Secondary Dysgammaglobulinemia in Children with Hematological Malignancies Treated with Targeted Therapies

Abstract

Targeted therapies have emerged as innovative treatments for patients whose disease does not respond to conventional chemotherapy, and their use has widely expanded in the field of pediatric hematologic malignancies in the last decade. While they carry the promise of improved disease control and survival and are currently investigated in first-line treatment protocols for patients with poor prognostic markers, they are associated with a considerable incidence of specific toxicities, including cytokine-release syndrome, neurotoxicity, hepatotoxicity, nephrotoxicity, cardiotoxicity, endocrine adverse events, and infectious complications. Iatrogenic or secondary dysgammaglobulinemia is a main consequence of targeted therapies using monoclonal antibodies and other antibody-derived treatments that target specific antigens on lymphoid cells (blinatumomab, inotuzumab ozogamicin, rituximab), chimeric antigen receptor T cells, tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) and, to a lesser extent, checkpoint inhibitors (pembrolizumab, nivolumab). This review discusses the diagnosis and incidence of secondary or iatrogenic dysgammaglobulinemia in children treated with targeted therapies for leukemias and lymphomas, and options for monitoring and treatment.

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

“…IgG levels >800 mg/dL are recommended especially for children <10 years of age and when there are relevant risk factors (baseline pulmonary pathology, history of total body irradiation, or added immunosuppression by chronic graft-versus-host disease). Replacement therapy should last as long as B-cell aplasia and HGG persist [ 154 , 175 ].…”