Thiotepa and cyclophosphamide with stem cell rescue for consolidation therapy for children with high-risk neuroblastoma: A phase I/II study of the pediatric blood and marrow transplant consortium

Purpose: We report the results of a phase I/II stem cell rescue trial for patients with high risk neuroblastoma. Patients and Methods: Fifty-one patients with a median age of 2.3 years (range 1 to 20) who were in their first complete remission (CR) (n = 8), very good partial remission (VGPR) (n = 23), partial remission (PR) (n = 5), or subsequent CR/PR (n = 7) after receiving a platinum-based induction regimen were consolidated with high dose chemotherapy and stem cell rescue. They received an ablative regimen of thiotepa (300 mg/m²/day for 3 days) and cyclophosphamide (1500 mg/m²/day for 4 days) followed by either purged marrow (n = 16), unpurged bone marrow (BM) (n = 23), or peripheral blood stem cell (PBSC) rescue (n = 13). The median nucleated cell doses administered were 2.7x10⁸/kg for unpurged marrow (range 1.1 to 13), 1.7x10⁸/kg for purged marrow (range 0.8 to 6.4), and 2.1x10⁸/kg for the PBSC (range 1.1 to 13). Results: Engraftment was achieved for all patients. The time to achieve an absolute neutrophil count (ANC) >500x10⁹/l was 19 days for patients who received purged BM (range 13 to 18), 17.5 days for patients who received unpurged PBSC (range 9 to 25). An unsustained platelet count >20x10⁹/l was attained in 33.5 days by patients who received purged BM (range 13 to 100), 35 days for patients who received unpurged BM (range 14 to 128), and 20 days for patients who received PBSC (range 11 to 64). There was one infectious death in the unpurged marrow group caused by aspergillosis pneumonia, but none in the other two groups. Progressie disease (PD) developed in 21 patients at a median of 271 days (range 31 to 1230). The remainnig 29 patients are progression-free at a median follow-up of 1190 days (range 530 to 2383). Conclusion: We conclude that this regimen is well tolerated, and that progression-free survival (PFS) with this chemotherapy-only regimen compares favorably with regimens containing total body irradition (TBI).