Li Si-Qi, Fan Qiao-Zhen, Xu Lan-Ping, Wang Yu, Zhang Xiao-Hui, Chen Huan, Chen Yu-Hong, Wang Feng-Rong, Han Wei, Sun Yu-Qian, Yan Chen-Hua, Tang Fei-Fei, Liu Yan-Rong, Mo Xiao-Dong, Wang Xin-Yu, Liu Kai-Yan, Huang Xiao-Jun, Chang Ying-Jun
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Beijing, China.
Front Oncol. 2020 Mar 17;10:320. doi: 10.3389/fonc.2020.00320. eCollection 2020.
This study compared the effects of pre-transplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT). A retrospective study ( = 202) was performed. MRD was detected by RT-PCR and multiparameter flow cytometry. In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, = 0.009); however, the cumulative incidence of non-relapse mortality (NRM) (7.4% vs. 15.9%, = 0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, = 0.480), and overall survival (OS) (68.8% vs. 76.5%, = 0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, < 0.001) and decreased 4-year LFS (35.9% vs. 71.0%, = 0.024) and OS (35.9% vs. 77.6%, = 0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, = 0.297), NRM (7.3% vs. 16.3%, = 0.187) and the 4-year probability of OS (77.7% vs. 72.3%, = 0.804) and LFS (80.5% vs. 75.7%, = 0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, = 0.021) and a higher 4-year LFS (77.7% vs. 35.9%, = 0.036) and OS (80.5% vs. 35.9%, = 0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; = 0.031), superior LFS (HR, 0.283; = 0.019) and OS (HR, 0.252; = 0.013) in cases with a positive pre-MRD subgroup. Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-vs.-leukemia (GVL) effects.
本研究比较了移植前可测量残留病（pre-MRD）对接受人类白细胞抗原匹配同胞供体移植（MSDT）或接受未处理单倍体相合造血干细胞移植（haplo-SCT）的费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）患者预后的影响。进行了一项回顾性研究（n = 202）。通过逆转录聚合酶链反应（RT-PCR）和多参数流式细胞术检测MRD。在总患者组中，pre-MRD阳性患者的4年累积复发率（CIR）高于pre-MRD阴性患者（26.1%对12.1%，P = 0.009）；然而，非复发死亡率（NRM）的累积发生率（7.4%对15.9%，P = 0.148）、无白血病生存率（LFS）概率（66.3%对71.4%，P = 0.480）和总生存率（OS）（68.8%对76.5%，P = 0.322）相当。在MSDT组中，与pre-MRD阴性患者相比，pre-MRD阳性患者的4年CIR增加（56.4%对13.8%，P < 0.001），4年LFS降低（35.9%对71.0%，P = 0.024），OS降低（35.9%对77.6%，P = 0.011）。在haplo-SCT情况下，pre-MRD阳性和阴性组之间的4年CIR（14.8%对10.7%，P = 0.297）、NRM（7.3%对16.3%，P = 0.187）以及4年OS概率（77.7%对72.3%，P = 0.804）和LFS概率（80.5%对75.7%，P = 0.660）相当。在pre-MRD阳性的亚组患者中，haplo-SCT的4年CIR较低（14.8%对56.4%，P = 0.021），4年LFS较高（77.7%对35.9%，P = 0.036），OS较高（80.5%对35.9%，P = 0.027），高于MSDT。多变量分析显示，在pre-MRD阳性亚组病例中，haplo-SCT与较低的CIR（风险比[HR]，0.288；P = 0.031）、更好的LFS（HR，0.283；P = 0.019）和OS（HR，0.
