title: Impact of Fc gamma-receptor polymorphisms on the response to rituximab treatment in children and adolescents with mature B cell lymphoma/leukemia.
abstract: 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.
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, University Children's Hospital Muenster, Domagkstrasse 24, D-48149, Muenster, Germany. birgit.burkhardt@ukmuenster.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Deniz
authors.initials: D
authors.lastname: Yavuz
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, University Children's Hospital Muenster, Domagkstrasse 24, D-48149, Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Schieferstein
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University, University Hospital Motol, Prague, Czech Republic.
authors.forename: Edita
authors.initials: E
authors.lastname: Kabickova
authors.affiliation: Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Vienna, Austria.
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lisfeld
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, University Children's Hospital Muenster, Domagkstrasse 24, D-48149, Muenster, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Makarova
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, University Children's Hospital Muenster, Domagkstrasse 24, D-48149, Muenster, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Worch
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, University Children's Hospital Muenster, Domagkstrasse 24, D-48149, Muenster, Germany.
authors.forename: Bettina R
authors.initials: BR
authors.lastname: Bonn
authors.affiliation: Pediatric Hematology and Oncology, NHL-BFM Study Center, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Damm-Welk
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab; D007770:L-Lactate Dehydrogenase
keywords: Fc gamma-receptor; Lymphoma; Oncology; Response; Rituximab