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

Aimee C. Talleur, Brandon M. Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L. Furman

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)1910-1917
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number11
DOIs
StatePublished - Nov 2017

Bibliographical note

Funding Information:
The authors acknowledge the St. Jude Children's Research Hospital Comprehensive Cancer Center, American Lebanese Syrian Associated Charities, Cookies for Kids' Cancer, and Cure Childhood Cancer Foundation for their support of this work. The authors thank the St. Jude Children's Research Hospital GMP facility for manufacturing the hu14.18K322A antibody and senior scientific editor Keith Laycock, PhD for his critical review of this manuscript.

Funding Information:
Funding sources: This work was supported by the St. Jude Children's Research Hospital Comprehensive Cancer Center Support Grant ( 2 P30 CA021765 ), American Lebanese Syrian Associated Charities , Cookies for Kids' Cancer and Press On Fund .

Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation

Keywords

  • Autologous transplantation
  • GD2 monoclonal antibody
  • Immunotherapy
  • Natural killer cells
  • Neuroblastoma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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