T-cell acute lymphoblastic leukemia (T-ALL) is a rare aggressive hematological malignancy that is
characterized by the diffuse infiltration of the bone marrow by malignant T-cell progenitors. Due to the
introduction of intensified combination chemotherapy, the prognosis of T-ALL has significantly improved
over the last years, with current protocols reaching cure rates over 80% in children and about 50% in
adults. Nonetheless, the outcome of patients with primary therapy resistant or relapsed disease remains
extremely poor, with no alternative therapeutic options. Further intensification of the therapy is not an
option due to the already maximal high short- and long-term adverse side effects associated with the
intensive chemotherapy regimens that have already been applied. Here, we aim to setup a pipeline for
functional ex vivo (combination) drug testing on primary samples of refractory/relapsed (R/R) adult TALL patients. In addition, by combining the results of these drug responses with integrated genomics
and transcriptomics data, we aim 1) to get molecular insights in therapy resistance and 2) to identify
biomarkers predicting efficacy of salvage combination therapies. Finally, we will evaluate the efficacy of
these novel salvage therapies in vivo using patient-derived xenograft (PDX) models.