1 INTRODUCTION
Advanced neuroblastoma is an aggressive childhood cancer with a poor prognosis. Multidisciplinary treatment, including multiagent chemotherapy, surgery, radiotherapy, hematopoietic stem cell transplantation, and immunotherapy, aimed at minimizing residual disease has increased the long-term survival rate of patients with high-risk neuroblastoma to 60%. Among the variety of treatment modalities, multiagent chemotherapy consisting of vinca alkaloid, anthracyclines, alkylators, and platinum is still the mainstay1. Accurate control of adverse events during the initial induction chemotherapy is necessary but difficult because the condition of the patients is frequently unstable due to the huge tumor burden both in the abdomen and metastatic sites.
Tumor lysis syndrome (TLS) is a well-known metabolic adverse event resulting from the contents of large numbers of lysed cancer cells being released into the blood stream. Although it occurs during induction chemotherapy for highly chemosensitive malignancies, such as acute leukemia and malignant lymphoma, it is also sometimes observed in advanced neuroblastomas. The immune response provoked by TLS is particularly interesting for its potential role in acute respiratory events (ARE) that are encountered albeit rarely during induction chemotherapy in some patients with advanced neuroblastoma. The incidence of acute respiratory distress syndrome (ARDS), which is considered to be a severe form of ARE occurring during induction chemotherapy for neuroblastoma, is reportedly one in eighty-six (1.2%)3 to one in forty-six (2.2%)2 based on previous case series.
We herein hypothesized that ARE have the same etiology as TLS, and that their risk can be estimated using biologic parameters related to TLS. The present, retrospective, cohort study conducted at two, high-volume centers in Japan, aimed to test these hypotheses.