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

Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study

Dillon, R; Hills, RK; Freeman, SD; Potter, N; Jovanovic, J; Ivey, A; Kanda, AS; ... Grimwade, D; + view all (2020) Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study. Blood , 135 (9) pp. 680-688. 10.1182/blood.2019002959. Green open access

[thumbnail of 78775_0_merged_1567026580.pdf]
Preview
Text
78775_0_merged_1567026580.pdf - Accepted Version

Download (820kB) | Preview

Abstract

Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (alloSCT) and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry (FCM) prior to alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays which have far greater sensitivity. We analysed pre-transplant blood and bone marrow samples by reverse-transcription polymerase chain reaction (RT-qPCR) in 107 patients with NPM1 mutant AML enrolled in the UK National Cancer Research Institute (NCRI) AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies / 105 ABL in the PB and <1000 copies in the BM) and high levels of MRD had an estimated 2y overall survival (OS) of 83%, 63% and 13% respectively (p<0.0001). Focussing on patients with low level MRD prior to alloSCT, those with FLT3 ITD had significantly poorer outcome (hazard ratio, HR, 6.14, p=0.01). Combining these variables was highly prognostic, dividing patients into two groups with 2y OS of 17% and 82% (HR 13.2, p<0.0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y OS 56% vs 96%, HR 3.24, p=0.0005) and in MRD positive patients (2y OS 34% vs 100%, HR 3.78, p=0.003) but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).

Type: Article
Title: Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood.2019002959
Publisher version: http://dx.doi.org/10.1182/blood.2019002959
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: npm1 gene, transplantation, impedance threshold device, ms-like tyrosine kinase 3, mutation, allogeneic stem cell transplant, bone marrow specimen, flow cytometry, follow-up, leukemia, myelocytic, acute
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.ucl.ac.uk/id/eprint/10090007
Downloads since deposit
430Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item