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Annals of Oncology Advance Access originally published online on December 19, 2007
Annals of Oncology 2008 19(3):560-565; doi:10.1093/annonc/mdm520
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© The Author 2007. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

hematologic malignancies

Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2

P. Morel1, P. Gaulard2, C. Gisselbrecht3, C. Ferme4, G. Salles5, H. Tilly6, J. Brière3, M. C. Copin7, P. Lederlin8, O. Hermine9, I. Theate10, C. Haioun11 and N. Mounier3,*

1 Service d'Hématologie Clinique, Hôpital Schaffner, Lens
2 Département de Pathologie, Hôpital Henri Mondor, Assistance Publique—Hopitaux de Paris (AP-HP), Creteil
3 Institut Universitaire d'Hématologie, Hôpital Saint Louis, AP-HP, Paris
4 Département de Médecine, Institut Gustave Roussy, Villejuif
5 Service d'Hematologie Clinique, Hopital Lyon Sud, Pierre Bénite
6 Département d'Hématologie, Centre Henri Becquerel, Rouen
7 Service d'Anatomie et Cytologie pathologique, Centre Hospitalier Regional Universitaire de Lille, Lille
8 Service d'Hematologie et Médecine Interne, Hôpital Brabois, Vandoeuvre les Nancy
9 Service d'Hematologie, Hôpital Necker, AP-HP, Paris, France
10 Département de Pathologie, Université Catholique de Louvain, Brussels, Belgium
11 Service d'Hématologie Clinique, Hôpital Henri Mondor, AP-HP, Creteil, France

* Correspondence to: Dr N. Mounier, Onco-Haematology Department, Hospital l'Archet, 151 Route de Saint Antoine-Ginestière, 06000 Nice, France. Tel: +33-4-92-03-58-41; Fax: +33-4-92-03-58-95; E-mail: mounier.n{at}chu-nice.fr

Background: Overexpression of B-cell lymphoma 2 (bcl-2) protein is a simple biological adverse prognostic factor that could delimit the poor prognosis population candidate for improvement with high-dose therapy and autologous stem-cell transplantation (ASCT) in diffuse large B-cell lymphoma (DLBCL). Therefore, we conducted a risk-adapted phase II study with ASCT as consolidation therapy in low-intermediate risk (LIR) International Prognostic Index patients aged ≤60 years with bcl-2 overexpression (bcl-2+).

Patients and methods: Induction chemotherapy consisted of four courses of adriamycin, cyclophosphamide, vindesine, bleomycin, prednisone, once every 2 weeks. Responding bcl-2+ patients received ASCT as consolidation, and those without bcl-2 overexpression (bcl-2–) conventional chemotherapy. Three hundred and sixteen LIR patients with DLBCL, aged between 18 and 60 years, were included. Of these, 177 (56%) were bcl-2+ and 139 (44%) bcl-2–.

Results: Complete response rates after induction chemotherapy were similar in bcl-2+ and bcl-2– patients (74% versus 78%). Estimated 2-year event-free survival and disease-free survival for the bcl-2+ subgroup were 79% and 87%, for bcl-2– 84% and 92% and for the whole series 81% and 90%, respectively.

Conclusions: These results demonstrate that taking into account biological characteristics in prospective multicenter trials allow successful adjustment of treatment and indicate that ASCT may counteract the adverse prognostic value of bcl-2 overexpression in responding LIR patients.

Key words: autologous stem-cell transplantation, bcl-2, high-dose chemotherapy, lymphoma

Received for publication October 5, 2007. Accepted for publication October 9, 2007.


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