TO THE EDITOR Survival in acute leukaemia is age-dependent and unintentional age biases in trials/studies may be a major cause of inconsistency when comparing outcome between studies. Assessing clinical outcome using a population-based data set collected over a prolonged time period linked to cytogenetics has revealed the full extent of the heterogeneity based on age, suggesting a rethink of study design in leukaemia trials is required. Acute myeloid leukaemia (AML), in the adult age group (>15 years), is a heterogeneous disease group with differing chromosomal abnormalities associated with the different biological subtypes of the disease, the incidence of subtypes varying over different age groups. Response to therapy varies between age groups, in part due to the different nature of the disease. Few studies in leukaemia have been conducted on unselected cohorts of patients and trials continue to be performed over wide age bands on highly selected but mixed biological patients populations.1 In particular, there is under-representation of older patients in trials and studies and even where they are included substantial selection takes place.2 Since 1983 the Northern Regional Haematology Group in the UK has had in place a process by which data on total numbers of patients diagnosed with acute leukaemia in a designated population have been assessed alongside treatment outcome on standard therapeutic regimens or on trials both regional and national, and linked to cytogenetic analysis at diagnosis in the majority of patients.3 We have prospectively collected data of de novo acute myeloid leukaemia linked to clinical outcome over 15 years for patients aged 0–55 years (n = 398) and for 10 years in patients >55 years (n = 692) for a geographical-based population of 3.01 million. Figure 1 demonstrates the pattern of survival in age-based cohorts with AML. These data represent the absolute numbers of leukaemias presenting over unit time for a unit population and by extrapolation it would be possible to calculate with accuracy the numbers of patients potentially available for a given study or trial within defined age groups. In a trial constructed to study patients between the ages of 15 and 59, which is the case with most current studies of intensive treatment in acute leukaemia, there is a tendency for physicians to enter younger patients within the specified age range, especially when the chemotherapy protocols are particularly aggressive. As a result the median age of a population varies from study to study due to patient selection. Looking at the survival data in Figure 1 it can be seen that relatively minimal changes in the median age of the population could change the shape of the survival curve irrespective of the form of chemotherapy utilised and makes comparisons with other studies, ostensibly covering the same age range, very difficult and potentially inaccurate. If such studies also include survival data in children, who have an overall better survival due to less toxic death, then once again generalised overall conclusions could be misleading.4 Within our study population it has also been possible to collect cytogenetic data on the initial diagnostic samples in 70% of cases over the period of the study, but more recently this has been attempted on 90% of patients and has allowed us to make a population-based assessment of the prognostic significance of specific translocations. It has been reported in a number of studies that three particular abnormalities, t(15;17) (acute promyelocytic leukaemia), t(8;21), and inv(16) have a substantially improved prognosis.5 Indeed, under the age of 30 years patients within our population with these 'good risk' abnormalities do appear to have a particularly favourable prognosis. However, in the age groups over the age of 30 years, those with these 'good risk' chromosome types are both reduced in number and have a survival which is not dissimilar to their age group overall (Figure 2). In conclusion, our data indicate that when designing leukaemia trials, even in younger patients, in the future it will be necessary to consider the use of much narrower age bands and specific cytogenetic types. In order to recruit sufficient numbers for such homogeneous leukaemia trials it will mean an increased uptake of the population approach to study in leukaemia and that studies will need to be spread over large populations, internationally if necessary. It is critical that such age-limited cytogenetic limited studies are brought forward for consideration if clinical leukaemia research is to advance appropriately.
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