High-Dose Chemotherapy with Busulfex and Melphalan As Conditioning Regimen Followed By Autologous STEM CELL Rescue for Pediatric Patients with High-Risk Neuroblastoma

Introduction: High-dose chemotherapy with stem cell rescue (auto-transplant) became a well established consolidation procedure for high-risk neuroblastoma patients. We summarize our cumulative experience using busulfex and melphalan rather than carboplatin/etoposide/melphalan as preparative regimen for transplanting these pediatric patients.

Patients & Methods: Six pediatric patients aged 4-10 year old (median 5.75 year old), 3 males and 3 females underwent auto-transplant. All received busulfex 0.95-1.1mg/kg/dose, 16 doses on days -7 to -3 and melphalan 140mg/m², one dose on day -1. Busulfex levels were measured and appeared to range between 981-1222mM per minute (median: 1136mM per minute), with no correction needed (normal level range of 850-1400mM per minute). Cell reconstitution included total nuclear cell (TNC) dose of 5.01-23.7x10⁸/kg (median 15.2x10⁸/kg) cells, and CD34+ cell content of 4.15-9.58x10⁶/kg (median 6.26x10⁶/kg) cells.

Results: Conditioning was well tolerated. No patient developed veno-occlusive-disease (VOD) of the liver. Trilineage engraftment was documented in all patients and none exhibited graft failure. Time to recovery of absolute neutrophil count >0.5x10⁹/L was 9 - 11 (median 9) days. The time to platelet recovery >or=20 and >or=50x10⁹/L ranged from 11 to 12 (median 12) days, and from 12 to 32 (median 22) days, respectively. One patient did not achieve platelets count above 20x10⁹/L and another one did not achieve platelets count above 50x10⁹/L, before their discharge. Hospitalization period ranged between 23-29 days (median: 26 days). Moderate to severe mucositis was the major adverse event post transplant, causing all patients to be supported by total parental nutrition (TPN) for 7-12 days (median: 11 days).  Three patients suffered from culture-negative febrile neutropenia and received antibiotics until neutrophil engraftment. Transplant-related mortality did not occur in any of the patients.

Conclusions: Busulfex and melphalan -based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and may be considered for pediatric patients with high-risk neuroblastoma in need for auto-transplant. Larger cohort of patients is needed to further confirm our results.