Abstract
Peripheral blood cytokines are known prognostic parameters in diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy, but their role after the introduction of rituximab is unknown. Seven polymorphisms in the promoter regions of IL-6, IL-10 and NF-κB1 genes were assessed in 167 patients with DLBCL and 99 controls and correlated with interleukin-6 (IL-6) and IL-10 plasma levels. Outcome was analyzed in 137 patients treated with rituximab-based chemotherapy. The NF-κB1 - 94ATTG deletion was associated with increased IL-6 and IL-10 in DLBCL. High IL-6 concentration correlated with unfavorable prognostic factors included in the international prognostic index (IPI) and predicted for inferior progression-free (p = 0.007) and overall survival (p = 0.02). IL-6 levels remained a significant outcome predictor also including IPI as a covariate (p = 0.006 for progression-free survival). Our data suggest that the NF-κB1 genetic background influences IL-6 production in DLBCL, and that high IL-6 concentration is an independent prognostic factor also in the "rituximab era."
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal, Murine-Derived / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Carboplatin / administration & dosage
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Cyclophosphamide / administration & dosage
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Cytarabine / administration & dosage
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Doxorubicin / administration & dosage
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Female
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Gene Expression Regulation, Neoplastic / genetics
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Genotype
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Humans
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Interleukin-10 / blood*
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Interleukin-10 / genetics
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Interleukin-6 / blood*
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Interleukin-6 / genetics
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Kaplan-Meier Estimate
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Lymphoma, Large B-Cell, Diffuse / drug therapy
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Lymphoma, Large B-Cell, Diffuse / genetics*
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Lymphoma, Large B-Cell, Diffuse / mortality
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Male
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Methylprednisolone / administration & dosage
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Middle Aged
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Mitoxantrone / administration & dosage
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NF-kappa B p50 Subunit / genetics*
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NF-kappa B p50 Subunit / physiology
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / physiology
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Phenotype
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Polymorphism, Single Nucleotide*
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Prednisone / administration & dosage
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Prognosis
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Promoter Regions, Genetic / genetics
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Rituximab
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Sequence Deletion
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Treatment Outcome
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Vincristine / administration & dosage
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Young Adult
Substances
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Antibodies, Monoclonal, Murine-Derived
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IL10 protein, human
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IL6 protein, human
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Interleukin-6
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NF-kappa B p50 Subunit
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NFKB1 protein, human
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Neoplasm Proteins
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Cytarabine
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Interleukin-10
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Rituximab
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Carboplatin
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Mitoxantrone
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Prednisone
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Methylprednisolone
Supplementary concepts
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CHOP protocol
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MiCMA protocol