Department of Hematology and Oncology, Otto von Guericke University, Magdeburg, Germany.
Department of Haematology, Saint Antoine Hospital, INSERM UMR 938, Université Pierre et Marie Curie & Acute Leukemia Working Party European Society for Blood and Marrow Transplantation Office, Paris, France.
Biol Blood Marrow Transplant. 2018 Nov;24(11):2224-2232. doi: 10.1016/j.bbmt.2018.07.007. Epub 2018 Aug 7.
Busulfan/fludarabine (BuFlu) is a widely used conditioning regimen for patients with myeloid malignancies. The sequential FLAMSA (fludarabine + Ara-C + amsacrine chemotherapy) protocol followed by either cyclophosphamide and total body irradiation (FLAMSA-TBI) or cyclophosphamide and busulfan (FLAMSA-Bu) has shown remarkable activity in high-risk acute myelogenous leukemia (AML) patients. Here we compare the outcomes of AML patients transplanted in first complete remission (CR1) or second complete remission (CR2) after conditioning with BuFlu or FLAMSA. Eligible patients had their first allogeneic stem cell transplantation for AML in CR1 or CR2 between January 2005 and June 2016. Donors were matched related or unrelated with up to 1 mismatch. Conditioning consisted of either BuFlu or FLAMSA. Propensity score matching was applied and comparisons were performed using weighted Cox regression. BuFlu conditioning was used in 1197 patients, whereas FLAMSA-TBI and FLAMSA-Bu were used in 258 and 141 patients, respectively. Median follow-up of survivors was 24.72 months. In univariate analysis, relapse incidence (RI) was 30.3%, 21.9%, and 23.1% in the BuFlu, FLAMSA-TBI, and FLAMSA-Bu groups, respectively (P < .01), and nonrelapse mortality at 2 years was 16.1%, 16.4%, and 26.7%, respectively (P < .01). Leukemia-free survival (LFS) at 2 years was 53.6%, 61.6%, and 50.1%, respectively (P = .03). Weighted Cox regression revealed that FLAMSA-TBI compared with BuFlu was associated with lower RI (hazard ratio [HR], .64; 95% confidence interval [CI], .42 to .98; P = .04) and a trend for better LFS (HR, .72; 95% CI, .49 to 1.06; P = .09). These results suggest that compared with BuFlu, conditioning with FLAMSA-TBI leads to reduced RI at 2 years in AML patients transplanted in CR1 or CR2.
白消安/氟达拉滨（BuFlu）是一种广泛应用于髓系恶性肿瘤患者的预处理方案。随后进行的 FLAMSA（氟达拉滨+阿糖胞苷+安吖啶化疗）方案，继之以环磷酰胺和全身照射（FLAMSA-TBI）或环磷酰胺和白消安（FLAMSA-Bu），在高危急性髓系白血病（AML）患者中显示出显著的活性。在这里，我们比较了在 BuFlu 或 FLAMSA 预处理后处于完全缓解（CR1）或第二次完全缓解（CR2）的 AML 患者的移植结果。符合条件的患者于 2005 年 1 月至 2016 年 6 月期间在 CR1 或 CR2 接受了首次同种异体干细胞移植治疗 AML。供者为匹配的相关或不相关供者，有 1 个错配。预处理采用 BuFlu 或 FLAMSA。应用倾向评分匹配，并通过加权 Cox 回归进行比较。BuFlu 预处理组有 1197 例患者，FLAMSA-TBI 组和 FLAMSA-Bu 组分别有 258 例和 141 例患者。幸存者的中位随访时间为 24.72 个月。在单变量分析中，BuFlu、FLAMSA-TBI 和 FLAMSA-Bu 组的复发率（RI）分别为 30.3%、21.9%和 23.1%（P<.01），2 年非复发死亡率分别为 16.1%、16.4%和 26.7%（P<.01）。2 年无白血病生存率（LFS）分别为 53.6%、61.6%和 50.1%（P=.03）。加权 Cox 回归显示，与 BuFlu 相比，FLAMSA-TBI 与较低的 RI 相关（风险比 [HR]，.64；95%置信区间 [CI]，.42 至.98；P =.04），LFS 也有改善趋势（HR，.72；95%CI，.49 至 1.06；P =.09）。这些结果表明，与 BuFlu 相比，AML 患者在 CR1 或 CR2 接受 FLAMSA-TBI 预处理后，2 年时 RI 降低。
