Department of Radiation Oncology, Hôpitaux Universitaires Henri Mondor, INSERM U955 University of Paris-Est Créteil, Paris, France; Association of Radiotherapy and Oncology of the Mediterranean Area, Paris, France.
EBMT Paris Study Office, Department of Hematology and Cell Therapy, INSERM U938, Hopital Saint Antoine and University UPMC, Paris, France.
Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):515-526. doi: 10.1016/j.ijrobp.2018.06.015. Epub 2018 Jun 19.
Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12 Gy in 6 fractions over a period of 3 days. The Standard-fractionation compAred to one-daily fRaction total body irrAdiation prior to tranSplant In LEUkemia patieNts (SARASIN) study aimed to compare standard fractionation with once-daily fractionation before transplant in leukemia.
We retrospectively compared TBI regimens delivered in 2993 patients from the European Society for Blood and Marrow Transplantation database, who underwent transplantation between 2000 and 2014 for acute lymphoblastic leukemia (ALL, n = 1729) or acute myeloid leukemia (AML, n = 1264). TBI was delivered as either 12 Gy in 6 fractions (group 1, considered the reference group; 1362 ALL and 857 AML patients), 9 to 12 Gy in 2 fractions (group 2, 173 ALL and 256 AML patients), or 12 Gy in 3 to 4 fractions (group 3, 194 ALL and 151 AML patients).
The median follow-up was 60 and 84 months in ALL and AML patients, respectively. At 5 years, the leukemia-free survival rate, overall survival rate, relapse incidence, and nonrelapse mortality rate were 46.6%, 50.4%, 28.8%, and 24.6%, respectively, in ALL patients and 46.6%, 48.9%, 29.7%, and 23.6%, respectively, in AML patients. In multivariate analyses, the outcomes of groups 2 and 3 were not statistically different from those in group 1. The cumulative incidence of secondary malignancies (SMs) was significantly higher in group 2 (7.2%; P < 10 for group 2 vs group 1). However, group 2 was not associated with an increase in SMs when we considered non-T-cell-depleted transplant patients.
We showed that the 12-Gy fractionated TBI dose delivered either in 2 fractions or in 1 fraction per day over a period of 3 to 4 days resulted in nonsignificant differences in disease control and survival. However, 1-day fractionation may be associated with a higher risk of mucositis and hemorrhagic cystitis. The absence of a significant difference in the SM incidence in the non-T-cell-depleted group should be interpreted with caution in the context of a retrospective study design. Our findings are important to consider for radiation therapy department organization. In-depth analyses of other nonlethal toxicities and late effects are required.
全身照射（TBI）是骨髓清除性预处理方案的主要组成部分。标准技术包括在 3 天内分 6 次给予 12Gy。在白血病患者中，与移植前标准分割比较每日一次分割全身照射（SARASIN）研究旨在比较移植前标准分割与每日一次分割。
我们回顾性比较了欧洲血液和骨髓移植学会数据库中 2993 例患者的 TBI 方案，这些患者在 2000 年至 2014 年间因急性淋巴细胞白血病（ALL，n=1729）或急性髓细胞白血病（AML，n=1264）接受了移植。TBI 采用 12Gy 分 6 次（第 1 组，视为参考组；1362 例 ALL 和 857 例 AML 患者）、9-12Gy 分 2 次（第 2 组，173 例 ALL 和 256 例 AML 患者）或 12Gy 分 3-4 次（第 3 组，194 例 ALL 和 151 例 AML 患者）。
ALL 和 AML 患者的中位随访时间分别为 60 个月和 84 个月。5 年时，ALL 患者的无白血病生存率、总生存率、复发率和非复发死亡率分别为 46.6%、50.4%、28.8%和 24.6%，AML 患者分别为 46.6%、48.9%、29.7%和 23.6%。多变量分析显示，第 2 组和第 3 组的结果与第 1 组无统计学差异。第 2 组（2 组 vs 1 组<10）继发性恶性肿瘤（SM）的累积发生率明显较高。然而，当我们考虑非 T 细胞耗竭移植患者时，第 2 组与 SM 发生率增加无关。
我们表明，12Gy 分次 TBI 剂量在 3-4 天内分 2 次或 1 次/天给予，在疾病控制和生存方面无显著差异。然而，1 天分割可能与更高的粘膜炎和出血性膀胱炎风险相关。在回顾性研究设计的背景下，非 T 细胞耗竭组 SM 发生率无显著差异的结果应谨慎解释。我们的研究结果对于放射治疗科的组织具有重要意义。需要对其他非致命性毒性和晚期效应进行深入分析。
