Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

SIMPLE SUMMARY: Germ cell tumors (GCTs) are malignancies derived from germ cells that originate in gonads or extragonadal localizations. They are considered highly curable in both children and adults even if distant metastases are present, but therapy-resistant or relapsing patients have a worse prognosis. The aim of our retrospective study was to analyze the outcome of 18 children with GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy and autologous stem cell transplantation. To date, this is one of the largest reported pediatric cohorts of GCT patients treated with megatherapy. We observed high survival rates—a five-year overall survival of 76%, and event-free survival of 70.8% without therapy-associated mortality. We concluded that this megatherapy protocol is feasible in heavily pretreated children, but the issue of precise indications for high dose chemotherapy (HDCT) is evident and must be answered in a well-designed controlled study to avoid unnecessary overtreatment. ABSTRACT: Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m(2), etoposide 1800 mg/m(2), and melphalan 140 mg/m(2)) and MEC2 (carboplatin 800 mg/m(2), etoposide 800 mg/m(2), and melphalan 140 mg/m(2)) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.