High dose therapy and stem cell research

High dose therapy (HDT) with autologous stem cell support (ASCT) as treatment for cancer has been performed at OUH since 1987. At that time, an institutional strategy for HDT was founded. Initially, the program focused on malignant lymphomas with the most unfavorable outcome at the time, Burkitt lymphoma and lymphoblastic lymphoma.

The indications for HDT-ASCT have been refined by a series of national and international studies, mostly phase 2 but also some randomized phase 3 trials. HDT-ASCT is now offered to relapsed or refractory Hodgkin lymphoma, relapsed high-risk or transformed follicular lymphoma, mantle cell lymphoma, aggressive T-and NK/T-cell lymphoma, lymphoblastic lymphoma and late relapsing diffuse large B-cell lymphoma. The latest addition to the list is consolidation HDT-ASCT in primary central nervous system lymphomas after induction therapy based on the ongoing IELSG-43 trial. Burkitt lymphoma is now rarely treated with HDT-ASCT.

Studies on HDT-ASCT in adjuvant treatment in localized breast cancer with high risk, small cell lung cancer, Ewing sarcomas, osteosarcomas and testicular cancer have been done during the 1990ies and early 2000s. 

Since 2015, studies have been undertaken to possibly replace HDT-ASCT by less intensive treatment, thus reducing the chemotherapy burden for patients. The most notable examples are our participation in the Triangle study, evaluating the possibly substitution of HDT-ASCT by Ibrutinib, an inhibitor of Bruton Tyrosin Kinase and the Euronet-PHL-C1 relapse study for children and adolescents with classical Hodgkin lymphoma. The latter evaluated omission of HDT-ASCT for certain low risk patients with relapse of Hodgkin lymphoma.

The landscape of HDT-ASCT is continuously evolving, no also by expanding participation in studies involving chimeric antigen receptor (CAR) T-cells.

Studies ongoing:

IELSG-43Study. High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma – randomized phase III trial (MATRix). Enrolment complete IELSG – International Extranodal Lymphoma Study Group

Triangle-Study. Autologous transplantation after a rituximab/ ibrutinib/ Ara-C containing induction in generalized mantle cell lymphoma – a randomized European MCL network. Enrolment complete. ctc.ucl.ac.uk/TrialDetails.aspx?Trial=133&TherA=4