Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Beijing, China.
Peking-Tsinghua Center for Life Sciences, Beijing, China.
Clin Cancer Res. 2019 Mar 15;25(6):1737-1748. doi: 10.1158/1078-0432.CCR-18-1637. Epub 2018 Nov 26.
Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined.
In this prospective trial, among 443 consecutive patients ages 16-60 years with newly diagnosed vo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy ( = 69) or underwent haplo-HSCT ( = 78).
The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; = 0.0004 and 80.8% vs. 53.5%; = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163-0.793; = 0.011], OS (HR 0.361; 95% CI, 0.156-0.832; = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057-0.459; = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation.
Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
尽管在移植前使用抗胸腺细胞球蛋白（ATG）和粒细胞集落刺激因子（G-CSF）刺激移植物后进行清髓性 HLA 单倍体相合造血干细胞移植（haplo-HSCT）已被证实可作为 HLA 匹配同胞供体（MSD）来源 HSCT 的替代方法，但haplo-HSCT 对达到首次完全缓解（CR1）的中危（int-risk AML）急性髓系白血病（AML）患者缓解后治疗的影响尚未明确。
在这项前瞻性试验中，纳入了 443 例年龄在 16-60 岁之间、新诊断为 voAML 且具有中危细胞遗传学特征的连续患者，其中 147 例分子学中危 AML 患者在 2 个疗程诱导后达到 CR1，并在缓解后 4 个月时仍处于 CR1，他们分别接受化疗（n=69）或 haplo-HSCT（n=78）。
haplo-HSCT 组的 3 年无白血病生存（LFS）和总生存（OS）显著高于化疗组（74.3% vs. 47.3%；P=0.0004 和 80.8% vs. 53.5%；P=0.0001）。在多变量分析中，进行了倾向性评分调整后，缓解后治疗（haplo-HSCT 与化疗）是影响 LFS（HR 0.360；95%CI，0.163-0.793；P=0.011）、OS（HR 0.361；95%CI，0.156-0.832；P=0.017）和累积复发率（HR 0.161；95%CI，0.057-0.459；P=0.001）的独立危险因素，无论是在整个队列中还是在第二次巩固治疗后最小残留疾病分层中。
在 CR1 期间，清髓性 haplo-HSCT 联合 ATG+G-CSF 作为缓解后治疗在中危 AML 患者中优于化疗。在没有 HLA-MSD 的情况下，haplo-HSCT 可能成为中危 AML 的一线缓解后治疗方法。在 CR1 中，haplo-HSCT 作为中危 AML 的一线缓解后治疗可能优于化疗。
