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Haematologica Jul 2018Exosomal microRNAs modulate cancer cell metabolism and the immune response. Specific exosomal microRNAs have been reported to be reliable biomarkers of several solid and...
Exosomal microRNAs modulate cancer cell metabolism and the immune response. Specific exosomal microRNAs have been reported to be reliable biomarkers of several solid and hematologic malignancies. We examined the possible diagnostic and prognostic values of exosomal microRNAs in two human bone marrow failure diseases: aplastic anemia and myelodysplastic syndromes. After screening 372 microRNAs in a discovery set (n=42) of plasma exosome samples, we constructed a customized PCR plate, including 42 microRNAs, for validation in a larger cohort (n=99). We identified 25 differentially expressed exosomal microRNAs uniquely or frequently present in aplastic anemia and/or myelodysplastic syndromes. These microRNAs could be related to intracellular functions, such as metabolism, cell survival, and proliferation. Clinical parameters and progression-free survival were correlated to microRNA expression levels in aplastic anemia and myelodysplastic syndrome patients before and after six months of immunosuppressive therapy. One microRNA, mir-126-5p, was negatively correlated with a response to therapy in aplastic anemia: patients with higher relative expression of miR-126-5p at diagnosis had the shortest progression-free survival compared to those with lower or normal levels. Our findings suggest utility of exosomal microRNAs in the differential diagnosis of bone marrow failure syndromes. (Registered at ).
Topics: Anemia, Aplastic; Biomarkers; Case-Control Studies; Circulating MicroRNA; Computational Biology; Exosomes; Gene Expression Profiling; Humans; MicroRNAs; Myelodysplastic Syndromes; Prognosis; Reproducibility of Results
PubMed: 29674506
DOI: 10.3324/haematol.2017.182824 -
Blood Aug 1972
Topics: Androgens; Anemia, Aplastic; Blood Transfusion; Bone Marrow Transplantation; Chloramphenicol; Hematopoiesis; Hematopoietic Stem Cells; Hemoglobinuria, Paroxysmal; Histocompatibility Testing; Humans; Leukemia; Precancerous Conditions; Radiation Effects
PubMed: 4557987
DOI: No ID Found -
Hematology. American Society of... Dec 2019Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched... (Review)
Review
Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched unrelated donor, an unrelated donor for umbilical cord blood transplantation (UCBT), or a haploidentical donor depends not only on the availability of the donor but also on patient-, disease-, and center-related factors. This paper summarizes the recent criteria in the selection of cord blood unit, including the cell dose requirement and the HLA typing for the optimal donor choice. The main strategies to optimize the results of UCBT, the conditioning regimens, and the use of antithymocyte globulin and the other platforms of graft-versus-host disease prophylaxis are discussed. The paper describes the results of UCBT in children and adults with malignant and nonmalignant diseases and the comparative analysis with other donor type and stem cell sources. Emerging strategies, focusing on the different platforms of ex vivo expansion and the new applications using cord blood stem cell, are also examined.
Topics: Adolescent; Adult; Anemia, Aplastic; Cord Blood Stem Cell Transplantation; Donor Selection; Female; Histocompatibility Testing; Humans; Leukemia, Myeloid, Acute; Male; Transplantation Conditioning
PubMed: 31808851
DOI: 10.1182/hematology.2019000056 -
Best Practice & Research. Clinical... Dec 2023The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or... (Review)
Review
The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or syndromic multisystem disease. Patients with BMFS frequently experience poor outcomes, and improved treatment strategies are needed. Collation of clinical characteristics and patient outcomes in a national disease-specific registry represents a powerful tool to identify areas of need and support clinical and research collaboration. Novel treatment strategies such as gene therapy, particularly in rare diseases, will depend on the ability to identify eligible patients alongside the molecular genetic features of their disease that may be amenable to novel therapy. The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry (AAR) aims to improve outcomes for all paediatric and adult patients with BMFS in Australia by describing the demographics, treatments (including supportive care) and outcomes, and serving as a resource for research and practice improvement.
Topics: Adult; Humans; Child; Anemia, Aplastic; Bone Marrow Diseases; Australia; Bone Marrow Failure Disorders; Syndrome; Registries
PubMed: 38092475
DOI: 10.1016/j.beha.2023.101516 -
Best Practice & Research. Clinical... Jun 2021Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune... (Review)
Review
Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune aplastic anemia, the commonest BMF, is a diagnosis of exclusion. In this review, we discuss a general approach to the evaluation of BMF, focusing on clinical presentations particular to immune and various constitutional disorders as well as the interpretation of bone marrow histology, flow cytometry, and karyotyping. Additionally, we examine the role of specialized testing in both immune and inherited BMF, and discuss genetic testing, both its role in patient evaluation and interpretation of results.
Topics: Anemia, Aplastic; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Genetic Testing; Hematology; Humans
PubMed: 34404527
DOI: 10.1016/j.beha.2021.101275 -
Indian Pediatrics Jun 2022In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability...
JUSTIFICATION
In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT).
PROCESS
Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts.
OBJECTIVE
To facilitate appropriate management of children with acquired aplastic anemia.
RECOMMENDATIONS
Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophos-phamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.
Topics: Anemia, Aplastic; Child; Cyclosporins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Pediatrics
PubMed: 35105820
DOI: No ID Found -
Current Opinion in Hematology Nov 2016There has been a steady improvement in outcomes with allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA), because of progress in optimization... (Review)
Review
PURPOSE OF REVIEW
There has been a steady improvement in outcomes with allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA), because of progress in optimization of the conditioning regimens, donor hematopoietic cell source, and supportive care. Here, we review recently published data that highlight the improvements and current issues in the treatment of SAA.
RECENT FINDINGS
Approximately one-third of aplastic anemia patients treated with immune suppressive therapy (IST) have acquired mutations in myeloid cancer candidate genes. Because of the greater probability for eventual failure of IST, human leukocyte antigen (HLA)-matched sibling donor BMT is the first-line of treatment for SAA. HLA-matched unrelated donor (URD) BMT is generally recommended for patients who have failed IST. However, in younger patients for whom a 10/10-HLA-allele matched URD can be rapidly identified, there is a strong rationale to proceed with URD BMT as first-line therapy. HLA-haploidentical BMT using posttransplant cyclophosphamide conditioning regimens is now a reasonable second-line treatment for patients who failed IST.
SUMMARY
Improved outcomes have led to an increased first-line role of BMT for treatment of SAA. The optimal cell source from an HLA-matched donor is bone marrow. Additional studies are needed to determine the optimal conditioning regimen for HLA-haploidentical donors.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Chromosome Aberrations; Genetic Predisposition to Disease; HLA Antigens; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Mutation; Peptides; Siblings; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 27607445
DOI: 10.1097/MOH.0000000000000281 -
Haematologica Jan 2007
Topics: Adolescent; Adult; Anemia, Aplastic; Bone Marrow; Child; Clinical Trials as Topic; Humans; Immunosuppressive Agents; Middle Aged; Recurrence; Treatment Outcome
PubMed: 17229628
DOI: 10.3324/haematol.11107 -
Hematology/oncology Clinics of North... Aug 2018Hematopoietic stem cell transplantation (bone marrow transplantation [BMT]) is the only curative treatment of severe aplastic anemia. BMT from an human leukocyte antigen... (Review)
Review
Hematopoietic stem cell transplantation (bone marrow transplantation [BMT]) is the only curative treatment of severe aplastic anemia. BMT from an human leukocyte antigen (HLA)-matched sibling donor is the standard of care for young patients; immunosuppressive therapy is used for older patients or those lacking matched sibling donors. Patients with refractory or relapsed disease are increasingly treated with HLA haploidentical BMT. Historically, haploidentical BMT led to high rates of graft rejection and graft-versus-host disease. High-dose post transplant cyclophosphamide, which mitigates the risk of graft-versus-host disease, is a major advance. This article provides an overview of the haploidentical BMT approach in severe aplastic anemia.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Graft vs Host Disease; Humans; Immunosuppression Therapy; Siblings; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 30047416
DOI: 10.1016/j.hoc.2018.04.001 -
The Korean Journal of Internal Medicine Nov 2014Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from... (Review)
Review
Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Topics: Anemia, Aplastic; Humans; Immunosuppressive Agents; Iron Chelating Agents; Risk Factors; Stem Cell Transplantation; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 25378968
DOI: 10.3904/kjim.2014.29.6.713