Department of Stem Cell Transplantation, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center Research Institute, Tampa, Florida.
Biol Blood Marrow Transplant. 2018 Apr;24(4):726-733. doi: 10.1016/j.bbmt.2017.11.025. Epub 2017 Dec 25.
Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.
全身照射(TBI)已被纳入急性淋巴细胞白血病(ALL)在进行造血细胞移植(HCT)之前的标准预处理方案中。非 TBI 方案采用白消安(Bu)来降低毒性。本回顾性研究分析了 2005 年至 2014 年期间向国际血液和骨髓移植研究中心报告的 18-60 岁、处于首次或第二次完全缓解(CR)、接受 HLA 相容的同胞、亲缘或无关供体 HCT 的 ALL 患者中 TBI 和 Bu 对其结局的影响。819 例患者采用 TBI 加依托泊苷(25%)或环磷酰胺(75%),299 例患者采用静脉注射 Bu 加氟达拉滨(41%)、克拉屈滨(30%)、环磷酰胺(15%)或美法仑(13%)。由于 Bu 方案之间患者结局无显著差异,故将其联合分析。Bu 组患者年龄较大,一般状况较好;达到首次 CR 和接受 HCT 的时间较长;治疗时间较近;更可能接受外周血移植物、抗胸腺细胞球蛋白或酪氨酸激酶抑制剂。Bu 组和 TBI 组的中位随访时间分别为 3.6 年和 5.3 年,调整后的 3 年结局显示,与 TBI 相比,Bu 组治疗相关死亡率为 19% vs. 25%(P=0.04);Bu 组复发率为 37% vs. TBI 组 28%(P=0.007);Bu 组无病生存率(DFS)为 45% vs. TBI 组 48%(P=0.35);Bu 组总生存率(OS)为 57% vs. TBI 组 53%(P=0.35)。多变量分析显示,与 TBI 组相比,Bu 组患者的复发风险更高(相对风险,1.46;95%置信区间,1.15 至 1.85;P=0.002)。尽管 Bu 组复发率较高,但 ALL 患者接受 Bu 预处理方案进行 HCT 后,其 OS 和 DFS 相似。