Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-2, and Haploidentical Natural Killer Cells

Biol Blood Marrow Transplant. 2017 Nov;23(11):1910-1917. doi: 10.1016/j.bbmt.2017.07.011. Epub 2017 Jul 18.

Abstract

The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen that combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplantation (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs). Here we report on 30 patients who have undergone AHCT with this experimental immunotherapy regimen, 21 of whom received haploidentical NKs. The median time to neutrophil engraftment was 13 days (range, 10 to 28 days) and to platelet engraftment of at least 20 × 103/mm3 was 36.5 days (range, 0 to 102 days); no clinical difference was seen in those who did or did not receive NKs. Eight patients developed veno-occlusive disease, with 3 having multiorgan dysfunction. Toxicities were similar for patients who did or did not receive NKs. We conclude that this consolidation regimen is feasible and has an acceptable acute toxicity profile.

Keywords: Autologous transplantation; GD2 monoclonal antibody; Immunotherapy; Natural killer cells; Neuroblastoma.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / therapeutic use*
  • Child, Preschool
  • Consolidation Chemotherapy / methods*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Natural / metabolism*
  • Male
  • Melphalan / therapeutic use*
  • Neuroblastoma / drug therapy*
  • Prospective Studies
  • Transplantation, Autologous / methods*

Substances

  • Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Busulfan
  • Melphalan