High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up
ABSTRACT Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatment-naive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for severe aplastic anemia. Large randomized controlled trials will be necessary to establish how results of high-dose cyclophosphamide compare with either bone marrow transplantation or standard immunosuppressive regimens, such as antithymocyte globulin and cyclosporine.
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ABSTRACT: Aplastic anaemia (AA) is a rare heterogeneous condition in children. 15-20% of cases are constitutional and correct diagnosis of these inherited causes of AA is important for appropriate management. For idiopathic severe aplastic anaemia, a matched sibling donor (MSD) haematopoietic stem cell transplant (HSCT) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. IST with horse anti-thymocyte globulin (ATG) is superior to rabbit ATG and has good long-term results. In contrast, IST with rabbit ATG has an overall response of only 30-40%. Due to improvements in outcome over the last two decades in matched unrelated donor (MUD) HSCT, results are now similar to that of MSD HSCT. The decision to proceed with IST with ATG or MUD HSCT will depend on the likelihood of finding a MUD and the differing risks and benefits that each therapy provides.British Journal of Haematology 02/2012; 157(1). DOI:10.1111/j.1365-2141.2012.09058.x · 4.96 Impact Factor
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ABSTRACT: Immunosuppression is a key treatment strategy for aplastic anaemia (AA) and the related immune-mediated bone marrow failure syndromes (BMFS). For the last 20 years the standard immunosuppressive regimen for AA patients has been anti-thymocyte globulin (ATG) plus ciclosporin A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after immunosuppressive therapy remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. This article reviews the state of the art of current immunosuppressive therapies for AA, focusing on open questions linked to standard immunosuppressive treatment, and on experimental immunosuppressive strategies which could lead to future improvement of current treatments. Specific immunosuppressive strategies employed for other BMFS, such as lineage-restricted marrow failures, myelodysplastic syndromes and large granular lymphocyte leukaemia-associated cytopenias, are also briefly discussed.British Journal of Haematology 01/2011; 152(2):127-40. DOI:10.1111/j.1365-2141.2010.08439.x · 4.96 Impact Factor
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ABSTRACT: Acquired aplastic anemia (AA) is the typical bone marrow failure syndrome characterized by an empty bone marrow; an immune-mediated pathophysiology has been demonstrated by experimental works as well as by clinical observations. Immunusuppressive therapy (IST) is a key treatment strategy for aplastic anemia; since 20 years the standard IST for AA patients has been anti-thymocyte globuline (ATG) plus cyclosporine A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. Here we review the state of the art of IST for AA in 2010, focusing on possible strategies to improve current treatments. We also discuss very recent data which question the equality of different ATG preparations, leading to a possible reconsideration of the current standards of care for AA patients.Pediatric reports 06/2011; 3 Suppl 2(Suppl 2):e7. DOI:10.4081/pr.2011.s2.e7