Factors that predict chemotherapy-induced myelosuppression in lymphoma patients: Role of the tumor necrosis factor ligand-receptor system

Purpose: To analyze factors that predict the occurrence of chemotherapy-ind uced myelosuppression and, in particular, the role of the tumor necrosis fa ctor (TNF) ligand-receptor system in lymphoma patients at the beginning of their treatment. Patients and Methods: We investigated the predictive factors for myelosuppr ession after the first course of chemotherapy in a cohort of 101 consecutiv e, previously untreated lymphoma patients receiving regimens that include d oxorubicin and cyclophosphamide. Plasma samples were tested at baseline by enzyme-linked immunosorbent assay for TNF and its soluble receptors. Univar iate and multivariate analyses were performed with a forward regression pro cedure that included all of the parameters that were found to be significan t in the univariate analysis. The dose of chemotherapy and the prophylactic treatment with granulocyte colony-stimulating factor were deliberately inc luded in this model. Results: Sixty-seven patients experienced World Health Organization (WHO) g rade 4 neutropenia, and 37 patients experienced febrile neutropenia, which was responsible for WHO grade 2 through 4 infections in 23 patients. In mul tiparametric regression analysis, the occurrence of grade 4 neutropenia was associated with high doses of cyclophosphamide (odds ratio [OR], 19.8; P = .008) and high levels of soluble p75-R-TNF (OR, 8.52; P = .001). The durat ion of grade 4 neutropenia for more than 5 days was associated with the lac k of hematopoietic growth factor administration (OR, 6.76; P = .004) and hi gh levels of soluble p75-R-TNF (OR, 5.84; P = .0023). The occurrence of feb rile neutropenia was associated with high doses of cyclophosphamide (OR, 4. 7; P = .007), altered performance status (OR, 18.8; P < .0001) and high lev els of soluble p75-R-TNF (OR, 3.49; P = .029). Conclusion: This study indicates that in addition to the dose of chemothera py and the administration of hematopoietic growth factors, poor performance status and high p75-R-TNF levels can predict the occurrence of chemotherap y-induced myelosuppression in lymphoma patients. This model may help in sel ecting patients for prophylactic growth factor administration. (C) 2000 by American Society of Clinical Oncology.