TUMOR-NECROSIS-FACTOR LIGAND-RECEPTOR SYSTEM CAN PREDICT TREATMENT OUTCOME IN LYMPHOMA PATIENTS

Purpose: A prospective study was performed to assess plasma measuremen t of tumor necrosis factor (TNF), lymphotoxin alpha (LT alpha), and th eir soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. Patients and Methods: One hundred f orty-two patients, 124 with Hodgkin's lymphoma (NHL) and 18 with Hodgk in'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 Onco logy Group (ECOG) status greater than or equal to 2, Ann Arbor stage I II/IV, elevated serum lactate dehydrogenase (LDH) and beta(2)-microglo bulin levels, greater than or equal to two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p5 5 and p75 were associated with older age and higher values of C-reacti ve protein. TNF, p55, and p75, but not LT alpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome w ere 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 ra tes were 79%, 60%, and 37%, respectively (P < .0001), and overall surv ival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IP I) yielded a significant improvement of the predictive value of IPI. C onclusion: TNF and its soluble receptors' plasma measurements represen t valuable prognostic markers in lymphoma patients. (C) 1997 by Americ an Society of Clinical Oncology.