Diffuse large B cell lymphoma (DLBCL) is the most common types of
non-Hodgkin’s lympoma. Approximately half of all patients (pts) will be
cured of their disease by primary therapy. Two major subgroups were
identified by gene expression profiling: germinal centre B (GC) cell or
non-germinal centre (non-GC). The GC group showes a significantly
better survival than the non-GC group. Immunohistochemistry has been
evaluated as a surrogate for this molecular classification. The aim of this
study was to define retrospectively the B-cell origin of 40 pts treated
with R-CHOP14 and to evaluate if the dose-dense therapy could
improve clinical outcome. We performed a centralized immunohistochemical stains on formalin-fixed paraffin-embedded tissues from diagnostic biopsies with the following antibodies: CD10, bcl-6, bcl-2, MUM1
and Mib1. Based on the published algorithm we subdivided the pts in
GCB and non-GCB origin. We evaluated also the prognostic value of single protein expression. Twenty-seven pts were male, 22 stage III-IV, 17
presented symptoms at diagnosis 22 showed abnormal LDH value, the
IPI was intermediate-high risk or high risk in 13 pts. According to
immunohistochemistry analysis 16 pts derived from GC and 24 from
non-GC, 12 pts presented a positive CD10, 30 a positivity for bcl6, 19
a positive bcl2 and 27 a positive MUM1. Twenty-nine pts (73%)
obtained a complete remission (CR), 8 a partial response (PR) and 3 were
non responders (NR). Four out 29 CR pts experienced relapse, three
(75%) derived from nonGC. Eight pts died, 4 derived from GC and 4
from non-GC. After a median period of observation of 18 months (range
3-72) the overall survival (OS) was 75% and the failure free survival
(FFS) was 57%. The statistical analysis was performed comparing the B
cell origin and clinical characteristics, moreover was also evaluated the
expression of bcl2 either in GC or in non-GC lymphomas. In univariate
analysis normal Beta2 microglobulin and low-intermediate risk IPI were
significantly associated with longer overall survival. In univariate and
multivariate analysis FFS was significantly higher in low and low-intermediate IPI risk pts. No differences were reported in OS and FFS evaluating the B cell origin. In conclusion we can point out that the intensification could enhance the efficacy of R-CHOP regimen improving the
overall survival and FFS in pts with non-GC lymphoma. In this analysis
the only significance was the IPI index that affected either OS or FFS
