We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Impact of Fc gamma-receptor polymorphisms on the response to rituximab treatment in children and adolescents with mature B cell lymphoma/leukemia.
- Authors
Burkhardt, Birgit; Yavuz, Deniz; Zimmermann, Martin; Schieferstein, Jutta; Kabickova, Edita; Attarbaschi, Andishe; Lisfeld, Jasmin; Reiter, Alfred; Makarova, Olga; Worch, Jennifer; Bonn, Bettina; Damm-Welk, Christine; Bonn, Bettina R
- 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.
- Subjects
B cell lymphoma; LYMPHOMAS; LYMPHOMAS in children; TUMORS in adolescence; FC receptors; RITUXIMAB; THERAPEUTICS; GENETICS; TUMOR treatment; ANTINEOPLASTIC agents; CANCER relapse; CELL receptors; GENES; GENETIC polymorphisms; LACTATE dehydrogenase; MULTIVARIATE analysis; PROGNOSIS; TREATMENT effectiveness; DISEASE remission; GENOTYPES
- Publication
Annals of Hematology, 2016, Vol 95, Issue 9, p1503
- ISSN
0939-5555
- Publication type
journal article
- DOI
10.1007/s00277-016-2731-x