Prognostic Factors in Older AML Patients Receiving Intensive and Non-Intensive Therapy: Analysis of the UK AML11 and AML14 Trials.
Authors: Wheatley Keith , Brookes Cassey L. , Hills Robert K. , Goldstone Anthony H. , Milligan Donald W. , Prentice Archie G. , Moorman Anthony V. , Burnett Alan K. 
Published: April 2020

Abstract
AML is a heterogeneous disease and several prognostic factors are well established in younger patients. Less work has been done on parameters affecting outcome in older patients, aged 60 years or over, especially in the majority who receive non-intensive therapy. We used data from the Medical Research Council AML11 trial (n=842) to develop a prognostic index and validated this using the subsequent Leukaemia Research Fund AML14 trial (n=943). Patients in AML11 received intensive standard induction chemotherapy (daunorubicin/Ara-C based); those in AML14 received either similar intensive therapy (AML14I, n=790) or non-intensive therapy with either hydroxyurea or low-dose Ara-C (AML14NI, n=153). Patients with APL were excluded from AML11 analysis since they were not eligible for AML14. Overall survival (OS) was analysed using multivariate Cox regression modelling to identify factors independently related to outcome, and a prognostic index was created for OS using the regression coefficients. From this patients were assigned to 3 equal sized risk groups (good, standard, poor). In AML11, adverse cytogenetics (−5, del(5q), −7, abn(3q), complex), increasing white blood count (WBC), secondary AML, poor performance status (PS) and increasing age were related to poor OS (all p&lt;0.0001). Validation using AML14I confirmed these findings for cytogenetics, WBC and secondary AML, but not for age or PS. In AML14NI, poor OS was predicted by adverse cytogenetics, poor PS and high WBC, but not by age or type of AML (de novo/secondary). OS by risk group for each trial is shown in the table. In all three trials, the differences between risk groups were highly significant (all p&lt;0.0001), though by three years all patients in AML14NI had died apart from one good risk patient. A greater proportion of AML14I patients fell into the good risk group (68%) than in AML11, suggesting that, when a non-intensive option is available, clinicians tend to opt for this for older and/or less fit patients, perhaps explaining the lack of prognostic significance of age and PS in AML14I. Although the outcome of older AML patients is worse than younger patients, this study shows that it is still possible to identify risk groups, using similar parameters to those found in younger patients. These can be used to determine, through prospective stratification of randomised trials by risk group, which patients should be offered intensive therapy with curative intent with the prospect of reasonable survival, and which should not. Similarly, with non-intensive therapy, patients vary considerably in their outcome, though none have good survival, and some patients should probably be offered palliative care only.
Overall survival by risk group Survival at 1 year (%) Survival at 3 years (%) Risk Group Good Standard Poor Good Standard Poor AML11 55 40 15 25 13 7 AML14I 55 30 20 25 8 8 AML14NI 23 12 2 2 0 0