Parker Jane E, Shafi Tariq, Pagliuca Antonio, Mijovic Aleksandar, Devereux Stephen, Potter Mike, Prentice H Grant, Garg Mamta, Yin John A, Byrne Jenny, Russell Nigel H, Mufti Ghulam J
Department of Haematological Medicine, Guy's, King's, Thomas' School of Medicine, London, UK.
Br J Haematol. 2002 Oct;119(1):144-54. doi: 10.1046/j.1365-2141.2002.03796.x.
Conventional allogeneic stem cell transplantation (SCT) for myelodysplastic syndrome (MDS) is associated with excessive procedure-related mortality. The outcome following volunteer-unrelated donor (VUD) or sibling allogeneic SCT was therefore evaluated in 23 MDS patients conditioned with reduced-intensity regimens (fludarabine/busulphan/Campath-1H) because of advanced age (48 vs 37 years, P = 0.002) and/or co-morbidity (19 vs 3, P < 0.0001) which precluded conventional transplantation, and compared with 29 treated with standard protocols [busulphan/cyclophosphamide (Bu/Cy); Bu/Cy/total-body irradiation/Campath-1G]. Graft-versus-host disease (GVHD) prophylaxis comprised of cyclosporine/methotrexate. One hundred per cent donor engraftment (variable number tandem repeat analysis/cytogenetics/fluorescence in situ hybridization) was achieved in 18/19 (95%) evaluable patients receiving reduced-intensity regimens, although six (32%) have subsequently shown mixed chimaerism. Reduced-intensity conditioning was associated with significantly reduced duration of aplasia, less mucositis, fever, antibiotic, analgesia, parenteral nutrition use, less acute and chronic GVHD, and lower early procedure-related mortality [two (9%) vs nine (31%), P < 0.05]. Six patients relapsed (two standard, four reduced-intensity) and two (reduced-intensity) experienced late graft failure. The 2 year actuarial overall/disease-free survival (OS/DFS) was 48/39% in the reduced-intensity arm and 44/44% in the standard group. The 2 year non-relapse mortality was 31% and 50% respectively. In VUD recipients, OS was superior in the reduced-intensity arm (49%vs 34%). Predictors of DFS included good/intermediate-risk karyotype, low/intermediate-1 International Prognostic Scoring system score, human leucocyte antigen compatibility and attainment of complete remission. Our data demonstrates that VUD or sibling allogeneic SCT following reduced-intensity conditioning is feasible in high-risk MDS patients considered unsuitable for standard transplantation and is associated with comparable 3.5 year DFS to those receiving conventional regimens.
传统的异基因干细胞移植（SCT）治疗骨髓增生异常综合征（MDS）与过高的与治疗相关的死亡率相关。因此，对23例因年龄较大（48岁对37岁，P = 0.002）和/或合并症（19例对3例，P < 0.0001）而无法进行传统移植的MDS患者进行了评估，这些患者接受了降低强度方案（氟达拉滨/白消安/Campath-1H）预处理的志愿无关供者（VUD）或同胞异基因SCT，并与29例接受标准方案[白消安/环磷酰胺（Bu/Cy）；Bu/Cy/全身照射/Campath-1G]治疗的患者进行了比较。移植物抗宿主病（GVHD）预防采用环孢素/甲氨蝶呤。在19例接受降低强度方案的可评估患者中，18例（95%）实现了100%供者植入（可变数目串联重复分析/细胞遗传学/荧光原位杂交），尽管其中6例（32%）随后出现了混合嵌合体。降低强度预处理与显著缩短的再生障碍期、较少的粘膜炎、发热、抗生素、镇痛剂、肠外营养使用、较少的急性和慢性GVHD以及较低的早期与治疗相关的死亡率相关[2例（9%）对9例（31%），P < 0.05]。6例患者复发（2例标准方案，4例降低强度方案），2例（降低强度方案）出现晚期移植物失败。降低强度组的2年实际总生存率/无病生存率（OS/DFS）为48%/39%，标准组为44%/44%。2年非复发死亡率分别为31%和50%。在VUD受者中，降低强度组的OS更高（49%对34%）。DFS的预测因素包括良好/中等风险核型、低/中等-1国际预后评分系统评分、人类白细胞抗原相容性以及达到完全缓解。我们的数据表明，在被认为不适合标准移植的高危MDS患者中，降低强度预处理后的VUD或同胞异基因SCT是可行的，并且与接受传统方案的患者具有相当的3.5年DFS。
