UCL Discovery Stage
UCL home » Library Services » Electronic resources » UCL Discovery Stage

Additional impact of mutational genotype on prognostic determination in resistant and relapsed acute myeloid leukaemia

Linch, DC; Hills, RK; Gilkes, A; Burnett, AK; Russell, N; Gale, RE; (2021) Additional impact of mutational genotype on prognostic determination in resistant and relapsed acute myeloid leukaemia. Leukemia Research , 108 , Article 106553. 10.1016/j.leukres.2021.106553. Green open access

[thumbnail of Linch et al_Leuk Res_final .pdf]
Preview
Text
Linch et al_Leuk Res_final .pdf - Accepted Version

Download (1MB) | Preview

Abstract

Outcome after failure of initial therapy in younger adult patients with acute myeloid leukaemia (AML) is highly variable. Cytogenetics, length of first remission (CR1) before relapse, and allogeneic transplantation are known prognostic factors, but the contribution of leukaemic genotype is less clear, particularly in resistant disease. Of 5,651 younger adult patients entered into UK MRC/NCRI AML trials between 1988 and 2014 with available FLT3ITD and NPM1 genotype, 326 (6%) had resistant disease and 2338 (41 %) relapsed after achieving CR1. Overall survival (OS) was significantly higher in relapsed compared to resistant disease (p = 0·03). Independent favourable prognostic factors for OS in resistant disease included lower blast cell percentage after two courses of induction therapy (p = 0.0006) and NPM1 mutant (NPM1MUT) (p = 0.04). In relapsed disease, longer CR1 was a favourable independent factor for attainment of CR2 (p < 0.0001) and OS from time of relapse (p < 0.0001), but CR2 rate and OS from relapse were significantly worse in those who had received an allograft in CR1 (respectively p < 0.05, p < 0·002). NPM1MUT was marginally beneficial for OS (p = 0.04). FLT3ITD and DNMT3AMUT were adverse factors for OS (respectively p < 0.0001, p = 0.02). Mutational analysis adds additional independent prognostic information to demographic features and previous therapy in patients with resistant and relapsed disease.

Type: Article
Title: Additional impact of mutational genotype on prognostic determination in resistant and relapsed acute myeloid leukaemia
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.leukres.2021.106553
Publisher version: https://doi.org/10.1016/j.leukres.2021.106553
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Acute myeloid leukaemia; Leukaemic cell genotype; Prognostic factors; Resistant disease; Relapse post first remission; NPM1 mutation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10137846
Downloads since deposit
3,996Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item