High-dose cyclophosphamide for severe aplastic anemia: Long-term follow-up

Division of Hematology,Department of Medicine, Johns Hopkins University School ofMedicine, 720 Rutland Ave, Ross Bldg, Rm 1025, Baltimore, MD 21205, USA.
Blood (Impact Factor: 10.45). 12/2009; 115(11):2136-41. DOI: 10.1182/blood-2009-06-225375
Source: PubMed


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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    • "For those children lacking a suitable unrelated donor (10/10 or 9/10) and failing IST, possible options include a second course of ATG, an alternative IST or umbilical cord/ haploidentical HSCT. Alternative IST options include high dose cyclophosphamide (Brodsky et al, 2010) or alemtuzumab (Risitano et al, 2010). However further studies are required in children to determine their long-term efficacy and optimal dosing. "
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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.
    Preview · Article · Feb 2012 · British Journal of Haematology
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    • "High-dose CTX (50 mg/kg intravenously on 4 consecutive days) was mainly tested at the Johns Hopkins University; the initial results were excellent, with a response rate of about 70% (even if the time-to-response appeared delayed in comparison to that expected with ATG).39 This single-center experience continues to show interesting results, with the most recent follow up reporting 44 naïve AA patients showing response rate, overall survival and event free survival of 88%, 71% (the majority complete) and 58%, respectively.40 However, most investigators do not consider CTX as a feasible treatment option for AA patients, based on the results of the randomized study versus ATG + CyA conducted at NIH. "
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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.
    Full-text · Article · Jun 2011 · Pediatric reports
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    • "In the latter study, even the initial observation that CTX may reduce the risk of MDS/AML development was not confirmed (Tisdale et al, 2002). Based on these results, CTX is not considered as a feasible IST by most investigators; however, the on-going single-centre experience at John Hopkins continues to show excellent results, even at a very long follow up (Brodsky et al, 2010). Recent data from China, showing the feasibility and the efficacy of a low-dose oral CTX, have renewed the interest on CTX as possible alternative immunosuppressive agent for AA (unpublished observations). "
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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.
    Preview · Article · Jan 2011 · British Journal of Haematology
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