Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children

Department of Paediatric Haematology, Great Ormond Street Hospital, London, UK.
Pediatric Blood & Cancer (Impact Factor: 2.56). 04/2008; 50(4):831-2. DOI: 10.1002/pbc.21425
Source: PubMed

ABSTRACT Hepatic veno-occlusive disease (VOD) is a common (10-50%) and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We carried out a study to assess whether the use of prophylactic defibrotide in paediatric patients undergoing HSCT results in a lower frequency or severity of hepatic VOD.
Forty-seven successive patients who underwent transplantation between April 2004 and December 2005 were given defibrotide prophylaxis and were compared with 56 historical controls transplanted between November 2001 and April 2004. No serious side effects were reported. High risk patients in the control group received ursodeoxycholic acid and tinzaparin as VOD prophylaxis. The groups were matched for sex, age, type of transplant and risk.
In the defibrotide group, four patients developed clinical VOD (Seattle criteria) although two had liver biopsies which showed graft versus host disease (GvHD). Defibrotide dose was increased and symptoms resolved within 14 days. Of the control group four patients had VOD. Two of these patients had reversed hepatic vein flow and died 30 days post-transplant, partly due to VOD. VOD was associated with busulfan conditioning (P = 0.001) and not with age, sex, type of transplant, GvHD, abnormal liver function prior to transplant or type of antifungal prophylaxis.
VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting.

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    ABSTRACT: Background: Hepatic veno-occlusive disease (VOD) has been reported at a rate up to 50% following intensive conditioning regimens used in allogeneic hematopoietic stem cell transplantation (AHSCT). Studies on the prophylactic effect of defibrotide to prevent hepatic VOD in adults are rare.
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    ABSTRACT: Erişkinlerden farklı olarak çocuklarda hematopo-etik kök hücre transplantasyonu malign hasta-lıklar yanında birçok malign olmayan doğuştan kazanılmış hastalıkta tedavi edici bir yöntem ola-rak kullanılmaktadır. Çocuklarda 1968 yılında ilk başarılı allojenik HKHT bildirilmesinden sonra HLA gruplarının tanımlanması ve HLA uyumlu vericilerden nakillerin başlaması başarı oranını artırmıştır. Akraba dışı vericiler ve kordon kanla-rından yapılan nakillerin artması ile HKHT tüm dünyada yaygınlaşmıştır. Günümüzde çocukluk yaş grubunda hematolojik malignansiler, immun yetmezlikler, hemoglobinopatiler, kemik iliği yet-mezlikleri ve konjenital metabolik hastalıklarda hayat kurtarıcı bir tedavi yöntemi olarak kabul edilmektedir. Bu yazıda çocuklarda hematopoetik kök hücre transplantasyon endikasyonları ve transplantas-yon sonrası izlemde karşılaşılan sorunlar litera-tür gözden geçirilerek bir derleme halinde sunul-muştur. Anahtar kelimeler: Hematopetik kök hücre transplantasyonu, çocukluk çağı Hematopoetic stem cell transplantation in childhood Hematopoetic stem cell transplantation has been established as a curative therapy method in vari-ous malign and non-malign disorders in childho-od. The first successful bone marrow transplants were done in children with severe combined im-munodeficiency and Wiskott-Aldrich diseases in 1968. After the discovery of the human leukocy-te antigens (HLAs) matching between patient and donor became possible leading to increased transplantation success. After that, the number of bone marrow transplants performed worldwi-de increased substantially. The use of unrelated donors and umbilical cord blood (UCB) grafts has increased the possibilities of finding a suitable donor. Now, almost more than 20.000 transplants are performed yearly with more than modality for many diseases in children, including hematologic malignancies, immundeficiencies, hemoglobino-pathies, bone marrow failure syndromes and con-genital metabolic disorders.
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    ABSTRACT: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.
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