CURRENT APPROACHES TO DIAGNOSIS AND TREATMENT OF ANAPLASTIC LARGE CELL LYMPHOMA IN CHILDREN
Introduction. Current chemotherapy regimen allow to cure for about 70% of children with anaplastic large cell lymphoma (ALCL), however, recurrence rate is high, up to 30%. Therefore search for the adverse prognostic factors remains actual and one of the main relapse predictors appears to be minimal disseminated (MDD) and minimal residual disease (MRD). Purpose. We aimed to evaluate performance and clinical significance of qualitative and quantitative detection of the NPM/ALK fusion gene for the MDD and MRD assessment in childhood ALCL. Patients and methods. We retrospectively reviewed diagnostic data and treatment results of 45 ALCL patients from 1 to 24 years old (median age, 13.7) treated in our hospital in 1992-2015. Eighteen patients were treated according to modified NHL-BFM 90, and 27 - according to ALCL 99 protocol. Treatment of 7 patients was changed due to the MRD positivity. ALK-positive cases accounted for 97% and NPM/ALK-positive for 83% of all ALCL. MDD assessment was performed in 24 patients, MRD in 11. NPM/ALK expression was performed by nested and/or real time PCR either in bone marrow (BM) or peripheral blood (PB) at diagnosis and before each chemotherapy course. Results. With a median follow-up of 5 years overall survival for all 45 patients was 75%. MDD was revealed in 67% of patients (in 58% of BM, and in 56% of PB samples). Concordant results of NPM/ALK expression in BM and PB were obtained in 89% of cases. NPM/ALK levels in PB were higher or comparable to those in BM either at diagnosis or during the treatment. MRD was positive after prephase in 88%, before the 2 <sup>nd</sup> course in 43%, before the 3d in 38%, before the 4 <sup>th</sup> in 33% of cases. The treatment of 7 MRD-positive patients was intensified, and allogeneic BM transplantation was performed in 2 of them. All 7 patients are in the first complete remission with a follow-up from 6 months to 7 years. Conclusions. NPM/ALK detection in PB by qualitative PCR it seems to be appropriate for MDD assessment while quantitative PCR is preferable for MRD control. Intensified treatment in MRD-positive patients can prevent relapse and improve outcome.