Strategy for Pediatric Patients with Relapsed or Refractory Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: A Review

Simple Summary Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Approximately 30% of patients treated with conventional chemotherapy experience a relapse or refractory disease and have a poor prognosis. Several risk factors associated with poor prognosis have been identified in pediatric ALK-positive ALCL, such as the morphological pattern of the small cell variant or lymphohistiocytic variant, leukemic presentation, the presence of minimal disseminated disease, or involvement of the central nervous system. Relapsed or refractory ALK-positive ALCL requires salvage therapy. Recently, targeted therapies such as ALK inhibitors and brentuximab vedotin have demonstrated dramatic responses in chemoresistant ALK-positive ALCL. Hematopoietic stem cell transplantation has also been reported to be an effective therapy. This article reviews pediatric ALK-positive ALCL, focusing on the risk factors associated with poor prognosis and treatment strategies for relapsed or refractory disease.Abstract Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Although conventional chemotherapy is effective in most patients, approximately 30% experience a relapse or refractory disease and have a poor prognosis. Several risk factors associated with poor prognosis have been identified in pediatric ALK-positive ALCL. These include morphological patterns with the small cell variant or lymphohistiocytic variant, leukemic presentation, the presence of minimal disseminated disease, or involvement of the central nervous system. Relapsed or refractory ALK-positive ALCL is often resistant to conventional chemotherapy; therefore, salvage therapy is required. In recent years, targeted therapies such as ALK inhibitors and brentuximab vedotin (BV) have been developed. ALK inhibitors block the continuous activation of ALK kinase, a driver mutation that leads to cell proliferation in ALK-positive ALCL. Additionally, BV is an antibody-drug conjugate that targets CD30-positive cells. Both ALK inhibitors and BV have displayed dramatic effects in chemoresistant ALK-positive ALCL. Weekly vinblastine treatment and hematopoietic stem cell transplantation have also been reported to be effective therapies. This article reviews pediatric ALK-positive ALCL, focusing on risk factors and treatment strategies for pediatric patients with relapsed or refractory ALK-positive ALCL.