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relapsedandrefractoryDLBCL,withpromisingresults(90Yttriumibritumomabtiuxetan: 1 68,107). Considering the effectiveness of RIT in FL, in terms of prolonging PFS (108,109),
it might be a valuable addition to treatment of TFL patients. In chapter 5 (only first
line treatment) and 6 (both first line and second line treatments) we demonstrate the
effectiveness of consolidation with ASCT adding 90Yttrium ibritumomab tiuxetan to BEAM.
In relapse setting (mostly heavily pretreated) TFL patients have been treated with radioimmunotherapy as monotherapy. Response rates and duration of response are less pronounced as described in FL. Overall response rates (ORR) of up to 60% lasting 10-15 months have been found with 90Yttrium ibritumomab tiuxetan as monotherapy (65,110,111). A similar ORR of 60-80% with remission durations of 10 months to 1.3 years has been described with131Iodine-tositumomab (59,60,64,112).
Other treatments and novel targets
Other treatments than the above-mentioned treatment regimes have been studied mostly in phase 1 or 2 studies, in patient groups with heterogeneous histology, and in heavily pretreated patients. Most data are available about the value of lenalidomide, with promising ORR of 45-60% inTFL patients (43,51,52 table 1).
There is a clear need for new targets to treat refractory patients with TFL. In chapter 8 we investigate survivin, a member of the family of inhibitor of apoptosis proteins as a possible target for therapy. We focused on survivin because we found a significantly higher survivin expression in TFL than in FL. This might be a cause for refractoriness of TFL as high expression in aggressive lymphoma has been found to be associated with resistance to therapy and poor outcome (113-115). The small molecule survivin inhibitor YM155 has shown promising results in refractory DLBCL patients in phase II studies (116,117) and we tested YM155 on TFL cell lines and patient samples.
Treatment of TFL: current practice in the Netherlands
Given that there is currently no standard treatment for TFL, as described above, we investigated Dutch practice of TFL treatment over the last decade as described in chapter 4 of this thesis. Additionally we sent an email questionnaire regarding treatment policy to all members of the HOVON lymphoma working group. Members from 17 hospitals, including all 8 academic medical centers responded (response rate 75%). Of the 8 academic medical centers 3 advised R-chemo only, 3 advised up-front consolidation with autologous stem cell transplantation (ASCT), in one center preceded by 90Yttrium ibritumomab tiuxetan, within a clinical study, in one center R-chemo was only followed
Introduction and scope of this thesis
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