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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1136-1143
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Germinal center phenotype and bcl-2 expression combined with
the International Prognostic Index improves patient risk
stratification in diffuse large B-cell lymphoma
Sharon L. Barrans,
Ian Carter,
Roger G. Owen,
Faith E. Davies,
Russell D. Patmore,
Andrew P. Haynes,
Gareth J. Morgan, and
Andrew S. Jack
From the Hematological Malignancy Diagnostic Service,
Academic Unit of Hematology and Oncology, Leeds General Infirmary,
Leeds, United Kingdom; Hematology, Nottingham City Hospital,
Nottingham, United Kingdom; Hematology, Hull Royal Infirmary, Hull,
United Kingdom.
The International Prognostic Index (IPI) identifies poor- and
good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an
uncertain prognosis. To determine whether cellular factors can be
combined with the IPI to more accurately predict outcome, we have
analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and
a germinal center (GC) phenotype (defined by expression of bcl-6 and
CD10). P53 gene band shifts were detected using
single-stranded conformational polymorphism polymerase chain reaction
analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P < .0001) and
bcl-2 (R = 0.14, P = .0001) were independent poor
prognostic factors and a GC phenotype predicted a favorable outcome
(R =  0.025, P = .02). Neither p53 expression
nor band shifts had a significant effect on survival. Using the IPI
alone, 8% of patients were identified as high risk. Expression of
bcl-2 in the intermediate IPI group identified a further 28% of
patients with an overall survival comparable to the high IPI group. In
the intermediate IPI, bcl-2 group, the presence of a GC
phenotype improved overall survival to levels approaching the IPI low
group. Following this analysis only 15% of patients failed to be
assigned to a favorable- or poor-risk group. Sequential addition of
bcl-2 expression and GC phenotype into the IPI significantly improves
risk stratification in DLBCL. For the 36% of high-risk patients with a
2-year overall survival of 19%, alternative treatment strategies
should be considered in future trials.
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