Qureshi Amrana, Marshall Lynley, Lancaster Donna
Department of Paediatric Haematology, Great Ormond Street Hospital, London, UK.
Pediatr Blood Cancer. 2008 Apr;50(4):831-2. doi: 10.1002/pbc.21425.
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.
肝静脉闭塞病（VOD）是血液系统干细胞移植（HSCT）常见（发生率为10% - 50%）且严重的并发症，死亡率高达90%。我们开展了一项研究，以评估在接受HSCT的儿科患者中使用预防性去纤苷是否会降低肝VOD的发生率或严重程度。
对2004年4月至2005年12月期间连续接受移植的47例患者给予去纤苷进行预防，并与2001年11月至2004年4月期间接受移植的56例历史对照患者进行比较。未报告严重副作用。对照组中的高危患者接受熊去氧胆酸和替奈肝素作为VOD预防用药。两组在性别、年龄、移植类型和风险方面进行了匹配。
在去纤苷组中，4例患者发生了临床VOD（西雅图标准），尽管其中2例肝脏活检显示有移植物抗宿主病（GvHD）。增加去纤苷剂量后，症状在14天内得到缓解。对照组中有4例患者发生了VOD。其中2例患者肝静脉血流逆转，移植后30天死亡，部分原因是VOD。VOD与白消安预处理有关（P = 0.001），与年龄、性别、移植类型、GvHD、移植前肝功能异常或抗真菌预防用药类型无关。
去纤苷组的VOD发生率和严重程度有所降低，这表明去纤苷可能对预防和治疗VOD有效。现在需要进行足够规模的随机试验来明确去纤苷在这种情况下的作用。
