A PILOT TRIAL OF TANDEM AUTOLOGOUS PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION FOLLOWING HIGH-DOSE THIOTEPA AND CARBOPLATIN IN CHILDREN WITH POOR-RISK CENTRAL NERVOUS SYSTEM TUMORS

Abstract

This is a pilot study performed to determine the maximum tolerated number of courses of high-dose thiotepa and carboplatin with autologous peripheral blood progenitor cell (PBPC) transplantation in poor-risk pediatric central nervous system (CNS) tumor patients. Twelve patients were enrolled and a total of 24 PBPC transplants were performed. The median age was 7.7 years. All patients had CNS tumors: 4 relapsed CNS PNET, 2 high-risk PNET in first remission, 2 relapsed/progressive brainstem tumor, 2 relapsed/progressive anaplastic astrocytoma, 1 relapsed GBM, and 1 recurrent ependymoma. The regimen consisted of thiotepa 250 mg/m²/day × 3 days and carboplatin 400 mg/m²/day × 3 days. No toxic deaths occurred. All patients were hospitalized for a median duration of 17 days. The median number of CD34 cells infused was 5.4 × 10⁶/kg (2.1–29.7 × 10⁶/kg) per course. Median time to ANC >0.5 × 10⁹/L was 9 days, and platelets >20 × 10⁹/L was 13.5 days. Four patients came off protocol after only one course of PBPC (2 had tumor progression, 2 parental choice); 4 patients underwent two, and 4 patients three courses of PBPC. Major nonhematologic complications were mucositis that necessitated infusion of narcotics (11/24 courses), fever of unknown origin (12/24), documented infection (9/24), and hemorrhagic cystitis (3/24). TPN was administered during 22 of 24 courses with a median duration of 15 days. It is feasible to administer 2–3 courses of tandem high-dose thiotepa and carboplatin with PBPC transplant with prompt engraftment and manageable toxicities in pediatric CNS tumor patients.

Keywords:

• carboplatin
• pediatric solid tumors
• tandem peripheral blood progenitor cell transplant
• thiotepa