Schwarer Anthony P, Butler Jason, Jackson Kathryn, Beligaswatte Ashanka, Martin Louisa, Kennedy Glen, Daniela Zantomio, Lewis Ian, Hiwase Devendra, Wight Joel, He Simon, Grigg Andrew, Morris Kirk, Mollee Peter, Marlton Paula
Eastern Health Monash University Clinical School, Melbourne, Australia.
Haematology Department, Austin Hospital, Melbourne, Australia.
Hemasphere. 2018 Nov 28;2(6):e158. doi: 10.1097/HS9.0000000000000158. eCollection 2018 Dec.
The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, < 0.01) which did not lead to an improved overall survival (48% vs 43%, = 0.18) or disease-free survival (DFS) (39% vs 45%, = 0.95). We noted that, after censoring for allogeneic hematopoetic stem cell transplant (alloHSCT) in CR1, the cumulative incidence of relapse was lower in the HiDAC consolidation cohort in patients with intermediate risk cytogenetics (68% vs 44%, = 0.01), which lead to a greater DFS (30% vs 47%, = 0.095). In the patients with adverse risk cytogenetics, the RR was numerically greater in the HiDAC consolidation cohort (52% vs 80%, = 0.60) which lead to a lower DFS (27% vs 4%, = 0.11). Our data show that, although the HiDAC induction cohort (1 cycle of HiDAC) achieved a greater CR rate, there were no overall survival differences between the 2 cohorts, and that the HiDAC consolidation cohort (2 cycles of HiDAC) had a lower RR and greater DFS in those patients with intermediate risk cytogenetics who did not undergo alloHSCT in CR1.
通过给予大剂量阿糖胞苷(HiDAC),急性髓系白血病(AML)患者的治愈比例有所提高。目前仍不确定是将HiDAC用于诱导治疗还是巩固治疗,以及是否需要≥1个周期的HiDAC。我们对416例成年AML患者进行了回顾性研究,排除了良好风险的细胞遗传学情况,将基于HiDAC的单周期治疗后再进行2个周期标准剂量阿糖胞苷(SDAC)治疗的患者(HiDAC诱导组)与基于SDAC的化疗后再进行2个周期基于HiDAC的化疗的患者(HiDAC巩固组)进行了比较。HiDAC诱导组的完全缓解(CR)率更高(90%对78%,<0.01),但这并未导致总生存期(48%对43%,=0.18)或无病生存期(DFS)得到改善(39%对45%,=0.95)。我们注意到,在对处于完全缓解期1(CR1)的异基因造血干细胞移植(alloHSCT)进行审查后,HiDAC巩固组中细胞遗传学处于中等风险的患者复发的累积发生率较低(68%对44%,=<0.01),这导致了更高的DFS(30%对47%,=0.095)。在细胞遗传学处于不良风险的患者中,HiDAC巩固组的风险比(RR)在数值上更高(52%对80%,=0.60),这导致了更低的DFS(27%对4%,=0.11)。我们的数据表明,尽管HiDAC诱导组(1个周期的HiDAC)达到了更高的CR率,但两组之间的总生存期并无差异,并且HiDAC巩固组(2个周期的HiDAC)在那些细胞遗传学处于中等风险且在CR1期未接受alloHSCT的患者中复发率更低且DFS更高。