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Next-Generation Sequencing and Minimal Residual Disease in Patients With CLL

By: Cordi Craig
Posted: Wednesday, November 20, 2019

After first-line treatment with fludarabine, cyclophosphamide, and rituximab, many patients with chronic lymphocytic leukemia (CLL) who achieve bone marrow undetectable minimal residual disease status, measured at a 10-4 sensitivity threshold, may still relapse. According to Philip A. Thompson, MB, BS, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, most patients with undetectable minimal residual disease by flow cytometry show detectable levels by next-generation sequencing, which has a sensitivity of 10-6. The report, published in Blood, suggests that a more sensitive assay for minimal residual disease may be necessary.

The investigators used next-generation sequencing to analyze minimal residual disease in 62 patients with CLL who achieved bone marrow undetectable disease status by multicolor flow cytometry after finishing first-line treatment with fludarabine, cyclophosphamide, and rituximab. Patient analyses included bone marrow (n = 57), peripheral blood mononuclear cell (n = 29), and plasma samples (n = 32).

Of the 62 patients, 27.2% achieved undetectable minimal residual disease by next-generation sequencing. The rate of undetectable minimal residual disease was 25% in bone marrow samples, 55% in peripheral blood mononuclear cell samples, and 75% in plasma samples. Undetectable minimal residual disease was more frequent among patients with mutated-IgHV than those with unmutated-IgHV (P = .02). 

After a median follow-up of 81.6 months, patients who achieved undetectable minimal residual disease at the end of the treatment regimen had superior progression-free survival compared with those who had detectable minimal residual disease, regardless of the sample type (median not reached vs. 67 months; P = .02).

“As technology improves, we will increasingly be able to detect very low-level minimal residual disease,” commented the study authors.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.



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