Magenau John M, Braun Thomas, Reddy Pavan, Parkin Brian, Pawarode Attaphol, Mineishi Shin, Choi Sung, Levine John, Li Yumeng, Yanik Gregory, Kitko Carrie, Churay Tracey, Frame David, Riwes Mary Mansour, Harris Andrew, Bixby Dale, Couriel Daniel R, Goldstein Steven C
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA,
Ann Hematol. 2015 Jun;94(6):1033-41. doi: 10.1007/s00277-015-2349-4. Epub 2015 Mar 19.
The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34-0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.
急性髓系白血病（AML）异基因造血干细胞移植（HCT）的最佳预处理强度仍未明确。传统上，清髓性预处理方案可改善疾病控制，但存在更高的非复发死亡率风险。由于使用药代动力学监测的氟达拉滨联合清髓剂量的静脉注射白消安具有良好的耐受性，我们推断与减低强度预处理相比，该方案在不显著增加毒性的情况下可降低复发率。我们回顾性分析了148例连续接受T细胞充足的HCT的AML缓解期患者，这些患者接受了氟达拉滨和静脉注射白消安预处理，剂量分别定义为减低剂量（6.4mg/kg；FluBu2，n = 63）或清髓剂量（12.8mg/kg；FluBu4，n = 85）。FluBu4和FluBu2接受者的早期和晚期非复发死亡率（NRM）分别相似（+100天：4%对0%；5年：19%对22%；p = 0.54）。50岁以上患者中，FluBu4和FluBu2的NRM无差异（24%对22%，p = 0.75）。FluBu4接受者的复发率较低（5年：30%对49%；p = 0.04），尤其是细胞遗传学风险较差的患者（22%对59%；p = 0.02）和50岁以上的患者（28%对51%；p = 0.02）。5年总生存率有利于FluBu4接受者（53%对34%，p = 0.02），多变量分析证实了这一发现（HR：0.57；95%CI：0.34 - 0.95；p = 0.03）。这些数据表明，与FluBu2相比，清髓性FluBu4可能提供相当的NRM、降低复发率并提高生存率，强调了白消安剂量在AML预处理中的重要性。
