Kang Hyoung Jin, Hong Kyung Taek, Lee Ji Won, Kim Hyery, Park Kyung Duk, Shin Hee Young, Lee Soo Hyun, Yoo Keon Hee, Sung Ki Woong, Koo Hong Hoe, Lee Jae Wook, Chung Nak Gyun, Cho Bin, Kim Hack Ki, Koh Kyung Nam, Im Ho Joon, Seo Jong Jin, Jung Hyun Joo, Park Jun Eun, Lee Young Ho, Lim Young Tak, Lim Yeon Jung, Kim Sun Young, Yoo Eun Sun, Ryu Kyung Ha, Lee Jae Hee, Park Jeong-A, Park Sang Kyu, Ahn Hyo Seop
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
Biol Blood Marrow Transplant. 2016 Aug;22(8):1455-1459. doi: 10.1016/j.bbmt.2016.04.003. Epub 2016 May 8.
Hematopoietic stem cell transplantation (HSCT) is a curative therapy for severe aplastic anemia (SAA); however, the optimal conditioning regimen for HSCT with an unrelated donor has not yet been defined. A previous study using a fludarabine (FLU), cyclophosphamide (Cy), and antithymocyte globulin (ATG) conditioning regimen (study A: 50 mg/kg Cy once daily i.v. on days -9, -8, -7, and -6; 30 mg/m(2) FLU once daily i.v. on days -5, -4, -3, and -2; and 2.5 mg/kg of ATG once daily i.v. on days -3, -2, and -1) demonstrated successful engraftment (100%) but had a high treatment-related mortality rate (32.1%). Therefore, given that Cy is more toxic than FLU, we performed a new phase II prospective study with a reduced-toxicity regimen (study B: 60 mg/kg Cy once daily i.v. on days -8 and -7; 40 mg/m(2) FLU once daily i.v. on days -6, -5, -4, -3, and -2; and 2.5 mg/kg ATG once daily i.v. on 3 days). Fifty-seven patients were enrolled in studies A (n = 28) and B (n = 29), and donor type hematologic recovery was achieved in all patients in both studies. The overall survival (OS) and event-free survival (EFS) rates of patients in study B was markedly improved compared with those in study A (OS: 96.7% versus 67.9%, respectively, P = .004; EFS: 93.3% versus 64.3%, respectively, P = .008). These data show that a reduced-toxicity conditioning regimen with FLU, Cy, and ATG may be an optimal regimen for SAA patients receiving unrelated donor HSCT.
造血干细胞移植（HSCT）是治疗重型再生障碍性贫血（SAA）的一种治愈性疗法；然而，与非亲缘供者进行HSCT的最佳预处理方案尚未确定。一项先前使用氟达拉滨（FLU）、环磷酰胺（Cy）和抗胸腺细胞球蛋白（ATG）预处理方案的研究（研究A：在第-9、-8、-7和-6天静脉注射Cy，50mg/kg，每日1次；在第-5、-4、-3和-2天静脉注射FLU，30mg/m²，每日1次；在第-3、-2和-1天静脉注射ATG，2.5mg/kg，每日1次）显示植入成功（100%），但治疗相关死亡率较高（32.1%）。因此，鉴于Cy的毒性比FLU大，我们开展了一项新的II期前瞻性研究，采用低毒性方案（研究B：在第-8和-7天静脉注射Cy，60mg/kg，每日1次；在第-6、-5、-4、-3和-2天静脉注射FLU，40mg/m²，每日1次；在3天内静脉注射ATG，2.5mg/kg，每日1次）。57例患者被纳入研究A（n = 28）和研究B（n = 29），两项研究中的所有患者均实现了供者型血液学恢复。与研究A相比，研究B患者的总生存率（OS）和无事件生存率（EFS）显著提高（OS：分别为96.7%和67.9%，P = 0.004；EFS：分别为93.3%和64.3%，P = 0.008）。这些数据表明，含FLU、Cy和ATG的低毒性预处理方案可能是接受非亲缘供者HSCT的SAA患者的最佳方案。
