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MRD and clonal relations in relapsed acute lymphoblastic leukaemia

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Heterogeneity of molecular response to treatment in a selected subgroup among ALL-relapses

T-cell receptor/Immunglobulin (TCR/IG) gene rearrangements belong to specific clonal markers of acute lymphoblastic leukaemia (ALL) cells which can be identified on genomic level. We have used these markers of clonal leukaemic cell populations for the highly sensitive identification of residual leukaemic cells during treatment (MRD, mininal residual disease) in order to describe the kinetics of leukaemic cell reduction and finally the direct response to treatment.

Our further major focus of investigation is the usage of TCR/IG gene rearrangements beside other genetic changes in order to describe clonal relations of different cell populations.

Using this methodical approach, we have been aming to learn more about the development and the progress of the disease during and after treatment.

The assessment of MRD for risk stratification has been integrated in the current treatment protocol ALL-REZ BFM 2002. The early molecular response to treatment has been used in patients with an intermediate prognosis in order to decide about later treatment intensity: stem cell transplantation or continuation of polychemotherapy. In high risk relapse patients, we have been assessing MRD 'online' at defined time points before stem cell transplantation aiming a treatment intensification according to the speed of leukaemic cell reduction.

The different response to treatment in children with ALL-relapse is probably due to a combination of causes, which have been in our research interest. We expect that these causes consist of characteristics of leukaemic cells and their progenitor cells, their microenvironment and the genetic predisposition.

We perform the systematic assessment of the response to treatment and treatment accompanying research in context of the treatment of children with ALL-relapse as reference laboratory for moleculargenetics and tumorbanking of the ALL-REZ BFM 2002 trial.

Our projects are based on different national and international collaborations.