Results

 
Stem cell harvest and purging
Initially the stem cell support was provided by bone marrow grafts purged with immunomagnetic beads (removing contaminating tumour cells by negative selection). More than 100 patients received purged grafts. The manipulation of the grafts did not harm bone marrow reconstitution, but we were not able to demonstrate a reduction of relapses in the patients who received purged bone marrow grafts. From 1993 – 94 we have used hematopoietic stem cells mobilized from blood after pre-treating the patients with chemotherapy and a hematopoietic growth-factor (G-CSF). Further refinements have been achieved by manipulation of the peripheral stem cell grafts. Compared with bone marrow stem cell support, the time to engraftment was significantly shorter in the patients who received stem cells from blood independent of whether manipulation had been performed or not. Furthermore, the number of infections and transfusions were significantly reduced and the hospitalisation time was shorter.

Clinical results
Close to 400 patients have received HDT at NRH since 1987, approximately 200 of these patients according to various phase II and phase III protocols.

The first phase II studies in Burkitt’s and lymphoblastic lymphomas with HDT in first remission showed statistically significant improved overall survival as compared to historical controls at NRH. The beneficial effect of HDT in lymphoblastic lymphomas was later confirmed by a randomised study where NRH also took part.

In the phase II study of relapsed diffuse large cell lymphomas HDT induced long-term remission (5 year OS) in 40% of the patients, which was significantly better than in the historical controls. These were confirmed in an EBMT survey and also by a prospective randomised study. In primary resistant and chemo sensitive relapsed Hodgkin’s lymphomas the results by HDT are very. Three phase II studies have been undertaken in which different autografts have been employed from bone marrow, blood stem cells and CD 34+ stem cells selected by immunomagnetic beads. The clinical outcome was similar in the three groups with five -year OS in excess of 70%. Blood stem cells and CD 34+ selected stem cells from blood induced faster bone marrow reconstitution.

An important issue has been the significance of HDT in ”low-grade” lymphomas and especially in the follicular subgroup. The risk of tumour cells contaminating the autografts is considerable in these lymphomas. In a European randomized three-armed study of relapsed follicular lymphoma, the effect of HDT with and without purging of the autograft (using our purging procedure) was tested against conventional chemotherapy. The final results showed a benefit of HDT versus conventional chemotherapy, but no benefit of purging could be demonstrated.