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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 -
BMJ Open Jul 2014Acquired severe aplastic anaemia is a rare and potentially fatal disease. The aim of this Cochrane review was to evaluate the effectiveness and adverse events of... (Comparative Study)
Comparative Study Review
OBJECTIVES
Acquired severe aplastic anaemia is a rare and potentially fatal disease. The aim of this Cochrane review was to evaluate the effectiveness and adverse events of first-line allogeneic haematopoietic stem cell transplantation of human leucocyte antigen (HLA)-matched sibling donors compared with first-line immunosuppressive therapy.
SETTING
Specialised stem cell transplantations units in primary care hospitals.
PARTICIPANTS
We included 302 participants with newly diagnosed acquired severe aplastic anaemia. The age ranged from early childhood to young adulthood. We excluded studies on participants with secondary aplastic anaemia.
INTERVENTIONS
We included allogeneic haematopoietic stem cell transplantation as the test intervention harvested from any source of matched sibling donor and serving as a first-line therapy. We included immunosuppressive therapy as comparator with either antithymocyte/antilymphocyte globulin or ciclosporin or a combination of the two. PRIMARY AND SECONDARY OUTCOME MEASURES PLANNED AND FINALLY MEASURED: The primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, graft-versus-host disease, no response to immunosuppressive therapy, relapse after initial successful treatment, secondary clonal disease or malignancies, health-related quality of life and performance scores.
RESULTS
We identified three prospective non-randomised controlled trials with a study design that was consistent with the principle of 'Mendelian randomisation' in allocating patients to treatment groups. All studies had a high risk of bias due to the study design and were conducted more than 15 years. The pooled HR for overall mortality for the donor group versus the no donor group was 0.95 (95% CI 0.43 to 2.12, p=0.90).
CONCLUSIONS
There are insufficient and biased data that do not allow any firm conclusions to be made about the comparative effectiveness of first-line allogeneic haematopoietic stem cell transplantation of HLA-matched sibling donors and first-line immunosuppressive therapy of patients with acquired severe aplastic anaemia.
Topics: Adolescent; Anemia, Aplastic; Child; Child, Preschool; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant; Severity of Illness Index; Siblings; Tissue Donors; Treatment Outcome; Young Adult
PubMed: 25031191
DOI: 10.1136/bmjopen-2014-005039 -
Clinical & Translational Oncology :... Jan 2006Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including... (Review)
Review
INTRODUCTION
Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including solid and haematological malignancies or aplastic anaemia.
OBJECTIVE
This review was aimed at evaluating overall NEC mortality rate, describing clinical diagnostic findings and therapeutical interventions reported in the literature and generating a hypothesis regarding factors influencing mortality and surgical intervention.
MATERIALS AND METHODS
An advanced search was made in Medline, Embase, Lilacs and Google. Additional strategies included manual search of specific journals. Reports were considered if they described case definition, inclusion and exclusion criteria.
RESULTS
275 cases were selected; 109 were from individual data and 40 from grouped data. Comparing data between case reports and case series revealed no significant differences related to mortality, surgical intervention, sex or age. Higher mortality (chi2 = 7.51 p = 0.006) was found in women (50%) compared to men (28%). No significant difference was found between antibiotic combinations and mortality (chi(2) = 12.85 df 13 p = 0.45). Mortality (chi2 = 3.89 df 1, p = 0.049), surgical intervention (chi2 = 7.64 df 1, p = 0.006) and duration of diarrhoea (chi2 = 4.71 df 1, p = 0.043) were significantly different in 26.4% of individuals using antifungal agents; death occurred in 81% of patients! who did not receive such medication compared to 19% individuals reported as being treated with antifungal agents.
CONCLUSION
The current evidence suggests that antifungal agents should be used early in patients suffering from NEC. However, this hypothesis must be evaluated in multi-centric, randomised controlled trials.
Topics: Adult; Anti-Bacterial Agents; Antineoplastic Agents; Case Management; Combined Modality Therapy; Enterocolitis, Neutropenic; Female; Humans; Male; Middle Aged; Mucositis; Neoplasms; Neutropenia; Publishing; Radiography; Sex Factors; Treatment Outcome; Vomiting
PubMed: 16632437
DOI: 10.1007/s12094-006-0092-y -
Frontiers in Neurology 2020This study reported two cases of intracranial thrombotic events of aplastic anemia (AA) under therapy with cyclosporine-A (CsA) and reviewed both drug-induced cerebral...
This study reported two cases of intracranial thrombotic events of aplastic anemia (AA) under therapy with cyclosporine-A (CsA) and reviewed both drug-induced cerebral venous thrombosis (CVT) and CsA-related thrombotic events systematically. We searched PubMed Central (PMC) and EMBASE up to Sep 2019 for publications on drug-induced CVT and Cs-A-induced thrombotic events. Medical subject headings and Emtree headings were used with the following keywords: "cyclosporine-A" and "cerebral venous thrombosis OR cerebral vein thrombosis" and "stroke OR Brain Ischemia OR Brain Infarction OR cerebral infarction OR intracerebral hemorrhage OR intracranial hemorrhage." We found that CsA might be a significant risk factor in inducing not only CVT but also cerebral arterial thrombosis in patients with AA.
PubMed: 33643175
DOI: 10.3389/fneur.2020.563037 -
International Journal of Pediatric... Nov 2016Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and... (Review)
Review
BACKGROUND
Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review.
METHODS
We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included. Demographics, treatment and outcomes were analyzed using R Gui statistical software.
RESULTS
Twelve studies met inclusion criteria (103 patients). There was male preponderance of 48.5% with median age of 11 years old. Majority of patients had underlying leukemia (44.6%). Aspergillus was the predominant organism (47%). Isolated nasal findings occurred in 14% of patients and nasal findings occurred in 49% overall. Absolute neutrophil count (ANC) of immunocompromised patients was below 600 in most patients (99%). Average and median length of neutropenia was 2 weeks. All patients were prescribed amphoterocin with 50% as single medicinal therapy. Surgery occurred in 82.8% of cases. The mortality rate was 46%. Univariate analysis identified presenting with facial pain as a negative predictor of overall mortality (OR 0.296, 95% CI: 0.104-0.843, p < 0.05).
CONCLUSION
Mortality remains high in pediatric patients with IFS. An ANC of <600 occurred in the majority of immunocompromised patients at a duration of 2 weeks. Presenting with facial pain was a negative predictor of mortality. Many studies label this condition as invasive fungal sinusitis; however, approximately one seventh presented with only nasal findings and half overall had nasal involvement.
Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Burkitt Lymphoma; Candidiasis, Invasive; Child; Facial Pain; Female; Fusariosis; Humans; Immunocompromised Host; Leukemia; Male; Mucormycosis; Mycoses; Neutropenia; Otorhinolaryngologic Surgical Procedures; Prognosis; Retrospective Studies; Sinusitis
PubMed: 27729140
DOI: 10.1016/j.ijporl.2016.09.019 -
The Cochrane Database of Systematic... Oct 2015Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a... (Comparative Study)
Comparative Study Review
Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders.
BACKGROUND
Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear.
OBJECTIVES
To assess the efficacy and safety of a restrictive versus liberal red blood cell transfusion strategy for patients with myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th May 2015.
SELECTION CRITERIA
RCTs including patients with long-term bone marrow failure disorders that require allogeneic blood transfusion, who are not being actively treated with a haematopoietic stem cell transplant, or intensive chemotherapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane review methodology. One author initially screened all references, and excluded any that were clearly irrelevant or duplicates. Two authors then independently screened all abstracts of articles, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant articles for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool.
MAIN RESULTS
We included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS.The quality of the evidence was very low across different outcomes according to GRADE methodology.The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above).
AUTHORS' CONCLUSIONS
This review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population.
Topics: Anemia, Aplastic; Anemia, Refractory; Bone Marrow Diseases; Clinical Protocols; Erythrocyte Transfusion; Humans; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Randomized Controlled Trials as Topic
PubMed: 26436602
DOI: 10.1002/14651858.CD011577.pub2 -
Annals of Hematology May 2020Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital...
Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital abnormalities, bone marrow failure (BMF), and high incidences of malignancies. FA mosaicism arises from reversion or other compensatory mutations in hematopoietic cells and may be associated with BMF reversal and decreased blood cell sensitivity to DNA-damaging agents (clastogens); this sensitivity is a phenotypic and diagnostic hallmark of FA. Uncertainty regarding the clinical significance of FA mosaicism persists; in some cases, patients have survived multiple decades without BMF or hematologic malignancy, and in others hematologic failure occurred despite the presence of clastogen-resistant cell populations. Assessment of mosaicism is further complicated because clinical evaluation is frequently based on clastogen resistance in lymphocytes, which may arise from reversion events both in lymphoid-specific lineages and in more pluripotent hematopoietic stem/progenitor cells (HSPCs). In this review, we describe diagnostic methods and outcomes in published mosaicism series, including the substantial intervals (1-6 years) over which blood counts normalized, and the relatively favorable clinical course in cases where clastogen resistance was demonstrated in bone marrow progenitors. We also analyzed published FA mosaic cases with emphasis on long-term clinical outcomes when blood count normalization was identified. Blood count normalization in FA mosaicism likely arises from reversion events in long-term primitive HSPCs and is associated with low incidences of BMF or hematologic malignancy. These observations have ramifications for current investigational therapeutic programs in FA intended to enable gene correction in long-term repopulating HSPCs.
Topics: Bone Marrow Cells; Fanconi Anemia; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Mosaicism
PubMed: 32065290
DOI: 10.1007/s00277-020-03954-2 -
ANZ Journal of Surgery Dec 2018Chloramphenicol ointment is often used in plastic and dermatologic surgery as a topical antibiotic for surgical wounds, but evidence regarding its efficacy and side...
BACKGROUND
Chloramphenicol ointment is often used in plastic and dermatologic surgery as a topical antibiotic for surgical wounds, but evidence regarding its efficacy and side effects is lacking. In addition, anecdotal fear of aplastic anaemia exists from the oral use of this drug. We performed a systematic review of the literature to assess the efficacy and side effect profile of topical chloramphenicol ointment on non-ocular surgical wounds.
METHODS
A systematic search of MEDLINE, EMBASE and the Cochrane Library from inception until 4 September 2017 was undertaken. Clinical studies of topical chloramphenicol ointment use on surgical wounds were included. Studies looking only at ocular use or those not available in full text or English were excluded. The review was conducted adhering to PRISMA guidelines.
RESULTS
After full-text review, five articles were included. Two were randomized controlled trials, one was retrospective case control and two were case studies. There was evidence that chloramphenicol ointment use on surgical wounds produced a non-statistically significant reduction in infection rates. Delayed hypersensitivity and acute oesophagitis were noted as potential side effects of non-ocular topical use. Aplastic anaemia was not reported.
CONCLUSION
There is a paucity of clinical data regarding the use of topical chloramphenicol ointment on surgical wounds. Further randomized controlled trials may be beneficial in order to support or refute its use in this setting.
Topics: Administration, Topical; Anti-Bacterial Agents; Chloramphenicol; Dermatologic Surgical Procedures; Humans; Ointments; Surgical Wound; Surgical Wound Infection; Treatment Outcome; Wound Healing
PubMed: 29573103
DOI: 10.1111/ans.14465 -
Frontiers in Immunology 2019Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells...
Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation.
Topics: Animals; Autoimmune Diseases; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Differentiation; Epigenesis, Genetic; Epigenomics; Humans; T-Lymphocytes, Regulatory
PubMed: 31057561
DOI: 10.3389/fimmu.2019.00856