High dose therapy and stem cell research

Strategy since 1987

High dose therapy with stem cell support (HDT) in cancer has been performed at NRH since 1987. At that time, an institutional strategy for HDT was founded. It was decided to focus on malignant lymphomas with an unfavourable clinical course. As a part of the strategy a research project was undertaken for the removal of contaminating lymphoma B-cells from the harvested cell suspensions from the bone marrow. A clinically scaled purging project was developed in order to remove contaminating B- and T- lymphoma cells by means immunomagnetic beads conjugated with monoclonal antibodies directed towards various B- or T- cell antigen determinants on the lymphoma cells.

Thus, the initial project had two aims:

The clinical outcome after HDT in malignant lymphoma.
The effect of purging with immunomagnetic beads with regard to clinical relapse and possible negative effects on engraftment of the bone marraow.

Clinical phase II studies were initiated in relapsed high-grade non-Hodgkins lymphomas and as first line treatment in Burkitts and lymphoblastic lymphomas, both situations with a short median survival (less than 18 months) and with very few patients achieving long-term survival. The reasons for selecting these groups of patients were that the majority of the patients still would have a chemo sensitive disease upon conventional chemo-/radiotherapy and improvement of survival could be detected in these aggressive lymphomas.

During the 1990s, the program has been expanded to comprise relapsed Hodgkins lymphomas, transformed follicular lymphomas and mantle cell lymphomas, as adjuvant treatment in localized poor prognoses breast cancer, small cell lung cancer, Ewing sarcomas, osteosarcomas and testicular cancer. Many of these studies have been undertaken in national or international multicentre cooperation in order to obtain consensus about the clinical benefit of HDT.