Tandem high-dose chemotherapy with thiotepa and busulfan-melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients.

Tandem high-dose chemotherapy with thiotepa and busulfan-melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients.

Pasqualini, C 2016, BMT (Link to abstract)



This is a European study (2004-2011) of very high risk (VHR) NBL patients (HR patients who had metastatic disease at end of induction) had therapy intensified to received two tandem autologous HSCTs with thiotepa, then busulfan-melphalan, with a two-month interval between.  Defibrotide VOD prophylaxis was standard practice.   26 patients received tandem transplants and only 5 were MYCN amplified.  Six patients (25%) developed VOD, one died, toxicity was otherwise typical of autologous HSCT, but higher rate and severity with the second transplant.  6/24 patients achieved CR, 7 PR, 10 stable disease.  OS at 3 years was 69%, EFS was 37.3%.


[*In comparison, following ANBL0532 HR NB study, COG recommends the use of tandem transplant consolidation (with thiotepa/cyclophosphamide then carbo, etop, melphalan (CEM)) for patients greater than 18 months of age with INSS stage 4 neuroblastoma or those of any age with INSS stage 2B, 3 or 4 and MYCN amplification high-risk neuroblastoma based upon the significantly improved 3- year EFS following tandem transplant.]


* The outcome in this cohort was promising and it appeared to be safe to perform tandem transplant with VHR NBL.  An upcoming SIOPEN study will compare tandem HDC with thiotepa and BuMEL (this protocol) with mIBG/BuMel autoHSCT.