Impact of Fc gamma-receptor polymorphisms on the response to rituximab treatment in children and adolescents with mature B cell lymphoma/leukemia
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27376362
DOI
10.1007/s00277-016-2731-x
PII: 10.1007/s00277-016-2731-x
Knihovny.cz E-zdroje
- Klíčová slova
- Fc gamma-receptor, Lymphoma, Oncology, Response, Rituximab,
- MeSH
- B-buněčný lymfom krev farmakoterapie genetika MeSH
- dítě MeSH
- frekvence genu MeSH
- genotyp MeSH
- indukce remise MeSH
- jednonukleotidový polymorfismus * MeSH
- L-laktátdehydrogenasa krev metabolismus MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mladiství MeSH
- multivariační analýza MeSH
- prognóza MeSH
- protinádorové látky terapeutické užití MeSH
- receptory IgG genetika MeSH
- rituximab terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- FCGR2A protein, human MeSH Prohlížeč
- FCGR3A protein, human MeSH Prohlížeč
- L-laktátdehydrogenasa MeSH
- protinádorové látky MeSH
- receptory 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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