第二次异基因造血干细胞移植（HSCT）是对于第一次HSCT后复发的急性白血病患者的治疗选择。虽然对于急性白血病患者，第一次HSCT之前的髓毒性（MA）预处理方案在疾病控制方面比减弱强度（RIC）更好，但第二次异基因HSCT的最佳预处理方案仍然存在争议。最重要的预后因素是第二次HSCT时缓解疾病阶段和第一次到第二次HSCT超过12个月。全骨髓照射（TMI）是一种先进的高精度放射治疗方法，与传统的全身放射疗法（TBI）相比，能够在广泛选择的靶区内投放治疗剂量，同时大大降低对重要器官的辐射。在此，我们报告使用TMI作为髓毒性预处理方案治疗第二次异基因移植的回顾性分析结果，旨在减少毒性。我们研究了13名在2018年3月至2021年11月间接受了第一次异基因HSCT后复发的急性白血病患者，采用高剂量每分段TMI联合替扎醪、氟达拉滨和美法仑的方案。供体类型包括半相合（HAPLO，n = 10）、无关（UD，n = 2）和HLA相容兄弟姐妹（SIB，n = 1）。预处理方案包括8名患者在-8 -7天采用TMI 8 Gy或8名患者在-9 -8 -7天采用TMI 12 Gy，加上替扎醪5 mg / Kg (-6天)，氟达拉滨50 mg /mq 在-5 -4 -3天，美法仑140 mg /mq在-2天给药。TMI采用每日分3次的低分段单剂量4 Gy。中位年龄为45岁（范围19-70岁），7名患者缓解，6名患者在第二次异基因HSCT时有活动性疾病。中位中性粒细胞计数> 0.5×10e9 / L和血小板计数> 20×10e9 / L的时间分别为16天（范围13-22天）和20天（范围14-34天）。所有患者在移植后第30天显示完全供体嵌合。I II级急性移植物抗宿主病（aGvHD）的累积发生率为43％，慢性GvHD（cGVHD）的累积发生率为30％。中位随访时间为1121天（范围200-1540天）。移植后+30天和+100天的与移植相关的死亡率（TRM）均为0。总体TRM、复发率和无病生存率（DFS）的累积发生率分别为27％、7％和67％。这项回顾性研究展示了低分段TMI预处理方案在急性白血病患者接受第二次HSCT时的安全性和有效性，并取得了鼓舞人心的成功：有关移植，早期毒性，GvHD和复发的结果。版权所有©2023 Elsevier Inc.

Second allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for patients with acute leukemia relapsing after a first HSCT. While a myeloablative (MA) conditioning regimen before the first HSCT is considered better than reduced intensity (RIC) in terms of disease control in acute leukemia patients, the optimal conditioning regimen for the second allogeneic HSCT remains controversial. The most important prognostic factors are the remission disease phase at the time of the second HSCT and more than 12 months from the first to the second HSCT. Total Marrow Irradiation (TMI) is an advanced high-precision radiation treatment that delivers therapeutic doses over extensively selected targets while substantially reducing radiation to vital organs compared to conventional Total Body Irradiation (TBI). Herein we report the results of a retrospective analysis on second allogeneic transplantation treated with TMI as a myeloablative conditioning regimen, intending to limit toxicity.We investigated the efficacy of a high dose per fraction TMI in combination with thiotepa, fludarabine and melphalan in 13 consecutive patients with acute leukemia relapsed after a first allogeneic HSCT treated between March 2018 and November 2021.Donor type was haploidentical (HAPLO, n=10), unrelated (UD n=2), and HLA-identical sibling (SIB, n=1). The conditioning regimen consisted of TMI 8 Gy in 5 patients on day -8 -7 or TMI 12 Gy in 8 patients on day -9 -8 -7, plus Thiotepa 5 mg/Kg on day -6, Fludarabine 50 mg/mq on day -5 -4 -3, Melphalan 140 mg/mq on day -2. TMI was delivered in a hypofractionated daily single dose of 4 Gy for three consecutive fractions. The median age was 45 years (range, 19-70 years); 7 patients were in remission, and 6 had active disease at the time of the second allogeneic HSCT.The median time to neutrophil counts of > 0.5×10e9/L was 16 days (range 13-22), and platelet counts of > 20×10e9/L were 20 days (range 14-34), respectively. All patients showed a complete donor chimerism on day 30 after the transplant. The cumulative incidence of grade I II acute GvHD (aGvHD) was 43%, and chronic GvHD (cGVHD) was 30%. The median follow-up was 1121 days (range 200-1540). Day +30 and +100 transplant-related mortality (TRM) was 0. Overall cumulative incidence of TRM, relapse rate, and disease free-survival (DFS) were respectively 27%,7%, and 67%.This retrospective study showed the safety and efficacy of a hypofractionated TMI conditioning regimen in patients with acute leukemia receiving second HSCT with encouraging outcomes regarding engraftment, early toxicity, GvHD, and relapse.Copyright © 2023. Published by Elsevier Inc.