Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), University of Seville, Seville, Spain.
Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Sorbonne University, and INSERM UMRs 938, Paris, France.
Bone Marrow Transplant. 2022 Jun;57(6):934-941. doi: 10.1038/s41409-022-01611-y. Epub 2022 Apr 7.
Comparative data of fludarabine, cytarabine and amsacrine (FLAMSA) chemotherapy followed by busulfan (Bu)-based reduced-intensity conditioning (RIC) (FLAMSA-Bu) versus RIC regimens are lacking in patients with active relapsed/refractory (R/R) acute myeloid leukemia (AML) at the time of allogeneic hematopoietic stem cell transplantation (alloSCT). Here, we retrospectively analyzed outcomes after FLAMSA-Bu versus fludarabine/busulfan (FluBu2) conditioning in this patient population. A total of 476 patients fulfilled the inclusion criteria, of whom 257 received FluBu2 and 219 FLAMSA-Bu. Median follow-up was 41 months. Two-year non-relapse mortality (21%), graft-versus-host disease-free, relapse-free survival (24%) and chronic graft-versus-host disease (GVHD) (29%) were not statistically different between cohorts. FLAMSA-Bu was associated with lower 2-year relapse incidence (RI) (38 vs 49% after FluBu2, p = 0.004), and increased leukemia-free survival (LFS) (42 vs 29%, p = 0.001), overall survival (47 vs 39%, p = 0.008) and grades II-IV acute GVHD (36 vs 20%, p = 0.001). In the multivariate analysis, FLAMSA-Bu remained associated with lower RI (HR 0.69, p = 0.042), increased LFS (HR 0.74, p = 0.048) and a higher risk of acute GVHD (HR 2.06, p = 0.005). Notwithstanding the limitations inherent in this analysis, our data indicate that FLAMSA-Bu constitutes a tolerable conditioning strategy, resulting in a long-term benefit in a subset of patients reaching alloSCT with active disease.
在接受异基因造血干细胞移植（alloSCT）时患有活跃的复发/难治性（R/R）急性髓系白血病（AML）的患者中，缺乏氟达拉滨、阿糖胞苷和安吖啶（FLAMSA）化疗后紧接着用白消安（Bu）为基础的减低强度调理（RIC）（FLAMSA-Bu）与 RIC 方案的比较数据。在这里，我们回顾性分析了在这一患者人群中，FLAMSA-Bu 与氟达拉滨/白消安（FluBu2）调理后的结局。共有 476 名患者符合纳入标准，其中 257 名接受 FluBu2，219 名接受 FLAMSA-Bu。中位随访时间为 41 个月。两组患者的 2 年非复发死亡率（21%）、无移植物抗宿主病-无复发存活率（24%）和慢性移植物抗宿主病（GVHD）（29%）无统计学差异。FLAMSA-Bu 与较低的 2 年复发率（RI）（FluBu2 后 38%比 49%，p=0.004）相关，与较高的无白血病存活率（LFS）（42%比 29%，p=0.001）、总存活率（47%比 39%，p=0.008）和 2-4 级急性 GVHD（36%比 20%，p=0.001）相关。在多变量分析中，FLAMSA-Bu 仍与较低的 RI（HR 0.69，p=0.042）、较高的 LFS（HR 0.74，p=0.048）和较高的急性 GVHD 风险（HR 2.06，p=0.005）相关。尽管该分析存在固有局限性，但我们的数据表明，FLAMSA-Bu 构成一种可耐受的调理策略，在接受 alloSCT 治疗的一部分疾病活跃的患者中带来了长期获益。
