Effect of radioimmunotherapy-based conditioning for autologous stem cell transplantation on poor-risk molecular profiling in diffuse large B-cell lymphoma.

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6547 Background: Gene expression profiling has improved risk stratification of diffuse large B-cell lymphoma (DLBCL) in the first line setting as shown by DNA microarray analysis and immunohistochemistry (IHC). 5-year overall survival (OS) for germinal center B-cell-like (GCB) DLBCL is significantly better than that for non-GCB DLBCL in newly diagnosed patients. However, in the relapsed/refractory setting, autologous stem cell transplant (ASCT) appeared to overcome the poor prognosis of cell of origin as defined by IHC using CD10, Bcl6 and MUM1 and there was no difference in survival between GCB and non-GCB groups. Ibritumomab tiuxetan (Z)-BEAM conditioning regimen for ASCT in DLBCL has produced promising response rates and progression free survival (PFS). The role of poor risk molecular markers in predicting outcome with the novel conditioning regimen Z-BEAM is unknown. Methods: We evaluated cell of origin (GCB, non-GCB) using IHC in 36 patients undergoing ASCT with Z-BEAM conditioning from 2002 to 2010. Median age of the patients was 54.5 years. There were 12 females and 24 males. 6 patients were in 1st CR/PR ( 17%), 12 had induction failure disease (33%), 9 were in 1st relapse (25%), 1 in 2nd relapse (3%) and 8 were in ≥2nd CR (22%). 27 patients had chemosensitive disease (75%) and all had prior rituximab exposure. Median number of prior treatments was 2. IPI at transplant was mainly low risk (78%). 22 patients had GCB (61%) and 14 (39%) had non-GCB DLBCL. Results: Median follow up is 25.6 months. 12 patients relapsed (33%) and 9 died (25%). The major cause of death is relapse/disease progression. At 2 years, median OS is 79% and median PFS is 64%. No significant difference in 2 year OS and PFS is noted between the GCB and non-GCB groups (p=0.07 and 0.06 respectively). Conclusions: Z-BEAM conditioning for ASCT may overcome the poor prognostic effect of non-GCB DLBCL in relapsed/refractory disease. Further evaluation of cell of origin using new markers like GCET1, LMO2 and FOXP1 could confirm these results as there seems to be better concordance of these markers with DNA microarray analysis.