Department of Bone Marrow Transplantation of Adults, RM Gorbacheva Research Institute, Pavlov University, Lev Tolstoy Str., 6/8, Saint-Petersburg, Russia, 197022.
Sci Rep. 2023 Oct 5;13(1):16790. doi: 10.1038/s41598-023-43950-w.
The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis. In this study, we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with a median age of 30 (range 18-55) years who previously underwent allo-HSCT, were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT. They were used to model relapse risk with several machine-learning approaches. GBM proved superior to the other algorithms and provided a maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment, and chronic GvHD had the highest value in the model. It was shown that after Day + 100, both error rates do not exceed 22%, while before D + 100, the model fails to make accurate predictions. As a result, we determined BCR::ABL1 levels at which the relapse risk remains low. Thus, the current BCR::ABL1 level less than 0.06% in patients with chronic GvHD predicts low risk of relapse. At the same time, patients without chronic GVHD after allo-HSCT should be classified as high risk with any level of BCR::ABL1. GBM model with posttransplant laboratory values of BCR::ABL1 provides a high prediction of relapse after allo-HSCT in the era of TKIs prophylaxis. Validation of this approach is warranted.
Ph 阳性 ALL 移植后复发会增加死亡风险。因此,需要有工具来预测复发风险并制定预防措施。本研究采用机器学习算法分析移植后数据。回顾性纳入 74 例中位年龄为 30 岁(18-55 岁)的 Ph 阳性 ALL 患者,这些患者此前接受过allo-HSCT,93%的患者在 allo-HSCT 后接受预防性/抢先 TKI。在 allo-HSCT 后指定时间间隔内收集了连续评估和变量值的 BCR::ABL1 水平值,并用几种机器学习方法对复发风险进行建模。GBM 优于其他算法,提供了 0.91 的最大 AUC 评分。BCR::ABL1 水平、allo-HSCT 前后、预测时刻和慢性 GvHD 在模型中具有最高价值。结果表明,在第 +100 天之后,错误率均不超过 22%,而在第 +100 天之前,模型无法做出准确预测。因此,我们确定了复发风险保持较低水平的 BCR::ABL1 水平。因此,慢性 GvHD 患者当前的 BCR::ABL1 水平<0.06%预测复发风险低。同时,allo-HSCT 后无慢性 GVHD 的患者无论 BCR::ABL1 水平如何,均应归类为高风险。在 TKI 预防时代,基于移植后 BCR::ABL1 实验室值的 GBM 模型可对 allo-HSCT 后复发进行高度预测。需要对此方法进行验证。