Allogeneic hematopoietic cell transplantation (HCT) has been shown to restore normal hematopoiesis in patients with Fanconi anemia (FA), with excellent results in matched related donor HCT. Outcomes of alternative donor HCT are less favorable, however. In patients without FA, several reports have documented stable engraftment and/or a low risk of graft-versus-host disease (GVHD) using unmanipulated HLA-mismatched related donors and post-HCT cyclophosphamide (PT-CY) for GVHD prophylaxis. Data on the use of this approach in patients with FA are scarce, and thus we launched a study of HLA-mismatched related donor HCT in these patient. Here we report our findings in 19 patients. The conditioning was fludarabine 30 mg/m2/day for 5 days, antithymocyte globulin 5 mg/kg/day for 4 days, and total body irradiation (total dose, 200 cGy). GVHD prophylaxis was cyclosporine and mycophenolate and reduced doses of PT-CY, 25 mg/kg, on days +3 and +5. All patients exhibited absolute neutrophil count recovery. Grade III-IV acute GVHD occurred in 3 patients, and chronic GVHD occurred in 1 patient. At a mean follow-up of 38.3 ± 5.8 months, the 5-year probability of overall survival for our patients was 89.2% ± 7.2%. The regimen was well tolerated; hemorrhagic cystitis occurred in 7 patients, and severe mucositis occurred in 5 patients. There were 2 deaths; the primary cause of death was severe GVHD in 1 patient and leukemia recurrence in the other. We conclude that in patients with FA lacking a matched related donor, the use of mismatched related HCT with low-dose PT-CY is a viable option; it is well tolerated, with a high rate of engraftment and an acceptable incidence of GVHD.

中文翻译：

---

使用减少剂量的环磷酰胺移植后进行T细胞补充性错配相关供体造血细胞移植的范可尼贫血患者的成功结果。

异基因造血细胞移植（HCT）已显示可恢复Fanconi贫血（FA）患者的正常造血功能，在相配的相关供体HCT中取得了优异的结果。但是，替代供体HCT的结果较差。在没有FA的患者中，有几篇报道记录了使用未经操纵的HLA不匹配的相关供体和HCT后的环磷酰胺（PT-CY）预防GVHD的稳定植入和/或低风险的移植物抗宿主病（GVHD）。关于在FA患者中使用这种方法的数据很少，因此我们在这些患者中开展了HLA不匹配相关供体HCT的研究。在这里，我们报告19位患者的发现。条件是氟达拉滨30 mg / m2 /天，持续5天，抗胸腺细胞球蛋白5 mg / kg /天，持续4天，以及全身照射（总剂量为200 cGy）。GVHD的预防是环孢素和霉酚酸酯，在+3天和+5天时降低PT-CY的剂量25 mg / kg。所有患者均表现出绝对中性粒细胞计数恢复。III-IV级急性GVHD发生在3例患者中，而慢性GVHD发生在1例患者中。平均随访时间为38.3±5.8个月，我们患者的5年总生存率为89.2％±7.2％。该方案耐受性良好。出血性膀胱炎发生7例，重度粘膜炎发生5例。有2人死亡。死亡的主要原因是1例患者严重GVHD，另一例患者白血病复发。我们得出的结论是，在FA患者中缺少匹配的相关供体的情况下，将失配的相关HCT与低剂量PT-CY结合使用是一种可行的选择。它具有良好的耐受性，较高的植入率和可接受的GVHD发生率。