[Intervention Protocol]First-line stem cell transplantation from related donors compared to immunosuppressive treatment for acquired severe aplastic anaemia Eva-Brigitta
A B S T R A C TThis is the protocol for a review and there is no abstract. The objectives are as follows:To evaluate the effectiveness of stem cell transplantation from related donors compared to immunosuppression in the first-line treatment of (very) severe aplastic anaemia and to assess the frequency and severity of undesired adverse effects.
B A C K G R O U N D
Description of the conditionAcquired aplastic anaemia is a rare but life-threatening disease characterised by a failure of haemopoietic stem cells, resulting in bone-marrow aplasia and pancytopenia. Although there are a number of inherited forms, often associated with other symptoms (Killick 2000), most cases are acquired forms. The incidence is given at around 2 cases per one million inhabitants in Europe and North America, but is usually higher in Asia and can be as much as 15 cases per one million (Jaime-Perez 2005). Most often the disease presents in 15 to 25-year-olds, while there is a second peak in people older than 60 years (Brodsky 2005). In spite of the various causes believed to lead to aplastic anaemia -like certain drugs, chemical agents, radiation, different bacteria and viruses as well as non-viral hepatitis and pregnancy -most cases remain idiopathic (Killick 2000, Bacigalupo 2000. However, for all acquired forms, the pathophysiology is probably similar: an autoimmune destruction of haemopoietic stem cells effected by autoreactive T cells and autoantibodies against proteins expressed on haemopoietic cells (Young 2002, Brodsky 2005. Patients suffering from aplastic anaemia commonly present with signs and symptoms of thrombocytopenia, leading to various forms of bruising and bleeding. Other manifestations of the disease are anaemia leading to weakness, fatigue and shortness of breath, as well as leukocytopenia. As the disease progresses, haemorrhage and multiple severe infections due to neutropenia become more prominent and are the most common cause of death (Brodsky 2005, Ljungman 2000. Diagnosis is established by full blood count and bone marrow biopsy and aspirate, all of which also serve to exclude other possible causes of aplasia and/or peripheral pancytopenia (Marsh 2003). The following criteria determine the presence of aplastic anaemia (Hohloch 2003, Marín-Fernandez 2000:• hypoplastic bone marrow • two out of the following three: • neutrophil count < 1x10 9 /l, severe aplastic anaemia: < 0,5x10 9 /l • thrombocyte count < 50x10 9 /l, severe aplastic anaemia: < 20x10 9 /l• reticulocyte count < 40x10 9 /l, severe aplastic anaemia: < 20x10 9 /l or less than 1% These are also known as the Camitta criteria as they have been first described by B. M. Camitta in 1975 (Camitta 1975 and little modified since then. Special caution must be applied to differentiate aplastic anaemia from other forms of haematologic aplasia or myelodysplastic syndromes (Hohloch 2003).
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