Page 22 - Wondergem

Chapter 1
Two large comparative cohort studies reported a significantly better OS after ASCT, albeit only slightly better than the survival after R-chemo only. (Ban Hoeffen 2 yr OS 74% after ASCT vs 59% after R-chemo only, Da villa 5 yr 65% vs 61%, respectively, ref. 35,38). An important observation from these studies was that previous treatment of FL negatively influenced prognosis. This might be the group of patients benefitting from ASCT, since it has been reported that, when treated with R-chemotherapy only, treatment-naïve patients did much better than patients previously treated for FL (2 yr OS 81% vs 39%). This difference in survival was not observed when up-front ASCT was applied (35). In order to find additional evidence for this, the outcome of different treatment regimes in the Netherlands is described in chapter 4.
Allogeneic SCT
There is currently no role for allogeneic SCT as first line treatment, as Da Villa showed inferior survival with alloSCT in first line (38). Considering the increased morbidity, the negative impact on the quality of life in survivors of alloSCT (102,103) and the reasonable OS (5 year 60-75%) in patients reaching CR after induction with R-chemo only or with additional up-front ASCT, alloSCT will not be the preferred first line treatment. Additionally, the substantial TRM (around 20%) does not appear to outweigh any benefit conferred by a reduction in relapse rate (35,38,104).
Since relapse is still the major cause of death, even after autologous SCT, allogeneic SCT, with the potential benefit of a graft-vs-lymphoma effect can be considered for the treatment of relapsed TFL (89,97,105). The main problem with relapsed and refractory patients is that for an alloSCT to be successful, the disease has to be chemosensitive in order to reach preferably a complete remission allowing time for a GVL effect following allogeneic SCT (7,106). This is confirmed by our results of allogeneic SCT in patients with chemo-sensitive TFL, FL and aggressive lymphoma, as described in chapter 7.
Radioimmunotherapy
Radioimmunotherapy (RIT) is defined as therapy with monoclonal antibodies conjugated with a radioactive isotope to target radiation directly to tumor cells, thereby limiting radiation to non-target organs. Both 90Yttrium ibritumomab tiuxetan (Zevalin®) and 131Iodine-tositumomab (Bexxar®), targeting the CD20 surface antigen, have been studied in TFL patients. RIT might be suitable to circumvent rituximab resistance or to eradicate the chemo-refractory cancer (stem-) cell by the so-called crossfire effect (irradiation of surrounding non-CD20-postive cells due to tissue penetration of several millimeters by β particles). RIT has been added to high dose therapy and ASCT in
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