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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 -
Head & Neck Dec 2022This study aimed to map systemic alterations predisposing to oral squamous cell carcinoma (OSCC) onset. This review was conducted according to the Preferred Reporting... (Meta-Analysis)
Meta-Analysis
This study aimed to map systemic alterations predisposing to oral squamous cell carcinoma (OSCC) onset. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Five databases were used to access (1) reports of OSCC co-occurring in patients with systemic conditions, (2) prevalence of OSCC among these patients, and (3) clinicopathological profiles. Data from more than 1 million patients worldwide showed that Fanconi's anemia, xeroderma pigmentosum, dyskeratosis congenital, chronic fatigue syndrome, and patients post bone marrow transplantation (BMT) present increased risk for OSCC development. The overall prevalence of OSCC in syndromic patients and post-BMT were 0.65% (95% CI = 0.13-3.11, p < 0.01) and 5.83% (95% CI = 0.00-30.90, p < 0.01), respectively. The certainty of the evidence was moderate. This study demonstrated that some systemic conditions predispose to OSCC. These results present an impact on the screening of OSCC in systemically compromised patients.
Topics: Humans; Carcinoma, Squamous Cell; Fanconi Anemia; Head and Neck Neoplasms; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 36114663
DOI: 10.1002/hed.27193 -
Expert Review of Hematology Jun 2022COVID-19 crisis continues around the world. Some patients developed complications after the disease, which have been reported in limited studies. The aim of this study...
INTRODUCTION
COVID-19 crisis continues around the world. Some patients developed complications after the disease, which have been reported in limited studies. The aim of this study is to comprehensively assess the post-COVID hematologic complications in patients.
AREAS COVERED
We searched PubMed, Scopus, and Google Scholar between January 2020 and August 2021 using related keywords. Evaluation of the article was performed by two independent researchers. The extracted data included the number of patients, age, type of hematological complication, duration of follow-up, response to treatment and prognosis.
EXPERT OPINION
Sixty-five articles reported post-COVID hematologic complications. The most frequent hematologic complication in COVID-19 patients is thromboembolic events, which often occur in two forms: deep vein thrombosis (DVT) and pulmonary embolism (PE). In a group of patients after the diagnosis of COVID-19, a significant decrease in platelets was observed, which was attributed to the ITP induced by COVID-19. Hemolytic anemia and aplastic anemia have also been reported rarely in patients. Finally, post-COVID hematologic complications appear to go beyond thromboembolic events. Although these complications have rarely been reported, searching for methods to identify susceptible patients and prevent these complications could be the subject of future research.
Topics: COVID-19; Humans; Pulmonary Embolism; Thromboembolism; Venous Thrombosis
PubMed: 35584541
DOI: 10.1080/17474086.2022.2080051 -
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 -
Journal of Neuro-ophthalmology : the... Mar 2022Idiopathic intracranial hypertension (IIH) is a condition typically affecting young, obese women. Although anemia is recognized as a risk factor of IIH from case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic intracranial hypertension (IIH) is a condition typically affecting young, obese women. Although anemia is recognized as a risk factor of IIH from case reports, their relationship remains controversial as several comparative studies showed no significant association. This study aimed to examine the relationship between anemia and IIH.
METHODS
MEDLINE, Embase, Cochrane Library, and grey literature were searched to September 2020. Primary studies on patients with diagnoses of anemia of any kind and IIH were included. Primary outcomes included the total number of cases of anemia and IIH. A meta-analysis on the prevalence of anemia in IIH compared with control patients was conducted. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the quality of evidence.
RESULTS
Overall, 62 cases and 5 observational or case-control studies were included. Pooled incidence of anemia in patients with IIH was 195/1,073 (18.2%). Patients with IIH (n = 774) had a significantly higher prevalence of anemia compared with controls (n = 230,981) (RR 1.44 [95% confidence interval 1.08-1.92]). Patients were 67.7% females and had a mean age of 22.4 years. The mean opening pressure was 37.9 cmH2O. Anemia was most commonly caused by iron deficiency (51.6%) and aplastic anemia (19.4%). Most patients (59.7%) showed improvement or resolution with anemia treatment only without intracranial pressure-lowering therapy. Evidence was limited because of high risk of reporting bias from the large number of case reports and case-control studies.
CONCLUSIONS
Anemia is significantly more common in IIH compared with control patients, and case reports suggest a direct relationship. Complete blood counts should be considered in all patients with papilledema, particularly in atypical presentations (male, nonobese, nonperipapillary retinal hemorrhages, prominent risk factor for anemia) or in treatment-refractory IIH.
Topics: Adult; Anemia; Case-Control Studies; Female; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Papilledema; Pseudotumor Cerebri; Young Adult
PubMed: 34812762
DOI: 10.1097/WNO.0000000000001408 -
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 -
Medicina (Kaunas, Lithuania) Jun 2021Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a... (Review)
Review
Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. : A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. : To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. : Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.
Topics: Adult; Child; Enterocolitis, Neutropenic; Humans; Lymphoma; Neoplasms; Prognosis; Sepsis
PubMed: 34203105
DOI: 10.3390/medicina57060638 -
Annals of Palliative Medicine May 2021When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the standard immunosuppressive treatment plan, and ATG is the main mode to treat severe aplastic anemia. A large number of prospective studies and clinical trials have confirmed the clinical application value of eltrombopag in aplastic anemia. Although ATG combined with eltrombopag brings satisfactory treatment results, the safety of long-term use is still unclear. Therefore, more clinical trial studies are needed to verify its safety.
METHODS
Literature in the Chinese and English medical databases was searched using the following search terms: "Antithymocyte globulin", "severed aplastic anemia" and "eltrombopag". Patients in the experimental group were administered ATG combined with eltrombopag and patients in the control group received ATG treatment alone. Rev Man5.3 software was used for meta-analysis.
RESULTS
A total of 16 references were included in this meta-analysis. Heterogeneity tests examining total effective rate demonstrated that Chi2 =4.48, df =15, I2=0%<50%, and P=1.00>0.01. The effective rate of the experimental group was higher than that of the control group, with odds ratio (OR) =1.90 and 95% confidence interval (CI) 1.35 to 2.68 (Z=3.70, P=0.0002). The heterogeneity test results of the survival rate within 2 years were Chi2 =3.09, df =7, I2=0%<50%, and P=0.88>0.01. The survival rate of the experimental group was higher than that of the control group, with OR =2.54, and 95% CI: 1.58 to 4.09 (Z=3.84, P=0.0001). The heterogeneity test results of the mortality rate were Chi2 =3.49, df =6, I2=0%<50%, and P=0.75>0.01. The mortality rate of the experimental group was lower than that of the control group, with OR =0.48 and 95% CI: 0.33 to 0.70 (Z=3.84, P=0.0001). The heterogeneity test results of the occurrence of side effects were Chi2 =0.12, df =3, I2=0%<50%, P=0.99>0.01. The incidence of side effects in the experimental group was lower than that in the control group, with OR =0.74, 95% CI: 0.48 to 1.17 (Z=1.29, P=0.20).
DISCUSSION
This meta-analysis demonstrated that the combination of ATG with eltrombopag in the treatment of SAA is safer and more effective than ATG alone.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Benzoates; Humans; Hydrazines; Prospective Studies; Pyrazoles; Treatment Outcome
PubMed: 34107711
DOI: 10.21037/apm-21-1049 -
Clinical Cancer Research : An Official... Oct 2021Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection toward multiple malignancies, including a greater...
Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection toward multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia-associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiotherapy to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 patients with FA-HNSCC including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, radiotherapy, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation. Although there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.
Topics: Carcinoma, Squamous Cell; Fanconi Anemia; Head and Neck Neoplasms; Humans; Squamous Cell Carcinoma of Head and Neck
PubMed: 34045293
DOI: 10.1158/1078-0432.CCR-21-1259 -
Frontiers in Oncology 2021This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell...
Comparisons Between Frontline Therapy and a Combination of Eltrombopag Plus Immunosuppression Therapy and Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Severe Aplastic Anemia: A Systematic Review.
This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the frontline treatment for severe aplastic anemia (SAA) patients. Four electronic databases and Clinicaltrials.gov were comprehensively searched from January 2010 to August 2020. Studies that aimed at evaluating the efficacy and safety of EPAG+IST or haplo-HSCT in SAA patients were included. One-/2-year overall survival (OS), complete response (CR), and overall response rates (ORRs) were indirectly compared between EPAG+IST and haplo-HSCT. A total of 447 patients involved in 10 cohort studies were found to be eligible for this study. A narrative synthesis was performed due to lack of data directly comparing the outcome of EPAG+IST and haplo-HSCT. Consistent with the analysis results in the whole population, subgroup analyses in the age-matched population showed that there was no significant difference in ORR between EPAG+IST and haplo-HSCT groups. However, the CR rate was lower in the EPAG+IST group when compared with the haplo-HSCT group. The incidence rate of clonal evolution/SAA relapse ranged at 8-14 and 19-31% in the EPAG+IST group but not reported in the haplo-HSCT group. The incidence rate for acute graft vs. host disease (aGVHD) and chronic graft vs. host disease (cGVHD) ranged at 52-57 and 12-67%, respectively, for the haplo-HSCT group. The main causes of deaths were infections in the EPAG+IST group, and GVHD and infections in the haplo-HSCT group. EPAG+IST has a comparable ORR and 1-/2-year OS but lower CR rate when indirectly compared with haplo-HSCT in the frontline treatment of patients with SAA. Patients treated with haplo-HSCT may exhibit a high incidence of GVHD, whereas patients treated with EPAG+IST may experience more relapses or clone evolution.
PubMed: 33981596
DOI: 10.3389/fonc.2021.614965