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Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

Tiong, Ing S., Dillon, Richard, Ivey, Adam, Kuzich, James A., Thiagarajah, Nisha, Sharplin, Kirsty M., Kok, Chung Hoow, Tedjaseputra, Aditya, Rowland, James P., Grove, Carolyn S., Abro, Emad, Shortt, Jake, Hiwase, Devendra K., Bajel, Ashish, Potter, Nicola E., Smith, Matthew L., Hemmaway, Claire J., Thomas, Abin, Gilkes, Amanda F., Russell, Nigel H. and Wei, Andrew H. 2021. Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia. Blood Advances 5 (23) , pp. 5107-5111. 10.1182/bloodadvances.2021005455

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Abstract

Abstract Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD−; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Additional Information: Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Publisher: American Society of Hematology
ISSN: 2473-9529
Date of First Compliant Deposit: 19 January 2022
Date of Acceptance: 15 July 2021
Last Modified: 19 Jan 2022 10:30
URI: https://orca.cardiff.ac.uk/id/eprint/146658

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