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全身照射联合环磷酰胺与白消安联合环磷酰胺作为急性淋巴细胞白血病预处理方案的长期疗效比较:一项对照研究。

Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study.

机构信息

Hematology Department - BMT Unit, G. Papanicolaou Hospital, Exokhi, 57010, Thessaloniki, Greece.

Department of Radiotherapy, Papageorgiou General Hospital, Thessaloniki, Greece.

出版信息

Ann Hematol. 2018 Oct;97(10):1987-1994. doi: 10.1007/s00277-018-3383-9. Epub 2018 Jun 5.

Abstract

The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen. We studied 151 ALL patients transplanted in first complete remission (CR) (60), other CR (33), or relapsed/refractory disease (58) from sibling (87), and HLA-matched (42) or mismatched (17) unrelated and alternative donors (5). High-dose fractionated TBI-based conditioning was administered in 84. No differences were observed in baseline characteristics, except for disease stage at transplant, donor type, and graft source. With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in non-TBI patients, there was no difference in acute (grades II-IV) or chronic GVHD, thrombotic microangiopathy, and bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group. There was no significant difference in the cumulative incidence (CI) of treatment-related or relapse mortality and disease-free or overall survival (OS). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p = 0.024), advanced disease stage (p = 0.007), and female-to-male donor (p = 0.006). Interestingly, TBI patients younger than 40 years had significantly higher OS (55.1%, p = 0.023) and DFS (48.6%, p = 0.020). In conclusion, high-dose TBI is feasible in younger patients providing better survival. The choice between TBI- or Bu-conditioning regimens remains challenging.

摘要

全身照射(TBI)在异基因造血干细胞移植(HCT)治疗成人急性淋巴细胞白血病(ALL)中的作用仍存在争议。因此,我们调查了接受移植的 ALL 患者的长期治疗结果,旨在确定预后因素和预处理的影响。我们纳入了 1990 年至 2016 年期间接受 TBI 或白消安(Bu)为基础的预处理方案移植的连续 ALL 患者。我们研究了 151 例在首次完全缓解(CR)(60 例)、其他 CR(33 例)或复发/难治性疾病(58 例)中接受移植的 ALL 患者,这些患者来源于同胞(87 例)、HLA 匹配(42 例)或不匹配(17 例)无关供者和替代供者(5 例)。84 例患者接受了高剂量分割 TBI 为基础的预处理。除移植时疾病分期、供者类型和移植物来源外,两组患者的基线特征无差异。在 TBI 组中,中位随访时间为 19.0(0.5-170.5)个月,非 TBI 组为 14.5(1.2-319.1)个月,两组间急性(II-IV 级)或慢性移植物抗宿主病、血栓性微血管病、细菌或真菌感染无差异。仅非 TBI 组病毒感染明显增加。治疗相关或复发死亡率、无病生存率或总生存率(OS)的累积发生率(CI)无显著差异。多因素分析显示,OS 的不良预后因素包括年龄(p=0.024)、晚期疾病分期(p=0.007)和女性对男性供者(p=0.006)。有趣的是,年龄小于 40 岁的 TBI 患者的 OS(55.1%,p=0.023)和 DFS(48.6%,p=0.020)显著较高。总之,TBI 可用于治疗年轻患者,可获得更好的生存。TBI 与 Bu 预处理方案的选择仍具有挑战性。

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