CCBIO seminar: Øystein Bruserud
Classification and prognostication of acute myeloid leukemia – the past, the present and the future
Øystein Bruserud, Department of Clinical Science, University of Bergen
Acute myeloid leukemia (AML) is a very aggressive and a very heterogeneous disease. The current initial treatment is highly standardized, whereas the further consolidation treatment is based on a prognostic evaluation of the patients. At the time of diagnosis patients are classified according to the WHO classification system that was revised in 2016. This current classification is based on morphology together with genetics, mainly the karyotyping. Although the classification incorporates important genetic abnormalities with regard to response to treatment, it has a limited value with regard to prognostication of the patients because it is incomplete with regard to genetic abnormalities and does not take into account the response to treatment.
The response to treatment is evaluated in different ways, either (i) remaining morphological signs of leukemia 14-17 days after treatment; (ii) complete remission after one induction cycle; or (iii) minimal residual disease (MRD) in patients reaching complete remission. Thus, the current focus on MRD is a natural development from the previous morphological evaluation of response to treatment. MRD is usually evaluated by PCR or flow cytometry based methods. Despite use of these advanced technologies, and even though results of MRD analysis may indicate an improvement of patient prognostication it has important limitations mainly due to standardization of sampling and whether the collected samples can be regarded as representative. The analysis of remaining leukemic or preleukemic stem cells may represent a future improvement.
AML is a heterogeneous disease, and it is not difficult to argue that every patient has his/her own disease. Another problem is the relatively large number of patients with uncommon genetic abnormalities where the prognostic impact is unknown. Just to make things easy they are classified to have an intermediate prognosis. A major challenge is to clarify whether there are phenotypic similarities across the genetic differences, and whether these phenotypic similarities are suitable as targets for antileukemic treatment. Finally, a major problem is those patients that fail the initial standard treatment and do not reach disease control (i.e. complete hematological remission); we need diagnostic tools to identify these 20-50% of patients before start of treatment. These patients with the most aggressive disease probably need a different treatment from the first cycle and not a different treatment after an initial treatment failure.
Chairperson: Bjørn Tore Gjertsen <email@example.com>, CCBIO