Liu Qi-Fa, Fan Zhi-Ping, Zhang Yu, Jiang Zu-Jun, Wang Chun-Yan, Xu Dan, Sun Jing, Xiao Yang, Tan Huo
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Biol Blood Marrow Transplant. 2009 Nov;15(11):1376-85. doi: 10.1016/j.bbmt.2009.06.017. Epub 2009 Aug 19.
For patients with advanced leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), a major obstacle to success, especially in those with a high leukemia cell burden, is relapse of the underlying disease. To improve the outcome of allo-HSCT for refractory leukemia, we investigated the strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosuppressants therapy for graft-versus-host disease (GVHD) during the early stage after transplantation. A total of 51 patients with refractory leukemia (median age, 30.0 years; unfavorable karyotypes, 49%) received fludarabine (Flu) 30 mg/m(2)/day and cytarabine 2 g/m(2)/day (on days -10 to -6), 4.5 Gy total body irradiation (TBI)/day (on days -5 and -4), and cyclophosphamide (Cy) 60 mg/kg/day and etoposide 600 mg/day (on days -3 and -2) for conditioning. Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion to avoid overwhelming GVHD reactions if acute GVHD (aGVHD) did not develop at day +30. All 51 patients developed regimen-related toxicities (13 with grade III-IV); 93.9% of them achieved complete remission by day +30. Median follow-up was 41 months (range, 6.6 to 92.2 months); 5-year overall survival (OS) and disease-free survival (DFS) were 44.6% +/- 8.1% and 38.2% +/- 7.7%, respectively. Thirteen patients relapsed; the 3-year cumulative incidence of leukemia relapse was 33.3%. On multivariate analysis, cytogenetic status was the only significant pretransplantation factor. Survival was better in patients with grade I or II aGVHD than in those without aGVHD. Our data indicate that the sequential strategy of cytoreductive chemotherapy followed immediately by intensified myeloablative (MA) conditioning for allo-HSCT and rapid tapering of prophylactic immunosuppressants for GVHD in the early stage after transplantation has an acceptable toxicity profile and may be a better approach to treating refractory leukemia.
对于接受异基因造血干细胞移植（allo-HSCT）的晚期白血病患者，尤其是那些白血病细胞负荷高的患者，成功的主要障碍是基础疾病的复发。为了改善难治性白血病的allo-HSCT疗效，我们研究了移植后早期序贯强化预处理以及预防性免疫抑制剂治疗移植物抗宿主病（GVHD）早期快速减量的策略。共有51例难治性白血病患者（中位年龄30.0岁；不良核型占49%）接受氟达拉滨（Flu）30mg/m²/天和阿糖胞苷2g/m²/天（于-10至-6天）、全身照射（TBI）4.5Gy/天（于-5和-4天）以及环磷酰胺（Cy）60mg/kg/天和依托泊苷600mg/天（于-3和-2天）进行预处理。如果在+30天未发生急性移植物抗宿主病（aGVHD），则逐步快速停用环孢素A（CsA）以避免严重的GVHD反应。所有51例患者均出现了与方案相关的毒性反应（13例为III-IV级）；其中93.9%的患者在+30天达到完全缓解。中位随访时间为41个月（范围6.6至92.2个月）；5年总生存率（OS）和无病生存率（DFS）分别为44.6%±8.1%和38.2%±7.7%。13例患者复发；白血病复发的3年累积发生率为33.3%。多因素分析显示，细胞遗传学状态是唯一显著的移植前因素。I或II级aGVHD患者的生存率高于无aGVHD的患者。我们的数据表明，移植后早期采用先进行细胞减灭性化疗紧接着强化清髓性（MA）预处理进行allo-HSCT以及快速减量预防性免疫抑制剂治疗GVHD的序贯策略具有可接受的毒性特征，可能是治疗难治性白血病的更好方法。
