Department of Haematology, Christian Medical College, Vellore, India.
Department of Haematology, Christian Medical College, Vellore, India.
Biol Blood Marrow Transplant. 2018 Mar;24(3):494-500. doi: 10.1016/j.bbmt.2017.10.034. Epub 2017 Oct 31.
High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m [MTX15] and 10 mg/m [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.
在异基因造血细胞移植（HSCT）后使用高剂量环磷酰胺（PTCY）已被证明可有效预防 HLA 匹配骨髓移植后移植物抗宿主病（GVHD）。我们进行了一项 II 期研究，在接受粒细胞集落刺激因子动员的外周血干细胞（PBSC）移植后，在 HLA 匹配的相关供体中，使用氟达拉滨、环磷酰胺和单次全身照射进行预处理的严重再生障碍性贫血（SAA）患者中，在 HSCT 后第 3 和第 4 天以 50mg/kg 的剂量静脉内给予 PTCY 作为唯一的 GVHD 预防药物。30 名中位年龄为 29 岁（范围 16 至 49 岁）的患者入组本研究。27 名患者（90%）在 HSCT 后中位 16 天（范围 12 至 21 天）时出现移植物嵌合。没有患者发生肝静脉阻塞性疾病或出血性膀胱炎。22%的患者发生 II 至 IV 级急性 GVHD，11.1%的患者发生 III 至 IV 级 GVHD。2 年慢性 GVHD 的累积发生率为 22.7%。14 名患者（46.6%）在接受 PTCY 后无需进一步接受免疫抑制治疗。与接受环孢素和甲氨蝶呤（MTX；15mg/m [MTX15] 和 10mg/m [MTX10]）的 2 个历史队列（每组 30 例）相比，使用 PTCY 的 II 至 IV 级急性 GVHD 的发生率虽然没有显著降低，但有所降低（PTCY，22.2%，vs MTX15，37.1%，vs MTX10，53.8%；P=0.056），而慢性 GVHD 的发生率显著降低（PTCY，22.7%，vs MTX15，63.6%，vs MTX10，76.2%；P=0.013）。与环孢素和 MTX 相比，使用 PTCY 时病毒感染（包括巨细胞病毒）明显更高（60% vs 环孢素和 MTX；MTX15，23.3%，vs MTX10，33.3%；P=0.008）。3 组之间的总生存率相似。我们得出结论，在使用 HLA 匹配供体的 PBSC 移植治疗 SAA 的患者中，PTCY 作为唯一的 GVHD 预防药物与急性和慢性 GVHD 的低发生率相关。本试验在 CTRI/2010/091/001480 注册。
