Wang Yuewen, Mo Xiaodong, Cheng Yifei, Chen Yuhong, Lv Meng, Wang Fengrong, Yan Chenhua, Han Wei, Chen Huan, Xu Lanping, Wang Yu, Zhang Xiaohui, Liu Kaiyan, Huang Xiaojun, Chang Yingjun
Peking University People's Hospital and Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.
Peking-Tsinghua Center for Life Sciences, Beijing, China.
Int J Lab Hematol. 2023 Feb;45(1):72-81. doi: 10.1111/ijlh.13974. Epub 2022 Oct 4.
A higher CD34 cell dose in allografts is associated with faster haematopoietic recovery after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Leukaemia stem cells impair normal bone marrow (BM) niches and induce BM failure during leukemogenesis. However, whether measurable residual disease (MRD), known as the persistence of low-level leukaemic cells, could influence the effects of CD34 cell dose on haematopoietic recovery after transplantation in acute lymphoblastic leukaemia (ALL) patients is unknown.
A total of 975 ALL patients were enrolled and classified into pre-HSCT MRD-positive and MRD-negative subgroups. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariate analysis was performed to determine independent influencing factors from the univariate analysis.
An appropriate CD34 cell dose was positively associated with faster haematopoietic recovery in the total ALL population. More importantly, in pre-HSCT MRD-positive ALL patients, a higher CD34 cell dose (≥2.76 × 10 /kg) was related to faster neutrophil (HR 1.330, 95% CI 1.045-1.692, p = 0.021) and platelet engraftment (HR 1.808, 95% CI 1.412-2.316, p < 0.001) in multivariate analysis. CD34 cell dose was a crucial factor associated with either engraftment or transplant outcomes, although we did not demonstrate direct correlations of CD34 cell dose with relapse, TRM, LFS or OS after allo-HSCT.
Our results indicated that no additional CD34 stem and progenitor cell harvests were needed to ensure successful haematopoietic recovery in pre-HSCT MRD-positive patients compared to pre-HSCT MRD-negative patients.
同种异体造血干细胞移植(allo-HSCT)后,移植物中较高的CD34细胞剂量与更快的造血恢复相关。白血病干细胞在白血病发生过程中会损害正常骨髓龛并导致骨髓衰竭。然而,急性淋巴细胞白血病(ALL)患者中,可测量的残留病(MRD),即低水平白血病细胞的持续存在,是否会影响CD34细胞剂量对移植后造血恢复的影响尚不清楚。
共纳入975例ALL患者,并分为HSCT前MRD阳性和MRD阴性亚组。构建Cox比例风险回归模型用于事件发生时间结局。进行多变量分析以从单变量分析中确定独立影响因素。
在所有ALL患者中,适当的CD34细胞剂量与更快的造血恢复呈正相关。更重要的是,在HSCT前MRD阳性的ALL患者中,多变量分析显示较高的CD34细胞剂量(≥2.76×10⁶/kg)与更快的中性粒细胞植入(风险比[HR] 1.330,95%置信区间[CI] 1.045 - 1.692,p = 0.021)和血小板植入(HR 1.808,95% CI 1.412 - 2.316,p < 0.001)相关。CD34细胞剂量是与植入或移植结局相关的关键因素,尽管我们未证明CD34细胞剂量与allo-HSCT后的复发、移植相关死亡率(TRM)、无白血病生存期(LFS)或总生存期(OS)有直接相关性。
我们的结果表明,与HSCT前MRD阴性患者相比,HSCT前MRD阳性患者无需额外采集CD34干细胞和祖细胞来确保造血恢复成功。