Prognostic significance of monitoring leukemia-associated immunophenotypes by eight-color flow cytometry in adult B-acute lymphoblastic leukemia

X-Q Weng,S-J Chen,Y-M Zhu,J-M Li,B Chen,X-X Zhang,H Yan,J-H Wang,Y Sheng,Z Zhu,J-Q Mi,Z Chen,Q-S Chen,C-L Jiang,Y Shen,T Huang

doi:10.1038/bcj.2013.31

Abstract

Minimal residual disease (MRD) is of the most important factor for predicting prognosis and guiding treatment of acute lymphoblastic leukemia (ALL). In this study, we investigated the prognostic significance of leukemia-associated immunophenotypes (LAIPs) as assessment of index of MRD in 125 adult B-lineage ALL (B-ALL) patients by eight-color flow cytometry. The LAIPs could be identified in 96% and 81.6% of patients with the sensitivity of 10−4 and 10−5, respectively. MRD-negative status could clearly predict a favorable 2-year relapse-free survival (RFS) and overall survival (OS) at the end of induction of complete remission and one cycle of consolidation treatment. Moreover, we identified a group of cases with MRD of 0.001% to <0.01%, which showed significantly higher 2-year relapse rate than those with undetectable one. In multivariate analysis, MRD status was associated with RFS or OS independently. Furthermore, MRD assessed by LAIPs and RQ-PCR assay for patients with BCR-ABL fusion gene yielded concordant results in 89.7% of cases. In conclusion, MRD evaluated by eight-color flow cytometry could provide an important tool to assess treatment response and prognosis precisely in adult B-ALL.

Highlights

It is well known that acute lymphoblastic leukemia (ALL) is a group of heterogeneous diseases in terms of chromosome translocations or molecular genetic abnormalities, which have an important role in the leukemogenesis and risk stratification.1–3 a great proportion of ALL patients lack these typical genetic abnormalities, and more importantly, minimal residual disease (MRD) has an essential role in predicting relapse and even overall survival (OS)
Linear correlation was shown between the percentage of leukemia-associated immunophenotypes (LAIPs) þ cells and different titers of dilution from five bone marrow (BM) samples of B-lineage ALL (B-ALL) diluted into regenerating BM
120 (96%) and 102 (81.6%) out of 125 patients could reach a sensitivity of 0.01% and 0.001% for MRD measurement, respectively, when compared with normal BM cells by eight-color flow cytometry

Summary

Introduction

It is well known that acute lymphoblastic leukemia (ALL) is a group of heterogeneous diseases in terms of chromosome translocations or molecular genetic abnormalities, which have an important role in the leukemogenesis and risk stratification. a great proportion of ALL patients lack these typical genetic abnormalities, and more importantly, minimal residual disease (MRD) has an essential role in predicting relapse and even overall survival (OS). With the development of multi-color flow cytometry and new markers, MFC method for MRD evaluation based on LAIPs is increasingly used in the management of ALL with high applicability, sensitivity and specificity and has been regarded as an important counterpart of PCR detection.. As compared with the classic one (3–4 color assay), it can dramatically save samples and reagents and can offer the possibility of increasing accuracy in population identification.. As compared with the classic one (3–4 color assay), it can dramatically save samples and reagents and can offer the possibility of increasing accuracy in population identification.23 This method has recently been well standardized by the Euro Flow Consortium, which provides researchers with a practicable guideline. As compared with the classic one (3–4 color assay), it can dramatically save samples and reagents and can offer the possibility of increasing accuracy in population identification. this method has recently been well standardized by the Euro Flow Consortium, which provides researchers with a practicable guideline.

Methods

Results

Conclusion