Impact of Fc gamma-receptor polymorphisms on the response to rituximab treatment in children and adolescents with mature B cell lymphoma/leukemia
Language English Country Germany Media print-electronic
Document type Journal Article
PubMed
27376362
DOI
10.1007/s00277-016-2731-x
PII: 10.1007/s00277-016-2731-x
Knihovny.cz E-resources
- Keywords
- Fc gamma-receptor, Lymphoma, Oncology, Response, Rituximab,
- MeSH
- Lymphoma, B-Cell blood drug therapy genetics MeSH
- Child MeSH
- Gene Frequency MeSH
- Genotype MeSH
- Remission Induction MeSH
- Polymorphism, Single Nucleotide * MeSH
- L-Lactate Dehydrogenase blood metabolism MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Adolescent MeSH
- Multivariate Analysis MeSH
- Prognosis MeSH
- Antineoplastic Agents therapeutic use MeSH
- Receptors, IgG genetics MeSH
- Rituximab therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- FCGR2A protein, human MeSH Browser
- FCGR3A protein, human MeSH Browser
- L-Lactate Dehydrogenase MeSH
- Antineoplastic Agents MeSH
- Receptors, IgG MeSH
- Rituximab MeSH
Recent studies in adult lymphoma patients have indicated a correlation between polymorphisms of Fc gamma-receptors (FcγRs, encoded by the respective FCGR genes) and the response to rituximab treatment. In vitro, cells expressing FcγRIIIa-158V mediate antibody-dependent cellular cytotoxicity (ADCC) more efficiently than cells expressing FcγRIIIa-158F. The impact of the FCGR2A-131HR polymorphism is unclear. In this study, the FCGR polymorphisms FCGR3A-158VF and FCGR2A-131HR were analyzed in pediatric patients with mature aggressive B cell non-Hodgkin lymphoma/leukemia (B-NHL). Pediatric patients received a single dose of rituximab monotherapy. Response was evaluated on day 5 followed by standard chemotherapy for B-NHL. Among 105 evaluable patients, a response to rituximab was observed in 21 % of those homozygous for FcγRIIa-131RR (5/24) compared to 48 % of patients who were HH and HR FcγRIIa-131 allele carriers (18/34 and 21/47, respectively; p = 0.044). Among patients with the FCGR3A-158 polymorphism, those homozygous for the FF genotype had a significantly favorable rituximab response rate of 59 % (22/37) compared to 32 % in patients who were FcγRIIIa-158VV and FcγRIIIa-VF allele carriers (2/9 and 20/59, respectively; p = 0.022). A stringent phase II response evaluation of children and adolescents with B-NHL after one dose of rituximab monotherapy showed a significant association between the rituximab response rate and FCGR polymorphisms. These findings support the hypothesis that FCGR polymorphisms represent patient-specific parameters that influence the response to rituximab.
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