Real‐world utility of early measurable residual disease assessments by multi‐parametric flow cytometry in adult patients with B‐lymphoblastic leukemia receiving Hyper‐CVAD induction chemotherapy

微小残留病 医学 肿瘤科 内科学 诱导化疗 化疗 多元分析 流式细胞术 白血病 免疫学
作者
Rithin Nedumannil,David Ritchie,Ashish Bajel,Ashley P. Ng,Simon Harrison,David Westerman
出处
期刊:European Journal of Haematology [Wiley]
卷期号:110 (2): 168-176
标识
DOI:10.1111/ejh.13890
摘要

Abstract Multi‐parametric flow cytometry (MFC) has a well‐established role in measurable residual disease (MRD) monitoring in patients with B‐lymphoblastic leukemia (B‐ALL). However, the optimal time‐point (TP) for early MRD testing and associated prognostic impact remain undefined in adult B‐ALL patients receiving Hyper‐CVAD induction chemotherapy. To evaluate the utility of MRD analysis after one cycle (TP1) in comparison to MRD analysis after two cycles (TP2) of induction treatment with Hyper‐CVAD chemotherapy, we studied 49 adult B‐ALL patients over a 10‐year period (2010–2020) who had available bone marrow samples for morphological and MFC MRD assessments at the two separate TPs. Median times to TP1 and TP2 relative to start of treatment were 21 and 45 days, respectively. When censored at transplant, achievement of MRD negativity at TP1 was not associated with a statistically significant improvement in either event‐free survival (EFS) ( p = .426) or overall survival (OS) ( p = .335) when compared to patients with MRD positivity. In contrast, achieving MRD negativity at TP2 was associated with a statistically significant improvement in both EFS ( p = ·005) and OS ( p = .047) over patients who remained MRD positive. Multivariate analysis demonstrated that KMT2A ‐rearrangement and MRD positivity at TP2 were the only significant predictors of outcome, correlating with worse EFS and OS. Therefore, in the absence of residual morphologic disease, MRD analysis after one cycle of Hyper‐CVAD induction chemotherapy did not provide additional benefit with regard to risk stratification or correlation with survival outcomes when compared to MRD testing after two cycles of Hyper‐CVAD in adult B‐ALL patients.
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