Zülfikar B
Institute of Oncology, University of Istanbul, The Hemophilia Society of Turkey, Istanbul, Turkey.
Haemophilia. 2002 Sep;8(5):698-702. doi: 10.1046/j.1365-2516.2002.00660.x.
Acute leukaemia is the commonest form of malignancy in childhood. The coincidental development of leukaemia in children or adults with haemophilia is extremely rare, although cases of leukaemia and other malignancies have been reported previously in HIV-positive subjects. Of a total of 440 people with haemophilia registered with our society, two were diagnosed with acute leukaemia last year. The development of leukaemia in a subject with haemophilia has previously been reported from our country in 1985, but the negative HIV status of these recent cases is very interesting. The first case involved a 14-year-old boy with moderate haemophilia A, who developed acute lymphoblastic leukaemia (ALL) [French-American-British (FAB) classification L2]. The second subject was a 16-year-old boy who had moderately severe haemophilia A with no previous family history, and developed acute nonlymphocytic (myelomonocytic) leukaemia (FAB-M4). Both patients received conventional chemotherapy and this report discusses the potential problems in management of such cases, including diagnosis and administration of chemotherapy in subjects with a pre-existing haemorrhagic disorder. Extensive cutaneous and mucosal bleeding, as well as bleeds in joints previously affected by haemarthrosis and alterations of haematological values were all initially suggestive of the development of inhibitors against factor VIII, but the appearance of blasts in the peripheral blood and bone marrow led to the definitive diagnosis. The risk of bleeding, due to the combination of both leukaemia and the consequences of the chemotherapy, was overcome by the administration of coagulation factor concentrates (daily initially followed by prophylactic doses after successful induction of remission in both patients). The young patient with ALL is now receiving the maintenance phase of the Children's Cancer Study Group 1961 protocol and is in the 15th month of follow-up, without any complications. The other case relapsed in the seventh month, developing enterobacter sepsis, and died. An important lesson to be learnt from these cases is that the possible diagnosis of leukaemia should not be overlooked in a patient with haemophilia and severe haemorrhagic problems, if the first-line differential diagnosis of inhibitor development against factor VIII (or IX) has been excluded.
急性白血病是儿童期最常见的恶性肿瘤形式。血友病患儿或成人同时并发白血病极为罕见，尽管此前曾有报告称HIV阳性者患白血病及其他恶性肿瘤的病例。在我们协会登记的440名血友病患者中，去年有两人被诊断为急性白血病。1985年我国曾报告过血友病患者发生白血病的情况，但最近这两例患者HIV检测呈阴性，这一点很有意思。第一例是一名14岁的中度甲型血友病男孩，患急性淋巴细胞白血病（ALL）[法美英（FAB）分类L2]。第二例是一名16岁男孩，患有中度重型甲型血友病，无前家族病史，患急性非淋巴细胞（髓单核细胞）白血病（FAB-M4）。两名患者均接受了常规化疗，本报告讨论了此类病例管理中的潜在问题，包括对已有出血性疾病患者的诊断和化疗给药。广泛的皮肤和黏膜出血，以及先前受血友病影响的关节出血和血液学指标改变，最初均提示可能出现了抗凝血因子VIII的抑制物，但外周血和骨髓中出现原始细胞导致了最终诊断。由于白血病和化疗的双重影响导致出血风险增加，通过给予凝血因子浓缩物得以克服（最初每日给药，两名患者诱导缓解成功后改为预防性剂量）。患ALL的年轻患者目前正在接受儿童癌症研究组1961方案的维持治疗阶段，随访已达15个月，无任何并发症。另一例在第七个月复发，并发肠杆菌败血症，死亡。从这些病例中吸取的一个重要教训是，如果已排除针对凝血因子VIII（或IX）的抑制物形成这一一线鉴别诊断，那么对于患有血友病且有严重出血问题的患者，不应忽视白血病的可能诊断。
