Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.
OBJECTIVE
A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas.


METHODS
One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA).


RESULTS
Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI.


CONCLUSIONS
TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.
Warzocha
K
K
Service d'Hématologie and Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Lyon, France.
Salles
G
G
Bienvenu
J
J
Bastion
Y
Y
Dumontet
C
C
Renard
N
N
Neidhardt-Berard
E M
EM
Coiffier
B
B
D015703:Antigens, CD / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008223:Lymphoma / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D008233:Lymphotoxin-alpha / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012306:Risk; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008233:Lymphotoxin-alpha; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha