Gluckman E, Devergie A, Dutreix J
Br J Haematol. 1983 Jul;54(3):431-40. doi: 10.1111/j.1365-2141.1983.tb02117.x.
Fanconi anaemia, an autosomal recessive constitutional aplastic anaemia, seems to be related to a DNA repair mechanism defect. Bone marrow transplantation is sthe only treatment which can cure these patients. Previous attempts at BMT have shown an increased sensitivity to Cyclophosphamide used for the conditioning. Such a sensitivity has also been observed in vitro when Fanconi anaemia cells were incubated with alkylating agents. We have tested the in vivo radiosensitivity and cell repair after skin contact radiotherapy to calculate the irradiation dose which could be tolerated by FA patients. Eight patients have been tested and the results confirmed the suspected increased radiosensitivity in the majority of patients. Following these results, four patients were conditioned with low dose Cyclophosphamide (20 mg/kg) associated with 5 Grays thoraco-abdominal irradiation. All had a take and no major complication of the conditioning regimen. All are alive in good condition from day 51 to day 330 after transplant. Oesophagitis was one major unexpected complication. This study confirms the possibility of curing FA patients with BMT when the conditioning regimen is modified according to the pathophysiology of the disease.
范科尼贫血是一种常染色体隐性遗传性再生障碍性贫血，似乎与DNA修复机制缺陷有关。骨髓移植是唯一能治愈这些患者的治疗方法。先前的骨髓移植尝试表明，用于预处理的环磷酰胺会使其敏感性增加。当范科尼贫血细胞与烷化剂一起孵育时，在体外也观察到了这种敏感性。我们测试了皮肤接触放疗后的体内放射敏感性和细胞修复能力，以计算范科尼贫血患者能够耐受的照射剂量。对8名患者进行了测试，结果证实大多数患者存在放射敏感性增加的情况。基于这些结果，4名患者采用低剂量环磷酰胺（20mg/kg）联合5格雷胸腹部照射进行预处理。所有患者均移植成功，且预处理方案未出现重大并发症。移植后第51天至第330天，所有患者均存活且状况良好。食管炎是一种主要的意外并发症。这项研究证实，根据疾病的病理生理学调整预处理方案时，骨髓移植治愈范科尼贫血患者是有可能的。
