I know that Dr Crippen and Dr Rant hate checklists and flowcharts guiding them through diagnoses but in clinical trials they are necessary to obtain standardisation between participating centres and thus statistically relevant data – I am sure that Dr Crippen and Dr Rant will agree.
In the UKALL 2003 trial there is an initial diagnosis flowchart by which patients are allocated to the three treatment regimes being compared. Below I partially reproduce this up to the point where Kezia, at Day 8, was allocated to the most intense regimen.
Once our consent had been obtained to participate in the trial, the oncologists and haematologists are not obliged to follow the regimen strictly – if something is amiss, then they will, to the best of their judgement and with the parents’ consent, try non-regimen treatment. This has been the case with our friend’s teenage daughter, H., who seems to have gone through every drug side-effect in the book.However, it was pointed out to us in the first week that there is little difference between an established protocol and the trial protocol – especially with Regime C which is a typically aggressive treatment not based on the level of Minimum Residual Disease, used partly to choose between the less-aggressive treatments of Regimens A and B (but which also take into account bloodcounts etc), but solely on the traditional clinical measurements based on bloodcounts and genetic abnormalities.
Regimens B and C during the first 28 days are the same but differ later.Kezia’s path through the flowchart is in bold.
Under 12 months ? → yes → Interfant trial
BCR-ABL ? → yes → Regimen C
MLL rearrangement ? → yes → Regimen C
Hypodiploid → yes → Regimen C
(≤ 44 chromosomes) ?
AML1 amplification ? → yes → Regimen C
≥ 10 years ? → yes → Regimen C
White Blood Count → yes → Regimen B
≥ 50 x 109/L
Marrow morphology at day 8/15
If on Regimen B, aged 1-15 years: → yes → Regimen C
> 25% blasts (M3) at day 8 ?