Abstract
From 1993–2001 we treated 186 patients (pts) with relapsed or primary refractory diffuse large B cell lymphoma (DLBCL) on IRB-approved clinical trials with ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy (SLT). Pts with chemosensitive disease received high dose chemoradiotherapy (HDT) and ASCT. In the context of these studies we reported the following: Pts achieving a complete response to ICE, pre-HDT/ASCT, have an improved overall survival (OS) (Journal of Clinical Oncology 1999, 12: 3776–85), pts with chemosensitive primary refractory disease have the same OS as relapsed pts (Blood 2000, 96: 2399–2404); and the second-line age-adjusted IPI (SAAIPI) predicts OS (Blood 2003, 102: 1989–96). In an attempt to further delineate prognostic factors in this setting tissue microarrays (TMA) were constructed as previously described by our group (Hum Pathol 2002: 968–74). All patients had a repeat biopsy prior to initiating SLT confirming active DLBCL; this sample was used for the TMA. Adequate tissue was available on 88 of these pts. TMA sections were stained for the following immunohistochemical markers and analyzed: MIB-1 (Ki-67), MUC1, MDR, p53, bcl-2, CD10, bcl-6, and MUM1. MIB-1 was scored in quartiles and for statistical purposes grouped as 1–2+ (<50% tumor cells positive) and 3–4+ (>50% tumor cells positive). For all other markers, a positive score was based on >20% of tumor cells staining positive. The "molecular phenotype"(MP), germinal center (GC) vs non-GC has an impact on progression-free survival in untreated DLBCL; we also evaluated whether the MP of the pre-ICE biopsy specimen could predict survival in pts with relapsed or primary refractory DLBCL undergoing SLT/HDT/ASCT. A GC phenotype is defined as either CD10 positive or bcl-6 positive and MUM 1 negative (
Conclusion: A non-GC "molecular phenotype" does not predict for a poor outcome in pts with relapsed or primary refractory DLBCL treated with ICE-based SLT followed by HDT/ASCT.
MARKER ANALYSIS FOR 88 PTS WITH RELAPSED/REFRACTORY DLBCL
MARKER . | OVERALL SURVIVAL . | P VALUE . |
---|---|---|
MIB 1 0–2+ | 38.6% | |
MIB 1 3–4+ | 41% | 0.9 |
MUC 1 neg. | 39.2% | |
MUC 1 pos. | 40.6% | 0.5 |
MDR neg. | 34.5% | |
MDR pos. | 40.6% | 0.6 |
p53 neg. | 39.5% | |
p53 pos. | 41% | 0.6 |
Bcl-2 neg. | 37.1% | |
Bcl-2 pos. | 42.2% | 0.9 |
CD10 pos. | 39.7% | |
CD10 neg. | 40% | 0.8 |
bcl-6 pos. | 33% | |
bcl-6 neg. | 44% | 0.5 |
MUM 1 neg. | 36% | |
MUM 1 pos. | 41.8% | 0.8 |
MARKER . | OVERALL SURVIVAL . | P VALUE . |
---|---|---|
MIB 1 0–2+ | 38.6% | |
MIB 1 3–4+ | 41% | 0.9 |
MUC 1 neg. | 39.2% | |
MUC 1 pos. | 40.6% | 0.5 |
MDR neg. | 34.5% | |
MDR pos. | 40.6% | 0.6 |
p53 neg. | 39.5% | |
p53 pos. | 41% | 0.6 |
Bcl-2 neg. | 37.1% | |
Bcl-2 pos. | 42.2% | 0.9 |
CD10 pos. | 39.7% | |
CD10 neg. | 40% | 0.8 |
bcl-6 pos. | 33% | |
bcl-6 neg. | 44% | 0.5 |
MUM 1 neg. | 36% | |
MUM 1 pos. | 41.8% | 0.8 |
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