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Binet’s Staging System and VH Genes Are Independent but Complementary Prognostic Indicators in Chronic Lymphocytic Leukemia

Yuri Vasconcelos, Frédéric Davi, Vincent Levy, Pablo Oppezzo, Christian Magnac, Ariane Michel, Mihoko Yamamoto, Otto Pritsch, Hélène Merle-Béral, Karim Maloum, Florence Ajchenbaum-Cymbalista, Guillaume Dighiero

From the Institut Pasteur; Hôpital Pitié-Salpêtrière; Biostatistique, Unité L’Institut National de la Santé et de la Recherche Médicale 444 Hôpital St Louis; Hôtel-Dieu, Paris, France; Disciplina de Hematologia e Hemoterapia-Universidade Federal de São Paulo, São Paulo, Brazil; and Hospital Maciel, Facultad de Medicina, Montevideo, Uruguay.

Address reprint requests to Guillaume Dighiero, MD, Unité d’Immuno-Hématologie, et d’Immunopathologie, Institut Pasteur, 28 Rue du Docteur Roux, 75015 Paris, France; e-mail: dighiero{at}pasteur.fr.

Purpose: Rai’s and Binet’s staging systems have contributed significantly to the identification of major prognostic groups in chronic lymphocytic leukemia (CLL), though they fail to accurately predict disease progression at the individual level. Biologic factors, such as the mutational status of the immunoglobulin heavy-chain variable genes (VH, cytogenetics, CD38 expression, and some serum markers, have recently improved prognostic assessment in CLL. In this study, we analyzed the prognostic value of VH mutational status within the different stages of Binet’s classification in 145 patients.

Patients and Methods: Our series consisted of 83 VH mutated (MT) and 62 VH unmutated (UM) patients. MT cases predominated within Binet’s stage A (70%), whereas UM cases predominated among stages B and C (62%).

Results: Median overall survival (OS) was 84 months for UM patients and was not achieved for the MT group (70% 12-year survival, P < .0001). Concerning Binet’s stage A, both median OS and progression-free survival were significantly shorter for UM patients when compared with those of MT patients (97 months v not achieved, P = .0017; and 42 v 156 months, P < .0001), which compared favorably with the classical A' and A'' substaging. The VH mutational profile could also segregate stage B and C patients into two groups with different survival patterns (median OS, 78 v 120 months for UM and MT patients, respectively; P = .002).

Conclusion: The significant survival differences observed between the VH mutational groups, among stage A and stage B and C patients, indicate that Binet’s classification and VH genes are independent prognostic variables and are most likely complementary.

Supported in part by a fellowship from the Brazilian government agency CAPES (Y.V.).

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