Is measurement of molecular response to therapy in bone marrow useful in children with isolated extramedullary relapse of acute lymphoblastic leukaemia

In a retrospective collaborative study in children with an isolated extramedullary (IEM) relapse of acute lymphoblastic leukaemia, we demonstrated that bone marrow is involved at relapse diagnosis on submicroscopic level and this submicroscopic bone marrow involvement (SBI) revealed a prognostic impact. In a current prospective study in first IEM relapses treated according to the ALL-REZ BFM 2002 trial, SBI has been observed in 72% of patients. Therefore we have been interested, how are the reduction kinetics of SBI during treatment. We have quantified the SBI at relapse diagnosis and its reduction during therapy (MRD) using T-cell receptor/immunoglobulin gene rearrangements in 43 patients (28 central nervous system/10 testicular/5 other extramedullary relapses). 76% of patients who had a positive SBI at relapse diagnosis showed a negative MRD-result after induction. However, MRD reappeared or increased at later time points in 5 patients. These MRD reappearances/increases preceded a subsequent relapse in 3/5 patients. We have developed a common database to combine our data with prospective data of international collaboration partners for a sufficiently large statistical analysis. Deutsche Kinderkrebsstiftung, Bonn Madeleine-Schickedanz Kinderkrebsstiftung, Furth-Dambach