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Pretreatment Levels of Peripheral Neutrophils and Leukocytes As Independent Predictors of Overall Survival in Patients With American Joint Committee on Cancer Stage IV Melanoma: Results of the EORTC 18951 Biochemotherapy Trial

Henrik Schmidt, Stefan Suciu, Cornelis J.A. Punt, Martin Gore, Wim Kruit, Poulam Patel, Danielle Lienard, Hans von der Maase, Alexander M.M. Eggermont, Ulrich Keilholz

From the Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium; Department of Medical Oncology, University Medical Centre, Nijmegen; Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Royal Marsden Hospital, London; Cancer Research UK Clinical Center, St James' University Hospital, Leeds, United Kingdom; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; and Department of Medicine III, Charité, Campus Benjamin Franklin, Berlin, Germany

Address reprint requests to Henrik Schmidt, MD, Department of Oncology, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark; e-mail: hesch{at}as.aaa.dk

Purpose: An elevated count of blood neutrophils and monocytes recently was shown independently to predict short survival in patients with stage IV melanoma undergoing interleukin-2–based immunotherapy. In this study, we aimed to validate this finding in a large cohort of stage IV melanoma patients.

Patients and Methods: For this retrospective prognostic study, the data from the European Organisation for the Research and Treatment of Cancer 18951 study were used. Patients were randomly assigned between treatment with dacarbazine, cisplatin, and interferon alfa with or without interleukin-2. Counts of neutrophils and leukocytes were analyzed together with other known prognostic factors: serum lactate dehydrogenase, performance status, metastatic site, and sex. Two multivariate prognostic factor analyses were carried out in the model: one with leukocyte counts and one with neutrophil counts.

Results: A total of 363 patients were randomly assigned and baseline blood neutrophil and leukocyte counts were available from 316 and 350 patients, respectively. A high neutrophil count (> 7.5 x 10⁹/L) was an independent prognostic factor for short overall survival (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = 0.02), and a high leukocyte count (> 10 x 10⁹/L) was an independent prognostic factor of both short overall survival (HR, 1.7; 95% CI, 1.3 to 2.4; P = 0.0005) and short progression-free survival (HR, 1.5; 95% CI, 1.1 to 2.1; P = 0.008).

Conclusion: A high pretreatment count of neutrophils in blood was confirmed as an independent prognostic factor for short overall survival in stage IV melanoma patients undergoing interleukin-2–based immunotherapy. Furthermore, a high count of leukocytes was an independent prognostic factor for short overall survival and progression-free survival. Both parameters should be useful as stratification factors in clinical trials.

Supported by Educational grants from Chiron BV, Amsterdam, the Netherlands; Schering-Plough, Kenilworth, NJ; and Grants No. 2U10 CA11488-25 through 5U10 CA11488-36 from the National Cancer Institute, Bethesda, MD.

The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

H.S. and S.S. contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.