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Clinical Impact of Panel Based Error Corrected Next Generation Sequencing versus Flow Cytometry to Detect Measurable Residual Disease (MRD) in Acute Myeloid Leukemia (AML)

In MedRxiv
By: Patkar N [Corresponding Author].
Contributor(s): Kakirde C | Shaikh AF | Salve R | Bhanshe P | Chatterjee G | Rajpal S | Joshi S | Chaudhary S | Kodgule R | Ghoghale S | Deshpande N | Shetty D | Khizer SH | Jain H | Bagal B | Menon H | Khattry N | Sengar M | Tembhare P | Subramanian P | Gujral S.
Material type: materialTypeLabelArticlePublisher: 2020Description: .Subject(s): Bone marrow transplantation | Unique molecular identifiers | Measurable Residual Disease | Acute Myeloid Leukemia In: MedRxivSummary: Abstract: We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission and evaluated MRD using sensitive error corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients harbored PI NGS-MRD and 40.9% harbored PC NGS-MRD (median VAF 0.76%). Patients harboring NGS-MRD had a significantly higher cumulative incidence of relapse (p=0.003), inferior overall survival (p=0.001) and relapse free survival (p<0.001) as compared to NGS-MRD negative patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. Patients who cleared PI NGS-MRD had a significantly improved survival as compared to patients who became negative subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were truly missed by NGS as compared to FCM-MRD. NGS-MRD emerged as the most important independent prognostic factor predictive of inferior outcome (p<0.001). We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and advantageous when compared to FCM-MRD in AML treated with conventional therapies.
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Articles Articles Tata Memorial Hospital
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Address for Corresponding Author: nvpatkar@gmail.com

Abstract:
We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission and evaluated MRD using sensitive error corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients harbored PI NGS-MRD and 40.9% harbored PC NGS-MRD (median VAF 0.76%). Patients harboring NGS-MRD had a significantly higher cumulative incidence of relapse (p=0.003), inferior overall survival (p=0.001) and relapse free survival (p<0.001) as compared to NGS-MRD negative patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. Patients who cleared PI NGS-MRD had a
significantly improved survival as compared to patients who became negative subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS.
Only a fraction of cases were truly missed by NGS as compared to FCM-MRD. NGS-MRD emerged as the most important independent prognostic factor predictive of inferior outcome (p<0.001). We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and advantageous when compared to FCM-MRD in AML treated with conventional therapies.

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