Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington.
Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington.
Biol Blood Marrow Transplant. 2018 May;24(5):956-963. doi: 10.1016/j.bbmt.2017.12.785. Epub 2017 Dec 20.
In this prospective, randomized, phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, aged 2 to 70 years (median, 57), with myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (n = 51) or acute myeloid leukemia (AML; n = 49). Patients received i.v. treosulfan, 14 g/m/day on days -6 to -4 and i.v. fludarabine, 30 mg/m/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0). Donors were related (n = 43) or unrelated (n = 57). When a planned interim analysis showed superior progression-free survival in the TBI arm (P = .04), all subsequent patients received TBI. With a follow-up of 12 to 40 months (median, 20), the 1-year overall survival was 80% for the TBI arm and 69% for the non-TBI arm. The 1-year cumulative incidence of relapse was 22% and 34%, respectively (P = .06). Among patients with low-risk disease the 1-year relapse incidence was 15% and 31% (P = .20) and for patients with high-risk disease, 26% and 36% (P = .18), respectively. Among MDS patients the 1-year relapse incidence was 27% versus 33% (P = .49) and among AML patients 16% versus 35% (P = .05), respectively. The largest difference was among patients with unfavorable cytogenetics, with 1-year relapse incidences of 31% and 63% (P = .18), respectively. Nonrelapse mortality in this high-risk patient population was 9% at 6 months and did not differ between arms. Thus, treosulfan/fludarabine/low-dose TBI provided effective conditioning for allogeneic hematopoietic cell transplantation in high-risk patients up to 70 years of age. The addition of TBI had a more profound effect in patients with AML than in those with MDS. High-risk disease features were associated with a lower overall success rate. Further studies are warranted.
在这项前瞻性、随机、Ⅱ期“挑选胜利者”试验中，我们评估了在 100 例年龄在 2 至 70 岁（中位年龄 57 岁）的骨髓增生异常综合征/慢性髓单核细胞白血病（n=51）或急性髓系白血病（AML；n=49）患者中，使用替莫唑胺/氟达拉滨联合或不联合 2 Gy 全身照射（TBI）的预处理方案，以降低移植后复发率的疗效。患者接受静脉注射替莫唑胺，剂量为 14 g/m2，每天一次，连续 4 天，静脉注射氟达拉滨，剂量为 30 mg/m2，每天一次，连续 2 天，单独或联合 2 Gy TBI（第 0 天）。供者为亲缘（n=43）或非亲缘（n=57）。当计划的中期分析显示 TBI 组具有更好的无进展生存率（P=0.04）时，所有后续患者均接受 TBI。中位随访时间为 12 至 40 个月（20 个月），TBI 组 1 年总生存率为 80%，非 TBI 组为 69%。1 年累积复发率分别为 22%和 34%（P=0.06）。低危疾病患者的 1 年复发率分别为 15%和 31%（P=0.20），高危疾病患者的 1 年复发率分别为 26%和 36%（P=0.18）。骨髓增生异常综合征患者的 1 年复发率为 27%，而急性髓系白血病患者的复发率为 16%（P=0.49）。AML 患者的复发率为 16%，而非 AML 患者的复发率为 35%（P=0.05）。差异最大的是细胞遗传学不良的患者，1 年复发率分别为 31%和 63%（P=0.18）。在高危患者人群中，6 个月时的非复发死亡率为 9%，两组之间无差异。因此，替莫唑胺/氟达拉滨/低剂量 TBI 为 70 岁及以下高危患者的异基因造血细胞移植提供了有效的预处理方案。TBI 的加入对 AML 患者的影响比 MDS 患者更显著。高危疾病特征与总体成功率较低相关。需要进一步研究。
