Prognostic impact of minimal disseminated disease and immune response to NPM-ALK in Japanese children with ALK-positive anaplastic large cell lymphoma

The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic large cell lymphoma (ALCL) was reported by an Italian/German group. Here, we examine their prognostic value in Japanese children with ALK-positive ALCL. We evaluated nucleophosmin (NPM)-ALK transcripts in 60 patients at diagnosis by RT-PCR and real-time PCR (qPCR). The antibody titer was assessed in 35 patients. Fifty-two percent were MDD positive by RT-PCR and 37% had more than 10 copies of NPM-ALK per 104 copies of ABL (10NCNs) by qPCR. Fifty-one percent of 35 patients had high antibody titer (> 1/750). Progression-free survival (PFS) of the patients with > 10 NCNs or low antibody titers was significantly poorer than that of patients with ≤ 10 NCNs or high antibody titers (> 1/750) (P = 0.016, 0.029), respectively, although we observed no difference in PFS associated with positive MDD on RT-PCR. On stratification using a combination of MDD and antibody titer, PFS for patients with > 10 NCNs and low antibody titer was extremely low (30.0%). Combined evaluation of MDD and anti-ALK antibody titer at diagnosis may thus be valuable for stratification of treatment for childhood ALCL.