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.
OBJECTIVE
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.


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 10(9)/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 10(9)/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).


CONCLUSIONS
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.
Schmidt
Henrik
H
Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark. hesch@as.aaa.dk
Suciu
Stefan
S
Punt
Cornelis J A
CJ
Gore
Martin
M
Kruit
Wim
W
Patel
Poulam
P
Lienard
Danielle
D
von der Maase
Hans
H
Eggermont
Alexander M M
AM
Keilholz
Ulrich
U
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D016019:Survival Analysis; D014481:United States
D014408:Biomarkers, Tumor