同种异体干细胞移植时复发/难治性急性髓系白血病活动性年轻患者基于flamsa的降低强度调节与清髓调节:来自欧洲血液和骨髓移植学会急性白血病工作组的分析

Eduardo Rodríguez-Arbolí , Myriam Labopin , Johanna Tischer , Arne Brecht , Arnold Ganser , Jürgen Finke , Igor Wolfgang Blau , Nicolaus Kröger , Peter Kalhs , Edouard Forcade , Donald Bunjes , Alexandros Spyridonidis , Bipin Savani , Arnon Nagler , Mohamad Mohty
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引用次数: 11

摘要

在活动性复发/难治性(R/R)急性髓性白血病(AML)中使用清髓调节(MAC)一直受到历史上高非复发死亡率(NRM)的阻碍。在这种情况下,FLAMSA(氟达拉滨,Ara-C和amsacrine)化疗(CT)随后进行降低强度调节(RIC)被认为是一种有效且可能更安全的替代方案。由于支持治疗的改善有助于降低MAC后的NRM率,因此对这两种策略进行了比较重新评估。这是由欧洲血液和骨髓移植学会急性白血病工作组进行的一项基于登记的分析。入选标准包括年龄18 - 50岁、原发性难治、首次或第二次复发的活动性AML、2005年至2018年间首次从匹配的兄弟姐妹供体(MSD)或非亲属供体(UD)进行同种异体干细胞移植、MAC或FLAMSA-RIC。共纳入1018例患者。患者年龄中位数为39岁(18 - 50岁)。258例患者接受了布硫丹(Bu)/环磷酰胺(Cy)治疗,314例接受了Cy/全身照射(TBI), 318例接受了FLAMSA-TBI治疗,128例接受了FLAMSA-CT治疗。中位随访时间为50个月。在单因素分析中,2年复发率(RI) (54%;95%置信区间(CI), 50%-57%),无白血病生存率(LFS) (30%;95% CI, 27%-33%),精致移植物抗宿主病无复发生存率(GRFS) (21%;95% CI, 18%-24%)组间无显著差异。FLAMSA-CT组2年NRM较低(7%,Bu/Cy为16%,Cy/TBI为19%,FLAMSA-TBI为18%);P = .04),以及2年总生存率(OS)的提高(50% vs . Bu/Cy 33%, Cy/TBI 34%, FLAMSA-TBI 36%;p = .03)。这些结果在多变量分析中保持不变(NRM的风险比[HR]: 0.40, P = 0.01;OS HR: 0.65, P = 0.01;但/Cy作为参考)。这些数据表明,由于NRM较低,FLAMSA-CT可能是活动性R/R AML患者的首选调节方案。然而,在我们的分析中观察到的高复发率强调了在这种临床环境中需要新的治疗策略。
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FLAMSA-Based Reduced-Intensity Conditioning versus Myeloablative Conditioning in Younger Patients with Relapsed/Refractory Acute Myeloid Leukemia with Active Disease at the Time of Allogeneic Stem Cell Transplantation: An Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

The use of myeloablative conditioning (MAC) in the setting of active relapsed/refractory (R/R) acute myeloid leukemia (AML) has been hindered by high historical rates of nonrelapse mortality (NRM). FLAMSA (fludarabine, Ara-C, and amsacrine) chemotherapy (CT) followed by reduced-intensity conditioning (RIC) has been proposed as an effective and potentially safer alternative in this scenario. As improvements in supportive care have contributed to decreasing NRM rates after MAC, a comparative reassessment of these two strategies was performed. This was a registry-based analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Eligibility criteria included age 18 to 50 years, primary refractory, first or second relapsed active AML, first allogeneic stem cell transplantation from a matched sibling donor (MSD) or an unrelated donor (UD) performed between 2005 and 2018, MAC or FLAMSA-RIC. A total of 1018 patients were included. The median patient age was 39 years (range, 18 to 50). Two hundred and fifty-eight patients received busulfan (Bu)/cyclophosphamide (Cy), 314 received Cy/total body irradiation (TBI), 318 received FLAMSA-TBI, and 128 received FLAMSA-CT. The median duration of follow-up was 50 months. In univariate analysis, the 2-year relapse incidence (RI) (54%; 95% confidence interval (CI), 50%-57%), leukemia-free survival (LFS) (30%; 95% CI, 27%-33%), and refined graft-versus-host disease-free, relapse-free survival (GRFS) (21%; 95% CI, 18%-24%) were not significantly different between cohorts. Lower 2-year NRM was observed in the FLAMSA-CT group (7% versus 16% in Bu/Cy, 19% in Cy/TBI, and 18% in FLAMSA-TBI; P = .04), as well as increased 2-year overall survival (OS) (50% versus 33% in Bu/Cy, 34% in Cy/TBI, and 36% in FLAMSA-TBI; P = .03). These results were maintained in the multivariate analysis (hazard ratio [HR] for NRM: .40, P = .01; HR for OS: .65, P = .01; Bu/Cy as reference). These data suggest that FLAMSA-CT may be a preferred conditioning regimen in patients with active R/R AML due to lower NRM. Yet, the high relapse rates observed in our analyses emphasize the need for novel therapeutic strategies in this clinical setting.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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