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. 2020 Jan;98(1):57-67.
doi: 10.1002/cyto.b.21831. Epub 2019 Jun 14.

A High-Sensitivity 10-Color Flow Cytometric Minimal Residual Disease Assay in B-Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2-in-106 and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients

Prashant R Tembhare  1 , Papagudi G Subramanian Pg  1 , Sitaram Ghogale  1 , Gaurav Chatterjee  1 , Nikhil V Patkar  1 , Avinash Gupta  1 , Rahul Shukla  1 , Yajamanam Badrinath  1 , Nilesh Deshpande  1 , Gaurav Narula  2 , Pearl Rodrigues  1 , Karishma Girase  1 , Dilshad Dhaliwal  1 , Maya Prasad  2 , Dhanalaxmi Shetty  3 , Shripad Banavali  2 , Sumeet Gujral  4
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A High-Sensitivity 10-Color Flow Cytometric Minimal Residual Disease Assay in B-Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2-in-106 and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients

Prashant R Tembhare et al. Cytometry B Clin Cytom. 2020 Jan.
Free article

Abstract

Background: Flow-cytometric minimal residual disease (FC-MRD) monitoring is a well-established risk-stratification factor in B-lymphoblastic leukemia/lymphoma (-B-ALL) and is being considered as a basis for deintensification or escalation in treatment protocols. However, currently practiced standard FC-MRD has limited sensitivity (up to 0.01%) and higher false MRD-negative rate. Hence, a highly sensitive, widely applicable, and easily reproducible FC-MRD assay is needed, which can provide a reliable basis for therapeutic modifications.

Methods: A 10-color high-event analysis FC-MRD assay was studied for the evaluation of MRD status at postinduction, (PI; day-35), postconsolidation, (PC; day-78), and subsequent follow-up time-points (SFU) in bone marrow samples from pediatric B-ALL.

Results: One-thousand MRD samples (PI-62.2%; PC-26.5%; and SFU-11.3%) from 622 childhood B-ALL patients were studied. High-event analysis was performed with median 4,452,000 events (range, 839,000 to 8,866,000 events) and >4 million events in 71% samples. MRD was measurable in 43.2% of PI-samples, in 29.4% PC-samples, and in 32.7% SFU-samples. To simulate comparison with standard FC-MRD, we reanalyzed MRD results gating only first 500,000 and first 1000,000 events in 122 PI-MRD positive samples with MRD levels <0.02%. Of these samples gated for 500,000 events and 1000,000 events, 32% and 21.3% were found to be falsely MRD-negative, respectively.

Conclusions: We report an easily reproducible high-sensitivity 10-color FC-MRD assay with the sensitivity of 2-in-106 (0.0002%). It allowed the detection of low-level MRD in samples, which could have been reported negative using the standard FC-MRD with limited event analysis. Thus, this high-sensitivity MRD-methodology can provide a reliable basis for therapeutic modifications in B-ALL. © 2019 International Clinical Cytometry Society.

Keywords: B-cell acute lymphoblastic leukemia; flow cytometry; high sensitivity; minimal residual disease.

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References

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