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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 -
European Journal of Haematology Sep 2014Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal disorders of haematopoietic stem cells, characterised by dysplastic haematopoiesis and... (Review)
Review
INTRODUCTION
Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal disorders of haematopoietic stem cells, characterised by dysplastic haematopoiesis and dysregulated apoptosis resulting in various degrees of cytopenia, whereas canonical cytologic, cytogenetic and histopathologic findings guiding the diagnosis MDS are widely accepted, the MDS-phenotype can be masked by coexisting/paraneoplastic immunologic disease. Autoimmune disorders have an estimated incidence of 10% among patients suffering from MDS and are causally related to increased morbidity and mortality, younger age at diagnosis and more complex genetics. Conversely, systemic inflammatory disorders may be an early manifestation of MDS, show good response to immunosuppressive therapy and frequently disappear during the course of specific haematologic therapy.
OBJECTIVE
Monocentric report on clinical phenotypes found in MDS or bone marrow failure with paraneoplastic inflammatory disease.
METHODS
Clinical case reports and systematic review about MDS pathophysiology and treatment.
RESULTS
We report eight patients diagnosed with MDS or bone marrow failure, who presented with paraneoplastic autoimmune diseases. Six of eight patients were treated with the hypomethylating agent 5-azacytidine, three of which achieved meaningful response with regard to inflammation control and haematologic recovery.
CONCLUSIONS
As paraneoplastic syndromes are often mistakenly diagnosed as idiopathic autoimmune disorders, we propose that coexistence of an underlying myelodysplastic syndrome should be considered early in the diagnostic work up. 5-Azacytidine is effective in controlling paraneoplastic inflammation.
Topics: Adult; Aged; Anemia, Aplastic; Antimetabolites, Antineoplastic; Autoimmunity; Azacitidine; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Diagnosis, Differential; Female; Hemoglobinuria, Paroxysmal; Humans; Inflammation; Male; Middle Aged; Myelodysplastic Syndromes; Paraneoplastic Syndromes; Treatment Outcome
PubMed: 24635656
DOI: 10.1111/ejh.12311