Anaplastic large cell lymphoma in children and adolescents

Abstract

Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) accounts for >95% of ALCL cases in children and adolescents. The first description of ALCL as a CD30-positive lymphoma in 1985 was followed by the detection of chromosomal translocations involving the ALK gene at chromosome 2p23. The pathogenesis of ALK-positive ALCL is based on signalling from the constitutive active ALK kinase. The clinical characteristics, therapy regimens and outcome data were reported in the 1990s and 2000s. Different chemotherapy regimens led to astonishingly similar long-term event-free survival rates of 70%, independent of the drugs, doses and duration of therapy. Additionally, patients with relapsed ALCL are treated successfully with very different re-induction and consolidation approaches leading to an overall survival approaching 95%. In the 2010s, minimal disseminated and residual disease, histological subtype and antibody titres against ALK were reported as significant independent prognostic factors. Over the last 15 years, targeted therapies (brentuximab vedotin, ALK inhibitors) have demonstrated high efficacy with low toxicity. The future of ALK-positive ALCL is to define the role of targeted therapies by developing a 'chemotherapy-free' approach for patients with standard-risk ALCL and an integrated approach to cure patients with high-risk ALCL.

Keywords: anaplastic large‐cell lymphoma; anaplastic lymphoma kinase; children; diagnosis; therapy.

FIGURE 1

Clinical presentations of children with anaplastic lymphoma kinase‐positive anaplastic large‐cell lymphoma. (A) Skin involvement, (B) lung involvement, (C) bone and soft tissue, (D) subcutaneous soft tissue lesion.

FIGURE 2

Signalling from the constitutively activated ALK in NPM‐ALK‐positive ALCL with possible therapeutic targets. ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; NPM, nucleophosmin.