A 35-year-old female presented with fatigue and gum bleeding. On examination, gum hypertrophy with bleeding and splenomegaly were noted. A full blood count revealed a haemoglobin concentration of 8 g/dl, white cell count 120 × 109/l and platelets 15 × 109/l. Peripheral blood leukocytes were 90% myelomonocytic blasts. Bone marrow flow cytometry was CD34– CD33+ CD14+ CD56+ and karyotype was normal.
How would this patient's 'risk' be assessed from the above information?
Would molecular studies reveal further prognostic markers?
The survival for younger patients with acute myeloid leukaemia (AML) is improving decade on decade (Figure 16.1). It is now realistic to attempt curative therapy in almost all such patients. Recent progress has been made through improved understanding of disease biology in relation to outcome from carefully designed phase III clinical trials and has now created an increasingly refined process of disease classification1 and risk stratification.2,3
Outcome of young adults with AML treated within Medical Research Council clinical trials from 1970–2004 (unpublished data reproduced by permission of Professor Alan Burnett).
Contemporary risk assessment is calculated from a combination of factors identified as strongly predictive for outcome from logistic regression multivariate analysis of large, randomized clinical trials. The paradigm for such studies are the UK Medical Research Council (MRC) AML trials, the most informative of these being AML 10/12 (younger adults and children) and AML 11/14 (older patients >60 years).
Cytogenetics is consistently the strongest predictor of clinical outcome in AML. Analysis of the MRC AML 10 trial defined three cytogenetic risk groups:
favourable outcome with translocations t(15;17) and t(8;21) and the inversion inv(16);
adverse risk with –7, –5, abnormal chromosome 3 and complex karyotype (≥5 cytogenetic abnormalities);
standard risk with all other patients including normal karyotype.3
In patients aged <60 years, the proportion of individuals in these three risk groups is 23%, 61% and 16%, respectively.3 Overall survival at 5 years is 61%–69%, 23%–60% and 4%–21%, respectively.3 These data have been confirmed by other study groups, although some karyotypes are categorized into different subgroups. Overall survival at 5 years in the Cancer and Leukemia Group B (CALGB) study was 55%, 24% and 5% for their favourable, intermediate and adverse karyotype groups, respectively.
Thus this patient will be classified as standard risk, based on a standard-risk karyotype. The addition of simple clinical parameters, such as response after therapy course 1, will further refine this risk stratification.2 Preliminary data indicate that a scoring system comprising white cell count, age, sex, secondary versus de novo disease, cytogenetics and response after course 1 will produce a more precise stratification, principally moving approximately 15% of patients from standard to poor ...