Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens for malignant brain tumors in children and young adults.

Abstract

The number of studies examining the use of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) to treat high-risk or recurrent brain tumors is increasing. However, studies addressing the toxicity associated with tandem HDCT/auto-SCT, particularly during the second HDCT/auto-SCT, are very limited. For this reason, we retrospectively evaluated the toxicity of tandem HDCT/auto-SCT with carboplatin-thiotepa-etoposide (CTE) and cyclophosphamide-melphalan (CM) regimens when used to treat high-risk or recurrent brain tumors. A total of 109 patients who received a first HDCT/auto-SCT and 100 who proceeded to a second HDCT/auto-SCT between May 2005 and December 2013 were included. Hematologic recovery was rapid during both the first and second HDCT/auto-SCT. In the first HDCT/auto-SCT, mucositis-related gastrointestinal toxicity was frequent, and two (1.8%) patients died from toxicity [one hepatic veno-occlusive disease (VOD) and one sepsis]. In the second HDCT/auto-SCT, mucositis-related toxicity was milder than in the first round. However, hepatic VOD frequency was high (20.0%), and six (6.0%) patients died from toxicity (four hepatic VODs, one asphyxia, and one sepsis). Multivariate analysis indicated that age younger than 8years was the only significant predictor for hepatic VOD. All six patients who died from toxicity during the second HDCT/auto-SCT were younger than 9years of age. This study demonstrates that tandem HDCT/auto-SCT using CTE/CM regimens was generally feasible. However, dose reduction during the second HDCT/auto-SCT in young children might be needed to decrease the death rate from toxicity.