Rodriguez R, Parker P, Nademanee A, Smith D, O'Donnell M R, Stein A, Snyder D S, Fung H C, Krishnan A Y, Popplewell L, Cohen S, Somlo G, Angelopoulou M, Al-Kadhimi Z, Falk P M, Spielberger R, Kogut N, Sahebi F, Senitzer D, Slovak M, Schriber J, Forman S J
City of Hope National Medical Center, Duarte, CA 91010, USA.
Bone Marrow Transplant. 2004 Jun;33(11):1123-9. doi: 10.1038/sj.bmt.1704493.
In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.
为降低接受非亲缘供者造血干细胞移植（URD HSCT）的高危患者的毒性，我们测试了环孢素（CSP）和霉酚酸酯（MMF）联合用药，作为移植物抗宿主病（GVHD）的预防措施，并采用了氟达拉滨/美法仑（Flu/Mel）的减低强度预处理方案。共治疗了22例患有晚期髓系（n = 15）和淋巴系（n = 7）恶性肿瘤的成年患者。所有患者接受氟达拉滨25 mg/m²，共5天，美法仑140 mg/m²，同时每天给予CSP 3 mg/kg，MMF 15 mg/kg，每日3次。中位年龄为49岁（范围18 - 66岁）。除1例骨髓纤维化患者外，所有患者均实现了持久植入。1年非复发死亡率为32%，其中27%死于GVHD。2 - 4级和3 - 4级急性GVHD的累积发生率分别为63%和41%。中位随访18个月，无病生存率（DFS）和总生存率（OS）分别为55%和59%。对于急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者（n = 14），DFS和OS为71%。对于接受第二次移植的患者（n = 14），DFS和OS为57%。总之，该方案在接受URD HSCT的高危患者中具有可接受的毒性，但GVHD发生率较高。观察到对晚期髓系恶性肿瘤患者有令人鼓舞的疾病控制效果。
