Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma

Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012. doi: 10.1016/j.bbmt.2017.12.805. Epub 2018 Jan 4.


Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 106/kg T/B cell-depleted CD34+ stem cells with 68 × 103/kg residual T cells and 107 × 106/kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system.

Keywords: Allogeneic stem cell transplantation; Graft-versus-host disease; Graft-versus-tumor effect; Haploidentical; Neuroblastoma; Transplantation-related mortality.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD34 / blood
  • Antineoplastic Combined Chemotherapy Protocols
  • Child
  • Child, Preschool
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Lymphocyte Depletion
  • Neuroblastoma / mortality
  • Neuroblastoma / therapy*
  • Prognosis
  • Salvage Therapy / methods*
  • Salvage Therapy / mortality
  • Survival Analysis
  • Transplantation Conditioning
  • Transplantation, Haploidentical / methods*
  • Transplantation, Haploidentical / mortality
  • Treatment Outcome


  • Antigens, CD34