Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
Because of its potent immunosuppressive yet stem cell-sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).
由于其强大的免疫抑制作用和干细胞保留活性，高剂量环磷酰胺被测试作为骨髓移植（alloBMT）后同种异体骨髓移植（GVHD）的唯一预防药物。我们治疗了 117 例（中位年龄 50 岁；范围 21-66 岁）患有晚期血液系统恶性肿瘤的患者；78 例有人类白细胞抗原（HLA）匹配的相关供体，39 例有 HLA 匹配的无关供体。所有患者均接受常规骨髓清除术，用白消安/环磷酰胺（BuCy）和 T 细胞丰富的骨髓进行预处理，然后在移植后第 3 和第 4 天接受 50mg/kg/d 的环磷酰胺治疗。所有患者的急性 II 至 IV 级和 III 至 IV 级 GVHD 的发生率分别为 43%和 10%。移植后第 100 天和 2 年的非复发死亡率分别为 9%和 17%。所有患者移植后 2 年的总生存率和无事件生存率分别为 55%和 39%，缓解期患者分别为 63%和 54%。在存活患者的中位随访 26.3 个月时，慢性 GVHD 的累积发生率为 10%。这些结果表明，高剂量移植后环磷酰胺是 BuCy 条件下和 HLA 匹配 BMT 后急性和慢性 GVHD 的有效单一预防药物（临床试验.gov 编号：NCT00134017）。
