A United Kingdom Population-Based Study of Survival in Patients Aged 19 to 60 with Acute Myeloid Leukaemia in the Era of Molecular Genetics

Introduction

Acute myeloid leukaemia is a heterogenous disease with variable response to chemotherapy. In order to prognosticate at an individual level numerous cytogenetic and molecular markers may have to be taken into account. Most publications in AML relate to clinical trials and outcomes in this context. We aimed to study outcome in a population-based cohort in the era of molecular genetic testing.

Methods

All patients, aged 19 and over, diagnosed with AML between 2007-2011, throughout the north east of England (population 3.1 million) were identified. This was done by searching weekly multidisciplinary team meeting minutes across the three haematology teams in the region and triangulating these data with cytogenetic and molecular genetic data. Only patients aged 19-60 years (inclusive) at diagnosis are reported. All biopsy specimens were subject to central pathology review.

Results

A total of 344 patients were identified and 150 were aged 19-60. Nineteen patients with acute promyelocytic leukaemia (APL) were excluded. Twelve patients were excluded due to missing data; thus 119 non-APL were analysed: 66 women and 53 men. All patients were considered suitable for intensive therapy and 58 (49%) were included in a national AML trial. Ninety eight out of 119 patients (82%) achieved a complete remission (CR); 79 patients entered CR post cycle 1. 21 patients (17%) did not enter a CR (four died before treatment could commence, nine died during induction, six were refractory and palliated and 2 became aplastic and died before remission status could be ascertained). Thirty-nine patients (40%) subsequently relapsed after achieving CR, 19 of these were successfully re-induced and all but one had an allograft in CR2. Eleven patients failed re-induction and were subsequently palliated and one received an allograft for refractory disease. With a median follow up of 1699 days, the median overall survival (OS) for the population was 603 days. Cytogenetics was a strong predictor of survival with median OS (days) being 225, 508 and not reached (NR) for poor (n=29), standard (n=75) and good (n=15) cytogenetic risk groups respectively (p<0.0006). Analysis by FLT3 ITD and NPM1 mutation status amongst normal karyotype patients demonstrated median OS (days) of 131, 437 and NR for the FLT3+/NPM1- (n=8), FLT3+/NPM1+ or FLT3-/NPM1- (n=36), FLT3-/NPM1+ (n=11) respectively (p=0.0067).

Conclusions

The incidence of AML in adults aged over 18 was 22 per million population per annum. In this population-based cohort of adults aged 19-60 for whom the intention was intensive curative therapy the induction death rate was 7.5 % and CR rate was 85% despite 24% having poor risk genetics. Within the standard risk arm FLT3 positivity conferred a poor risk unless associated with a mutated NPM1. In an unselected population-based cohort FLT3 and NPM1 status remains an important prognostic tool.