Reduced-intensity allogeneic stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation

Background: To date, no effective curative option is available for children with neuroblastoma (NB) who failed tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). The present study evaluated the feasibility and efficacy of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) in six children with NB who failed tandem HDCT/autoSCT. Procedure: A cyclophosphamide/fludarabine regimen was used as a conditioning for HLA-matched SCT, and ATG was added for haploidentical SCT. Peripheral blood stem cells from four HLA-matched donors and two haploidentical donors were transplanted. Immune suppression was rapidly tapered if graft-versus-host disease (GVHD) was absent. Results: Regimen-related short-term toxicity was manageable, and complete donor chimerism was achieved in the early period after transplant. Grade I/II acute GVHD developed or was induced in all patients. Tumor response, attributed to a graft-versus-tumor (GVT) effect, was observed in two of six patients after induction of acute GVHD. The other four patients with significant tumor burden prior to transplant had tumor progression despite presence of GVHD. However, it was difficult to effectively reduce the tumor burden prior to transplant through the use of conventional treatment modalities. Conclusion: Although regimen-related short-term toxicity was manageable in intensively pretreated patients with NB, GVT effect was not sufficiently strong to control tumor progression in patients who had a significant tumor burden at transplant. Therefore, new treatment modalities to effectively reduce tumor burden prior to transplant in concert with post-transplant adjuvant treatment to enhance the GVT effect are needed to improve the outcome after RI alloSCT.