Epidemiology data for acute myeloid leukaemia and the ALESE study

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Published: 10 Dec 2017
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Dr James Foran - Mayo Clinic Florida, Jacksonville, USA

Dr Foran speaks with ecancer at the 2017 ASH annual meeting about the ALESE study of intensive therapy in older adults with newly diagnosed acute myeloid leukaemia. The ALESE study documents the ability to collect epidemiology data within a clinical trial, and establishes the prevalence of important clinical epidemiologic exposures associated with leukaemia development in older acute myeloid leukaemia patients in a randomised study population.

 

We’ve been interested in epidemiology. There has been little done in clinical epidemiology in patients with AML. It’s been one of those pressing and needed things for patients and for the community but it really hasn’t been studied within diseases themselves. In the past ASH and even ASCO have not had a big emphasis on epidemiology.

We had some data of our own showing that in some cases what causes your leukaemia might influence the phenotype of your leukaemia or the outcome afterwards so we did a prospective study. ALESE represents that prospective study, so it’s a questionnaire, it’s the Acute Leukaemia Epidemiology and Survival Endpoints questionnaire, and we put it into a prospective therapeutic clinical trial so that all patients got the same therapy, all patients are well described and the outcomes are well controlled. We are collecting data that just hadn’t been collected before about risk factors for leukaemia and to look and see does that correlate with the phenotype, the cytogenetics in this case, or the outcome of their leukaemia. This had not been done before in a leukaemia study. We had almost 60% of patients who were eligible fill in this questionnaire which is a big thing, it is over 100 questions, it takes about 20 minutes to complete. We built a database for it and we’ve just started to analyse that, looking at the cytogenetics as the endpoint. So the question we’re asking is are there particular exposures that might have predisposed to leukaemia which are associated with a cytogenetic risk group in acute myeloid leukaemia and we found in some cases there are.

It’s going to help us understand risk factors for leukaemia better, the phenotype and help us work back towards leukaemogenesis, that’s a grand goal but that’s our ultimate goal. In this trial, it was a large clinical trial, only a subset filled in the questionnaire but we will be doing detailed genotyping of these patients off samples that we’ve collected so we’ll be able to start asking questions, simple questions – do smokers get a different leukaemia than non-smokers? Do people with obesity get a different leukaemia or have a different outcome than people who don’t? Are there other rare risk factors or familial family history of leukaemia that contributes to that? So we’re trying to get after something that’s deeply relevant to patients, missing in the community and, frankly, low-hanging fruit because we just put in a clinical questionnaire to ask about their medical history to capture that, something that hadn’t been done before.

Can you give me a bit more info on what these risk factors, you mentioned a couple there, what are standing out?

We looked at information that you might ask a patient about but you wouldn’t capture in a clinical trial, so simple things about family history and smoking and occupation. We looked at weight at different time-points throughout somebody’s life, this is all self-reported. We tried to get into more detail about occupation, for instance were they working with radioactive materials regularly or did they have a history of that? Or with industrial hydrocarbons or with agricultural chemicals. Smoking, obviously, and then some of their medical history. We were interested in things that might predispose to leukaemia like inflammatory bowel disease which is an unappreciated contributor to acute myeloid leukaemia. Then, obviously, if they’d had a previous cancer the kind of treatments they’d had for that, that’s more well described. So we did find that some of these occupational exposures were significantly associated with specific cytogenetic risk groups. That’s kind of a macro level. We want to know are there cytogenetic lesions associated with this in acute myeloid leukaemia patients but we now want to start drilling down more deeply, and that’s our plan in the next two years, at the actual sequencing data. We have some of our own preliminary data that I’m presenting tomorrow from Mayo Clinic from our own epidemiology cohort but we want to see if that’s confirmed and if that translates. So this is the first prospective effort to do that.

Anything else important to mention?

No, thank you very much. It’s the sort of thing that you would think had been studied and hasn’t so we thought this was the right opportunity to do it.