title: 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.
abstract: 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.
authors.affiliation: Department of Lymphoma-Myeloma, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. gzrassidakis@mail.mdanderson.org
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.forename: Simonetta
authors.initials: S
authors.lastname: Viviani
authors.forename: Valeria
authors.initials: V
authors.lastname: Bonfante
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Nadali
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
authors.forename: Roberto
authors.initials: R
authors.lastname: Giardini
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Christos
authors.initials: C
authors.lastname: Kittas
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonnell
authors.forename: Gianni
authors.initials: G
authors.lastname: Bonadonna
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabanillas
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Sarris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin