Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
Department of Health Statistics, Second Military Medical University, Shanghai, China.
Int J Lab Hematol. 2021 Feb;43(1):84-92. doi: 10.1111/ijlh.13328. Epub 2020 Sep 3.
Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT) in leukemia. Numerous investigations have demonstrated that minimal residual disease (MRD) before or after alloHSCT is prognostic of relapse risk. These MRD data were collected at specific checkpoints and could not dynamically predict the relapse risk after alloHSCT, which needs serial monitoring.
In the present study, we retrospectively analyzed MRD measured with multi-parameter flow cytometry in 207 acute myeloid leukemia (AML) patients (acute promyelocytic leukemia excluded), and 124 acute B lymphoblastic leukemia (ALL) patients. A three-step method based on joint model was used to build a relapse risk prediction model.
The 3-year overall survival and relapse-free survival rates of the entire cohort were 67.1% ± 2.8% and 61.6% ± 2.8%, respectively. The model included disease status before alloHSCT, acute and chronic graft-versus-host disease, and serial MRD data. The time-dependent receiver operating characteristics was used to evaluate the ability of the model. It fitted well with actual incidence of relapse. The serial MRD data collected after alloHSCT had better discrimination capabilities for recurrence prediction with the area under the curve from 0.67 to 0.91 (AML: 0.66-0.89; ALL: 0.70-0.96).
The joint model was able to dynamically predict relapse-free probability after alloHSCT, which would be a useful tool to provide important information to guide decision-making in the clinic and facilitate the individualized therapy.
在异基因造血干细胞移植(alloHSCT)后,白血病的治疗失败仍然是导致复发的主要原因。大量研究表明,alloHSCT 前后的微小残留病(MRD)与复发风险相关。这些 MRD 数据是在特定的检查点收集的,不能动态预测 alloHSCT 后的复发风险,需要进行连续监测。
本研究回顾性分析了 207 例急性髓系白血病(AML,不包括急性早幼粒细胞白血病)和 124 例急性 B 淋巴细胞白血病(ALL)患者用多参数流式细胞术检测的 MRD。采用基于联合模型的三步法建立复发风险预测模型。
整个队列的 3 年总生存率和无复发生存率分别为 67.1%±2.8%和 61.6%±2.8%。该模型包括 alloHSCT 前疾病状态、急性和慢性移植物抗宿主病以及连续的 MRD 数据。时间依赖性接受者操作特征用于评估模型的能力。它与实际复发率拟合良好。alloHSCT 后收集的连续 MRD 数据对复发预测具有更好的区分能力,曲线下面积从 0.67 到 0.91(AML:0.66-0.89;ALL:0.70-0.96)。
联合模型能够动态预测 alloHSCT 后的无复发生存率,这将是一个有用的工具,可以为临床决策提供重要信息,并促进个体化治疗。