthy controls.
CONCLUSION
We conclude that there are indications for a contribution of MSCs in the pathophysiology of AA. However, the current evidence is of poor quality and requires better defined study populations in addition to a more robust methodology to study MSC biology at a cellular and molecular level. Future studies on bone marrow microenvironment should aim at elucidating the interaction between MSCs, hematopoietic stem cells (HSCs) and immune cells to identify impairments associated with/causing BMF in patients with AA.
Topics: Anemia, Aplastic; Bone Marrow; Cell Differentiation; Humans; Mesenchymal Stem Cells; Osteogenesis
PubMed: 35355996
DOI: 10.3389/fimmu.2022.859668 -
Transplantation and Cellular Therapy Feb 2022Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard... (Meta-Analysis)
Meta-Analysis
Upfront Alternative Donor Transplant versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack a Fully HLA-Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies, on Behalf of the Severe Aplastic Anemia Working Party of the European Group for...
Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Topics: Anemia, Aplastic; Bone Marrow; Child; Graft vs Host Disease; Humans; Immunosuppression Therapy; Retrospective Studies
PubMed: 34649020
DOI: 10.1016/j.jtct.2021.10.006