Homozygous <i><scp>FCGR3A</scp>‐158<scp>V</scp></i> alleles predispose to late onset neutropenia after <scp>CHOP‐R</scp> for diffuse large <scp>B</scp>‐cell lymphoma

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Recent reports suggest genetic polymorphisms influence susceptibility to rituximab‐induced late‐onset neutropenia (<jats:styled-content style="fixed-case">LON</jats:styled-content>), which in turn may be a predictor of good outcome in <jats:styled-content style="fixed-case">B</jats:styled-content>‐cell lymphoma.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>We report the largest study to date assessing <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐<jats:styled-content style="fixed-case">V158F</jats:styled-content></jats:italic> polymorphisms in diffuse large <jats:styled-content style="fixed-case">B</jats:styled-content>‐cell lymphoma (<jats:styled-content style="fixed-case">DLBCL</jats:styled-content>) treated with cyclophosphamide/hydroxydaunorubicin/<jats:styled-content style="fixed-case">O</jats:styled-content>ncovin (vincristine)/prednisone/rituximab (<jats:styled-content style="fixed-case">CHOP</jats:styled-content>‐<jats:styled-content style="fixed-case">R</jats:styled-content>). The influence of <jats:italic><jats:styled-content style="fixed-case">C1qA</jats:styled-content>‐<jats:styled-content style="fixed-case">A276G</jats:styled-content></jats:italic> polymorphisms in <jats:styled-content style="fixed-case">DLBCL</jats:styled-content>, and the impact of both polymorphisms on susceptibility to <jats:styled-content style="fixed-case">LON</jats:styled-content> and outcome were also examined.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>115 <jats:styled-content style="fixed-case">DLBCL</jats:styled-content> patients treated with <jats:styled-content style="fixed-case">CHOP</jats:styled-content>‐R were compared with 105 healthy <jats:styled-content style="fixed-case">W</jats:styled-content>hite people controls with regards to <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐<jats:styled-content style="fixed-case">V158F</jats:styled-content></jats:italic> and <jats:italic><jats:styled-content style="fixed-case">C1qA</jats:styled-content>‐<jats:styled-content style="fixed-case">A276G</jats:styled-content></jats:italic> polymorphisms. <jats:styled-content style="fixed-case">LON</jats:styled-content> incidence and event‐free and overall survival (<jats:styled-content style="fixed-case">EFS</jats:styled-content> and <jats:styled-content style="fixed-case">OS</jats:styled-content>) were analysed for linkage to either polymorphism.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐<jats:styled-content style="fixed-case">V158F</jats:styled-content></jats:italic> but not the <jats:italic><jats:styled-content style="fixed-case">C1qA</jats:styled-content>‐<jats:styled-content style="fixed-case">A276G</jats:styled-content></jats:italic> polymorphism influenced the risk of developing <jats:styled-content style="fixed-case">LON</jats:styled-content>. 50% of <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐158<jats:styled-content style="fixed-case">V</jats:styled-content>/<jats:styled-content style="fixed-case">V</jats:styled-content></jats:italic> patients experienced <jats:styled-content style="fixed-case">LON</jats:styled-content>. In contrast, only 7% <jats:italic><jats:styled-content style="fixed-case">V</jats:styled-content>/<jats:styled-content style="fixed-case">F</jats:styled-content></jats:italic> and 2% <jats:italic><jats:styled-content style="fixed-case">F</jats:styled-content>/<jats:styled-content style="fixed-case">F</jats:styled-content></jats:italic> experienced <jats:styled-content style="fixed-case">LON</jats:styled-content>. The <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐158<jats:styled-content style="fixed-case">V</jats:styled-content>/<jats:styled-content style="fixed-case">V</jats:styled-content></jats:italic> genotype was associated with <jats:styled-content style="fixed-case">LON</jats:styled-content> compared with <jats:italic><jats:styled-content style="fixed-case">V</jats:styled-content>/<jats:styled-content style="fixed-case">F</jats:styled-content></jats:italic> (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.028) and <jats:italic><jats:styled-content style="fixed-case">F</jats:styled-content>/<jats:styled-content style="fixed-case">F</jats:styled-content></jats:italic> genotypes (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.005). Although no patients with either <jats:styled-content style="fixed-case">LON</jats:styled-content> or <jats:italic><jats:styled-content style="fixed-case">FCGR3A</jats:styled-content>‐158<jats:styled-content style="fixed-case">V</jats:styled-content></jats:italic> homozygosity relapsed compared w ...