Kahl, C, Leisenring, W, Deeg, HJ, Chauncey, TR, Flowers, MED, Martin, PJ et al.. Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br J Haematol 130: 747-751

University of Washington Seattle, Seattle, Washington, United States
British Journal of Haematology (Impact Factor: 4.71). 10/2005; 130(5):747-51. DOI: 10.1111/j.1365-2141.2005.05667.x
Source: PubMed


A total of 81 severe aplastic anaemia patients, aged 2-63 years, received human leucocyte antigen-matched related marrow grafts after cyclophosphamide + antithymocyte globulin followed by postgrafting methotrexate + cyclosporin. Median follow-up was 9.2 years. Ninety-six per cent of patients had sustained engraftment, 24% developed acute graft-versus-host disease (GVHD), grade II in all but two patients, and 26% developed chronic GVHD; all surviving patients eventually responded to immunosuppressive therapy. Six patients developed cancer: one fatal lymphoma and five carcinomas (all five patients are now free of cancer). Survival was 88%. The regimen appeared well tolerated and effective in heavily pretreated patients with aplastic anaemia.

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Available from: Wendy Leisenring, Jan 14, 2015
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    • "In a single centre analysis, fertility was preserved in 80–90% of females and c. 60% of males with normal growth (Sanders et al, 2011). Malignancy was reported in 7–13% on long-term follow up (Kahl et al, 2005; Sanders et al, 2011). Chronic GVHD and use of total body irradiation (TBI) regimens remain the major risk factors for the development of malignancy post-MSD HSCT. "
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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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    • "Further, Walters and colleagues in their prospective clinical trial also reported a trend towards disease recurrence in patients who received chelation therapy for iron overload, implying that frequent blood transfusions may have increased the risk of graft rejection in sickle cell disease (Walters et al, 1996, 1997, 2001). Thirteen patients developed chronic GVHD with an overall rate of 22%; the rate of chronic GVHD observed here was similar to rates reported for other non-malignant diseases at similar ages (Kahl et al, 2005). Very few patients in our study experienced severe chronic GVHD, making HCT a very good treatment option for patients with sickle cell disease. "
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    ABSTRACT: We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy.
    Full-text · Article · Jun 2007 · British Journal of Haematology
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    • "Series of MSD patients conditioned with CY/ATG have either lacked multivariate analysis (Storb et al, 2001) or found age to be the only factor significantly impacting on outcome (Kahl et al, 2005). "
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    ABSTRACT: The current outlook for a child with severe idiopathic aplastic anaemia (AA) is very much better than in previous decades. In part, this may reflect better differentiation of idiopathic and inherited marrow failure. For children with idiopathic AA and a human leucocyte antigen (HLA)-matched sibling donor (MSD), allogeneic haematopoietic stem-cell transplantation (AHSCT) is the primary therapy of choice, offering long-term disease-free survival of 90%, although graft-versus-host disease remains a cause of long-term morbidity. A greater treatment challenge remains for those children without a MSD. Combination immunosuppressive therapy (IST) is associated with response rates of 70% or more. However, relapse and clonal evolution with transformation to myelodysplasia or acute myeloid leukaemia remain significant problems after IST and long-term event-free survival rates are less impressive. For children who do not have a sustained response to IST, alternate donor AHSCT should be considered. New HLA typing technologies, novel stem cell sources, reduced-intensity conditioning and graft engineering have reduced toxicity and improved the outcome after alternate donor AHSCT. Emerging therapies that capitalise on recent advances in our understanding of the pathophysiology of idiopathic AA and the immunobiology of AHSCT and IST may further improve the long-term outcome of this disease.
    Full-text · Article · Mar 2007 · British Journal of Haematology
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