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.
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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 |
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