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

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/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) 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.

Favorable outcome of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with nonmetastatic osteosarcoma and low-degree necrosis

“…We used a melphalan/etoposide/carboplatin regimen, which was different from the studies that conducted HDC in OSA. This regimen has already been used for a variety of childhood cancers and is familiar to pediatricians ( 20 – 22 ). All of these medications are known to be effective in OSA, and we have confirmed through a previously reported pilot study that the melphalan/etoposide/carboplatin regimen showed good treatment results, especially in localized OSA patients with low-degree necrosis ( 14 ).…”

Pediatric Extracranial Germ Cell Tumors: Review of Clinics and Perspectives in Application of Autologous Stem Cell Transplantation

“…One recent cohort study included 18 children with R/R GCTs in Poland who were treated with melphalan-etoposide-carboplatin HDCT; they showed 5-year OS and 5-year EFS of 76% and 70.8%, respectively. Patients younger than 4 years of age who received HDCT combined with ASCT had an even higher survival rate [ 88 ]. Another recent AIEOP report considered 16 out of 21 children with R/R GCTs who received HDCT; 13 out of 16 (81%) patients were alive without treatment-related death [ 72 ].…”

“…The 5-year OS and 5-year EFS was 76% and 70.8%. For the children younger than 4 years old, the OS and EFS were even higher [ 88 ].…”