Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
Biol Blood Marrow Transplant. 2011 Jul;17(7):1025-32. doi: 10.1016/j.bbmt.2010.10.030. Epub 2010 Nov 1.
Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients (median age, 57 years; range, 23-70 years) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total-body irradiation (200 cGy) with or without antithymocyte globulin followed by related donor allogeneic HCT at the University of Minnesota between 2002 and 2008. The cohort included 45 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 with aggressive non-Hodgkin lymphoma (NHL), 8 with indolent NHL, 10 with Hodgkin lymphoma (HL), 10 with myeloma, and 23 with acute lymphocytic leukemia, chronic myelogenous leukemia, other leukemias, or myeloproliferative disorders. The probability of 4-year overall survival was 73% for patients with indolent NHL, 58% for those with aggressive NHL, 67% for those with HL, 30% for those with AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse in these patients were 0%, 32%, 50%, 33%, and 38%, and those for progression-free survival were 73%, 45%, 27%, 27%, and 10%. The incidence of treatment-related mortality was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease was 38% at day +100, and that of chronic graft-versus-host disease was 50% at 2 years. Multivariate analysis revealed superior overall survival and progression-free survival in patients with both indolent and aggressive NHL compared with those with AML/MDS, HL, or myeloma. Worse 1-year treatment-related mortality was observed in patients with a Hematopoietic Cell Transplantation Comorbidity Index score ≥ 3 and in cytomegalovirus-seropositive recipients. These results suggest that (1) RIC conditioning was well tolerated by an older, heavily pretreated population; (2) patients with indolent and aggressive NHL respond well to RIC conditioning, highlighting the importance of the graft-versus-lymphoma effect; and (3) additional peri-transplantation manipulations are needed to improve outcomes for patients with AML/MDS or myeloma receiving RIC conditioning before HCT.
对于不能承受清髓性预处理的血液系统恶性肿瘤患者，降低强度预处理（RIC）可扩大同种异体造血细胞移植（HCT）的治疗效果。我们前瞻性分析了 2002 年至 2008 年期间在明尼苏达大学接受环磷酰胺、氟达拉滨和全身照射（200cGy）联合或不联合抗胸腺细胞球蛋白的同种异体 HCT 的 123 例血液系统恶性肿瘤患者（中位年龄 57 岁；范围，23-70 岁）的结局。该队列包括 45 例急性髓性白血病（AML）或骨髓增生异常综合征（MDS）患者、27 例侵袭性非霍奇金淋巴瘤（NHL）患者、8 例惰性 NHL 患者、10 例霍奇金淋巴瘤（HL）患者、10 例多发性骨髓瘤患者和 23 例急性淋巴细胞白血病、慢性髓性白血病、其他白血病或骨髓增生性疾病患者。惰性 NHL 患者的 4 年总生存率为 73%，侵袭性 NHL 患者为 58%，HL 患者为 67%，AML/MDS 患者为 30%，多发性骨髓瘤患者为 10%。这些患者的复发相关结果分别为 0%、32%、50%、33%和 38%，无进展生存相关结果分别为 73%、45%、27%、27%和 10%。第 100 天和 1 年的治疗相关死亡率分别为 14%和 22%。第 100 天急性移植物抗宿主病（GVHD）Ⅱ-Ⅳ级发生率为 38%，2 年慢性 GVHD 发生率为 50%。多变量分析显示，与 AML/MDS、HL 或多发性骨髓瘤患者相比，惰性 NHL 和侵袭性 NHL 患者的总生存率和无进展生存率均有改善。造血细胞移植合并症指数（HCT-CI）评分≥3 分和巨细胞病毒血清阳性的患者，1 年治疗相关死亡率较高。这些结果表明：（1）RIC 预处理方案可被老年、预处理较多的患者良好耐受；（2）惰性 NHL 和侵袭性 NHL 患者对 RIC 预处理反应良好，突出了移植物抗淋巴瘤效应的重要性；（3）AML/MDS 或多发性骨髓瘤患者接受 RIC 预处理后行同种异体 HCT 前，需要进行额外的移植前处理以改善患者结局。
