title: Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation.
abstract: In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by morphology, phenotype, and cytogenetics in the proposed Revised European-American Classification of Lymphoid Neoplasms (REAL), the clinical relevance of which is still debated. We analyzed 670 NHL cases included in two randomized clinical trials (EORTC 20855 WF-intermediate/high-grade and 20856 WF-low-grade malignancy) with histologic material available for review. Based on hematoxylin-eosin-stained sections, 77% of cases could be subtyped. Immunophenotyping was considered to be mandatory only in diagnosing T-cell lymphoma and anaplastic large-cell lymphoma. Of 522 cases subtyped, 11% were mantle cell lymphoma (MCL), 5% were marginal zone B-cell lymphoma (MZBCL), 46% were follicle center lymphoma, and 32% were diffuse large B-cell lymphoma. Statistical analysis and comparisons between classifications were made only within each trial and treatment group. MCL and MZBCL were characterized by a shorter median survival (3.4 and 4.1 years, respectively) in comparison with low- and intermediate-grade WF groups (> 9.3 and 5.8 years, respectively). In terms of progression-free survival, MCL showed a behavior similar to the low-grade group, with frequent relapses. Follicle center cell lymphomas behaved as low-grade lymphomas as defined by the WF and diffuse large B-cell lymphomas as the WF-intermediate grade group. Because several NHL entities have a clinical behavior of their own, their recognition by the REAL classification offers clinicians additional information that is not obtained when the WF is used.
authors.affiliation: Universitaire Ziekenhuizen, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Pittaluga
authors.forename: L
authors.initials: L
authors.lastname: Bijnens
authors.forename: I
authors.initials: I
authors.lastname: Teodorovic
authors.forename: A
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: J H
authors.initials: JH
authors.lastname: Meerwaldt
authors.forename: R
authors.initials: R
authors.lastname: Somers
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: E M
authors.initials: EM
authors.lastname: Noordijk
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D001853:Bone Marrow / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000145:classification* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008466:Mechlorethamine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D011994:Recombinant Proteins; D016019:Survival Analysis; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate