Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL

naplastic large-cell lymphoma (ALCL) makes up approximately 15% of pediatric non-Hodgkin's lymphoma (NHL) and the vast majority of them is associated with the t(2;5) translocation that results in the expression of a hybrid oncogenic tyrosine kinase. It consists of the amino terminus of the nuclear protein nucleophosmin (NPM) fused to the intracytoplasmic region of the anaplastic lymphoma kinase (ALK) that impacts many cellular responses including proliferation, growth and apoptosis.1 In addition to its direct effects of ALK on signal transduction pathways, ALK overexpression may also induce a host immune reaction, giving rise to autologous anti-ALK antibodies in patients with ALK-positive ALCL. Circulating antibodies against NPM-ALK were originally reported in 11 ALK-positive ALCL patients using an immunocytochemical approach.2 In that study, no conclusions concerning the clinical significance of anti-NPM-ALK antibodies could be drawn, due to the small number of patients; however, a tendency to higher antibody levels in pretreatment blood samples was observed. Recently, we demonstrated that minimal bone marrow (BM) involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring can identify patients at risk of relapse.3 In addition, Damm-Welk et al.4 showed that patients with more than 10 normalized copy numbers (NCNs) NPM-ALK in BM had a cumulative incidence of relapse (CI-R) of 71plusminus14% compared with CI-R of 18plusminus6% for patients with 10 or fewer NCNs (P<0.001) and that quantitative PCR for NPM-ALK in BM and peripheral blood (PB) is highly concordant. In this study, we assessed the levels of anti-NPM-ALK antibodies at diagnosis and at stop therapy in plasma of children with ALCL treated according to the ALCL-99 protocol5 and evaluated the possible correlation with minimal residual disease (MRD) status during chemotherapy