传统的非兄弟（同源异体）造血干细胞移植（alloHCT）疗法对于年龄较大的患者和有合并症的患者来说，带来的效果不佳。我们的假设是，在较长时间内分次给予骨髓毒性剂布司他丹，可以降低非复发性死亡率（NRM），同时保持抗白血病效应。在这里，我们为血液恶性肿瘤患者进行了Ⅱ期试验，接受同血型相关或无关的alloHCT。参与者在移植前的-20天和-13天接受80mg/m2的布司他丹门诊治疗。随后在-6到-2天给予40mg/m2的氟达拉滨，然后以达到20,000mol/min下的目标曲线区域为整个过程的布司他丹剂量。主要终点是100天的非复发性死亡率。共纳入了78名患者，年龄中位数为61岁（范围39-70岁），其中急性白血病（24%），骨髓增生异常综合症（27%）或骨髓增殖性疾病/慢性粒细胞白血病（44%）。 34人（44%）的骨髓移植特异性合并症指数（HCT-CI）大于3。随访时间中位数为36.4个月（范围2.9-51.5个月），100天、1年和3年的非复发性死亡率分别为3.8%（95% CI，0-8.1%），8%（95% CI，2-14%）和9.3%（95% CI，2.6-15.9%），年龄或HCT-CI评分无显著差异。1年和3年的复发率分别为10%（95% CI，4-17%）和18%（95% CI，9-27%）。3年总生存率为80%（95% CI，72-90%），对于>60岁和<60岁的患者，以及HCT-CI>3和HCT-CI<3的患者，总生存率相似。总体而言，我们发现毒性骨髓抹除分次给药剂量的布司他丹疗法具有较低的非复发性死亡风险，不会增加复发率，导致较好的存活水平，即使是年龄较大的患者或合并症患者。版权所有©2023年美国血液学会。

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce non-relapse mortality (NRM), while retaining anti-leukemic effects. Here, we performed a phase II trial for adults with hematological malignancies receiving matched related or unrelated alloHCT. Participants received busulfan 80mg/m2 outpatient on days -20 and -13 before transplant. Fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve a target area under the curve of 20,000mol/min for the whole course. The primary endpoint was day 100 NRM. Seventy-eight patients were included, with a median age of 61 (range 39-70) years, transplanted for acute leukemia (24%), MDS (27%), or MPD/CML (44%). HCT specific comorbidity index (HCT-CI) was >3 in 34 (44%). With a median follow-up of 36.4 (range 2.9-51.5) months, 100-day, 1-year and 3-year NRM was 3.8% (95%CI, 0-8.1%), 8% (95%CI, 2-14%), and 9.3% (95%CI, 2.6-15.9%), without a significant difference by age or HCT-CI score. One-year and 3-year relapse incidence was 10% (95%CI, 4-17%) and 18% (95%CI, 9-27%), respectively. Three-year overall survival was 80% (95%CI, 72-90%) and was similar for patients >60 and <60 years of age, as well as those with HCT-CI>3 and HCT-CI<3. Overall, we found that a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities.Copyright © 2023 American Society of Hematology.