Background: The proportion of residual leukemic blasts after chemotherapy assessed by multiparameter flow cytometry, is an important prognostic factor for the risk of relapse and overall survival in acute myeloid leukemia (AML). This measurable residual disease (MRD) is used in clinical trials to stratify patients for more or less intensive consolidation therapy. However, an objective and reproducible analysis method to assess MRD status from flow cytometry data is lacking, yet is highly anticipated for broader implementation of MRD testing.
Methods: We propose a computational pipeline based on Gaussian mixture modeling that allows a fully automated assessment of MRD status while remaining completely interpretable for clinical diagnostic experts. Our pipeline requires limited training data, which makes it easily transferable to other medical centers and cytometry platforms.
Results: We identify all healthy and leukemic immature myeloid cells in with high concordance (Spearman's Rho = 0.974) and classification performance (median F-score = 0.861) compared to manual analysis. Using control samples (n = 18), we calculate a computational MRD percentage with high concordance to expert gating (Spearman's rho = 0.823) and predict MRD status in a cohort of 35 AML follow-up measurements with high accuracy (97%).
Conclusions: We demonstrate that our pipeline provides a powerful tool for fast (~3 s) and objective automated MRD assessment in AML.
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http://dx.doi.org/10.1038/s43856-024-00700-x | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659572 | PMC |
Leuk Lymphoma
December 2024
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Over the past two decades, new agents for multiple myeloma (MM) have significantly improved patient outcomes, particularly for those with standard-risk disease, who now have a median overall survival of over a decade. However, this benefit is less pronounced in high-risk and ultra-high-risk MM, where median survival ranges from 3 to 5 years. The definition of HRMM continues to evolve and is driven by the genomic features, disease burden, and medical comorbidities.
View Article and Find Full Text PDFCancer Med
December 2024
Research & Development, SeekIn Inc., San Diego, California, USA.
Background And Purpose: Liver cancer has a high recurrence rate of 50%~70% for early-stage patients. Minimal residual disease (MRD) is strongly linked to liver cancer early recurrence. Identifying MRD through reliable prognostic biomarkers, such as circulating tumor DNA (ctDNA), could significantly benefit these patients by enabling timely intervention and improved outcomes.
View Article and Find Full Text PDFCommun Med (Lond)
December 2024
Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Background: The proportion of residual leukemic blasts after chemotherapy assessed by multiparameter flow cytometry, is an important prognostic factor for the risk of relapse and overall survival in acute myeloid leukemia (AML). This measurable residual disease (MRD) is used in clinical trials to stratify patients for more or less intensive consolidation therapy. However, an objective and reproducible analysis method to assess MRD status from flow cytometry data is lacking, yet is highly anticipated for broader implementation of MRD testing.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
November 2024
St James's Hospital, Leeds, UK. Electronic address:
Treatment of CLL has changed remarkably in the last decade and novel agents are the standard therapy in various jurisdictions. However, the biology of CLL still plays an important part in the treatment choice and disease outcomes. In this post chemo-immunotherapy era for CLL, number of biological factors have lost their clinical significance and most patients will benefit from continuous or time-limited therapy.
View Article and Find Full Text PDFAnn Hematol
December 2024
Department of Hematology and Oncology, Children Hospital of Chongqing Medical University, Chongqing, China.
Blinatumomab has shown to improve survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC). However, data on blinatumomab clearing MRD with high sensitivity remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating low levels of MRD, as detected by droplet digital PCR (ddPCR) but undetectable by MFC, in children with B-ALL.
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