Factors that predict chemotherapy-induced myelosuppression in lymphoma patients: role of the tumor necrosis factor ligand-receptor system.
OBJECTIVE
To analyze factors that predict the occurrence of chemotherapy-induced myelosuppression and, in particular, the role of the tumor necrosis factor (TNF) ligand-receptor system in lymphoma patients at the beginning of their treatment.


METHODS
We investigated the predictive factors for myelosuppression after the first course of chemotherapy in a cohort of 101 consecutive, previously untreated lymphoma patients receiving regimens that include doxorubicin and cyclophosphamide. Plasma samples were tested at baseline by enzyme-linked immunosorbent assay for TNF and its soluble receptors. Univariate and multivariate analyses were performed with a forward regression procedure that included all of the parameters that were found to be significant in the univariate analysis. The dose of chemotherapy and the prophylactic treatment with granulocyte colony-stimulating factor were deliberately included in this model.


RESULTS
Sixty-seven patients experienced World Health Organization (WHO) grade 4 neutropenia, and 37 patients experienced febrile neutropenia, which was responsible for WHO grade 2 through 4 infections in 23 patients. In multiparametric 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 duration of grade 4 neutropenia for more than 5 days was associated with the lack of hematopoietic growth factor administration (OR, 6.76; P =.004) and high levels of soluble p75-R-TNF (OR, 5.84; P =.0023). The occurrence of febrile neutropenia was associated with high doses of cyclophosphamide (OR, 4.7; P =.007), altered performance status (OR, 18.8; P <.0001) and high levels of soluble p75-R-TNF (OR, 3.49; P =.029).


CONCLUSIONS
This study indicates that in addition to the dose of chemotherapy and the administration of hematopoietic growth factors, poor performance status and high p75-R-TNF levels can predict the occurrence of chemotherapy-induced myelosuppression in lymphoma patients. This model may help in selecting patients for prophylactic growth factor administration.
Voog
E
E
Service d'Hématologie and Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Bienvenu
J
J
Warzocha
K
K
Moullet
I
I
Dumontet
C
C
Thieblemont
C
C
Monneret
G
G
Gutowski
M C
MC
Coiffier
B
B
Salles
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008024:Ligands; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000175:diagnosis; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D003520:Cyclophosphamide