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Blood, 1 December 2002, Vol. 100, No. 12, pp. 3935-3941
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
BCL-2 expression in Hodgkin and Reed-Sternberg cells of classical
Hodgkin disease predicts a poorer prognosis in patients treated with
ABVD or equivalent regimens
George Z. Rassidakis,
L.
Jeffrey Medeiros,
Theodoros P. Vassilakopoulos,
Simonetta Viviani,
Valeria Bonfante,
Gianpaolo Nadali,
Marco Herling,
Maria K. Angelopoulou,
Roberto Giardini,
Marco Chilosi,
Christos Kittas,
Timothy J. McDonnell,
Gianni Bonadonna,
Alessandro M. Gianni,
Giovanni Pizzolo,
Gerassimos A. Pangalis,
Fernando Cabanillas, and
Andreas H. Sarris
From the Departments of Lymphoma-Myeloma,
Hematopathology, and Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston; First Department of Internal
Medicine and Laboratory of Histology and Embryology, National and
Kapodistrian University of Athens, Greece; Departments of Medical
Oncology and Pathology, Istituto Nazionale Tumori, Milan, Italy; and
Departments of Hematology and Pathology, University of Verona, Italy.
To determine the clinical significance of BCL-2 expression in
Hodgkin-Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD),
we correlated its expression with presenting clinical and laboratory
features and failure-free survival (FFS). Eligible patients were
untreated and negative for HIV-1; they had biopsy-proven cHD.
BCL-2 expression was determined immunohistochemically in available
pretreatment tissue biopsy specimens without knowledge of clinical
outcome. Tumors were considered positive if any HRS cells expressed
BCL-2. We identified 707 patients with cHD, whose median age was 30 years; 54% were men. HRS cells expressed BCL-2 in 359 (65%) of 551 nodular sclerosis, 67 (47%) of 143 mixed cellularity, and all 5 lymphocyte depletion. For all patients, the 5-year FFS was 74% versus
84% for tumors with versus without BCL-2 expression (P = .0016, by log-rank test). For the 412 patients
treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
or equivalent regimens, the 5-year FFS for tumors with versus without BCL-2 expression was 74% versus 88% (P = .001, by
log-rank test); for the 233 patients with Ann Arbor stage I or II, FFS
was 84% versus 92% (P = .04, by log-rank test); and for
the 179 patients with Ann Arbor stage III or IV, FFS was 62% versus
81% (P = .006, by log-rank test). Multivariate analysis
confirmed that BCL-2 expression is independently associated with
inferior FFS along with age 45 or older, Ann Arbor stage IV, low serum
albumin and high serum lactate dehydrogenase levels. We conclude that
BCL-2 is frequently expressed by HRS cells in cHD and is associated with inferior FFS in patients treated with ABVD or equivalent regimens.
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