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Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas

¹ Université de Lyon-Centre Léon Bérard, Department of Medical Oncology and EA SIS 4128, Lyon, France; ² Université de Lyon-Centre Léon Bérard, Department of Statistics, Lyon, France; ³ European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium; ⁴ Institut Gustave Roussy, Villejuif, France; ⁵ Royal Marsden Hospital, London, United Kingdom; ⁶ Erasmus University Medical Center, Rotterdam, The Netherlands; ⁷ Leiden University Medical Center, Leiden, The Netherlands; ⁸ UJOMM, Hopital Edouard Herriot, Lyon, France; and ⁹ Institut National de la Santé et de la Recherche Médicale U590, Centre Léon Bérard, Lyon, France

Requests for reprints: Isabelle Ray-Coquard, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France. Phone: 33-478782888; Fax: 33-478782716; E-mail: ray{at}lyon.fnclcc.fr.

Key Words: cancer • prognosis

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non–Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of <1,000/µL before treatment was constant among the series: 25%, 24%, and 27%, respectively. Lymphopenia was significantly more frequent (P < 0.05) in metastatic breast cancer patients with performance status (PS) of >1, non–Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. Inunivariate analysis, lymphopenia of <1,000/µL significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P < 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P < 0.01), and non–Hodgkin lymphoma (median, 11 versus 94 months; P < 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3–2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0–2.1) along with liver metastases, lung metastases, and PS; and in non–Hodgkin's lymphoma (RR, 1.48; 95% CI, 1.03–2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. [Cancer Res 2009;69(13):5383–91]