High dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high risk osteosarcoma

Abstract

Introduction: Despite the greatly improved overall survival of high risk osteosarcoma, treatment outcomes remain poor for patients with poor response to neo-adjuvant chemotherapy or metastatic disease, and those who progress during treatment or relapse after completion of conventional therapy. Patients with these risk factors were treated with high dose chemotherapy and autologous stem cell transplantation (HDCT & ASCT) to overcome their poor survival. We herein analyzed the treatment outcome of these patients, and evaluated the feasibility of HDCT & ASCT for high risk osteosarcoma.

Methods: Medical record review was done on children with high risk osteosarcoma who underwent HDCT & ASCT with melphalan, etoposide and carboplatin at Seoul National University Childrens Hospital between March 2006 and March 2013. High risk osteosarcoma was defined as those with tumor necrosis below 90% after neo-adjuvant chemotherapy, metastasis at diagnosis, progression during treatment or relapse after completion of conventional therapy.

Results: HDCT & ASCT was performed in 19 patients at median age of 12.4 years old (range, 6.1 to 19.7 years old), at median 9 months (range, 6 to 51 months) from diagnosis. They underwent HDCT & ASCT for tumor necrosis below 90% after neo-adjuvant chemotherapy only (n=8, Group I), for initial lung metastasis, with or without poor response to neo-adjuvant chemotherapy (n=5, Group II), for progression during treatment, regardless of presence of initial lung metastasis or poor response to neo-adjuvant chemotherapy (n=3, Group III), and for relapse after completion of conventional therapy (n=3, Group IV). Median 6.1 × 10^6/kg CD34 cells were infused, and neutrophils engrafted at median 10 days from infusion. Grade 4 adverse events occurred in 3 patients, and these resolved in 2 patients. Transient veno-occlusive disease occurred in 4 patients. One patient died of transplantation-related mortality. The event-free survival was 67.4% at median 31 months (range, 0 to 91 months) from HDCT & ASCT. Five patients (26%) relapsed

2 patients achieved remission with further chemotherapy, 1 patient is currently on chemotherapy, and 2 patients refused further treatment and died of disease. The overall survival was 78.3% at median 31 months (range, 0 to 91 months) from ASCT.

Conclusions: HDCT & ASCT with melphalan, etoposide and carboplatin may be a promising treatment option for high risk osteosarcoma. Further strategies are needed to overcome relapses after HDCT & ASCT.