MRD evaluation, targeted therapy and stem cell transplantation: how to combine in adult ALL

Summary There exist standard molecular methods of minimal re sidual disease (MRD) evaluation in acute lymphoblastic leukemia (ALL), in order to detect leukemic blast cells (LBC) not assessable by microscopy of bone marrow. The best time point for MRD evaluation and MRD-based treatment stratification in ALL is shown to be ca.14-16 weeks after induction/ consolidation treatment. Reduc tion of MRD load before SCT, as a next step of therapy, is quite desirable. E.g., induction and consolidation treatment with tyrosine kinase inhibitors (NKI) increase the molecular CR rate compared to conventional chemotherapy, as measured by the quantitative RT-PCR assays of bcr/abl fusion oncogene. Failure of treatment by molecular criteria identifies the worst ALL subgroup. Several window studies in ALL with new cytostatic drugs (TKIs or MoABs) were aimed to reduce the tumor load before SCT. Moreover, novel immunotherapeutic approaches include application of monoclonal antibodies against specific surface antigens typical to certain differentiation steps in B-lineage. Hence, evaluation of minimal residual disease is a new parameter for treatment stratification. The conversion of MRD-positivity to MRD-negativity is also a new endpoint for studies. Targeted therapy with TKI has improved the outcome for adult Ph+ ALL patients substantially, evidently by an increased molecular remission rate, and a substantial improvement of survival after SCT. Meanwhile, maintenance with a TKI is recommended after SCT, whereby the optimal duration is so far not known. Maintenance with a TKI is recommended after SCT, whereby the optimal duration is so far not known.