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Prognostic relevance of serum ß2 microglobulin in patients with follicular lymphoma treated with anthracycline-containing regimens. A GISL study

From Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena (MF, SL, CM, LM, MoB, SP); Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza", II Facoltà di Medicina e Chirurgia, Roma (CG, SB); Cattedra di Anatomia Patologica, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, A. O. S. Paolo e Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano (UG); Dipartimento Integrato Servizi Diagnostici e di Laboratorio, Università di Modena e Reggio Emilia, Modena (AM); Unità Operativa di Ematologia, A.O. S. Maria Nuova, Reggio Emilia (FM); Divisione di Ematologia, Azienda Ospedaliera "Bianchi-Melacrino-Morelli", Reggio Calabria (CS); Dipartimento di Oncologia ed Ematologia, Ospedale Guglielmo da Saliceto, Piacenza (AL); Medicina Interna, Oncologia Medica, Università di Pavia, IRCCS Policlinico S. Matteo, Pavia (PGG); Unità Malattie Linfoproliferative, Dipartimento di Ematologia, Centro G. Marcora, Ospedale Maggiore, IRCCS, Milano (LB); U. O. Oncologia Medica I, IRCCS, Fondazione Salvatore Maugeri, Pavia (VF); Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina (MaB)

Correspondence: Massimo Federico, MD, Dipartimento di Oncologia ed Ematologia, Centro Oncologico Modenese, Università di Modena e Reggio Emilia, Policlinico, Via del Pozzo 71, 41100 Modena, Italy. E-mail: federico{at}unimore.it

Background and Objectives: Although serum ß2 microglobulin (ß2 M) is an easy parameter to measure, and over-expressed in a large number of lymphoproliferative diseases, its prognostic value has been largely underestimated. The present study examined the influence of ß2M levels on overall survival (OS) of patients with follicular lymphoma (FL).

Design and Methods: The prognostic role of ß2M was evaluated in 236 patients with FL identified from the databases of the Gruppo Italiano per lo Studio dei Linfomi (GISL) and treated with anthracycline-based regimens from 1993 to 2003.

Results: Elevated serum ß2M levels were found in 82 patients (35%). According to multivariate logistic regression analysis, elevated ß2M levels were associated with elevated lactate dehydrogenase (LDH) (p=0.021), age (p=0.029), and number of involved nodal areas (p<0.001). The percentage of elevated ß2M levels increased progressively with increasing FLIPI scores (17%, 38%, and 63% in the low-, intermediate-, and high-risk groups, respectively). Five-year OS was 61% (95% CI, 47–73%) and 89% (95% CI, 82–93%) for patients with elevated vs normal ß2M levels respectively (p<0.001). Cox regression analysis showed that ß2M level had an independent and stable prognostic value (HR=3.0; 95%CI, 1.6–5.7). In a multivariate analysis the impact of ß2M level on survival was independent of FLIPI score, with a HR of 2.94 (95% CI, 1.54–5.62).

Interpretation and Conclusions: Our results demonstrate that in patients treated in the pre-rituximabera, ß2M level was an independent prognostic marker in addition to FLIPI score. We thus suggest that ß2M be routinely assessed and tested in future prognostic studies of FL patients treated with combination chemotherapy and anti-CD20 agents.

Key words: ß2 microglobulin, follicular lymphoma, GISL, prognosis, survival.

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