Phase I study of tandem high-dose chemotherapy with autologous peripheral blood stem cell rescue for children with recurrent brain tumors: A pediatric blood and marrow transplant consortium study

Background High‐dose chemotherapy with autologous stem cell rescue (HDC/SCR) has produced responses and prolonged survival for some children with recurrent brain tumors, but is associated with considerable morbidity and mortality. A Phase I trial of two cycles of HDC/SCR for recurrent brain tumors in children was performed to determine the maximum tolerated doses for a novel regimen. Procedures Two cycles of HDC/SCR were given. Cycle 1 included thiotepa and carmustine given on days −5, −4, and −3. Four to six weeks later, patients received cycle 2 which included thiotepa and carboplatin given on days −5, −4, and −3. Autologous peripheral blood stem cells (PBSC) were infused on day 0 of each cycle. Results Thirty‐two patients were treated and 25 patients received both cycles of HDC/SCR. Common toxicities included mucositis, emesis, diarrhea, anorexia, and pancytopenia. Eight of 32 (25%) assessable children died from regimen‐related toxicity. Pulmonary failure occurred in seven patients. Seven patients had grade 3–4 neurotoxicity. The 3‐year event‐free survival (EFS) was 25%. Conclusions We determined the maximum tolerated regimen to be thiotepa 600 mg/m2 and carmustine 300 mg/m2 followed by thiotepa 600 mg/m2 and carboplatin 1,200 mg/m2. Pulmonary toxicity was considerable. The toxic death rate was similar to other trials of HDC/SCR for children with recurrent brain tumors performed during the same time period. The regimen resulted in prolonged time to progression for a significant number of patients and long‐term survival for some patients with recurrent medulloblastoma and rhabdoid tumor. Pediatr Blood Cancer 2011; 57: 506–513. © 2010 Wiley‐Liss, Inc.