CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma

Pediatr Blood Cancer. 2011 Jan;56(1):134-42. doi: 10.1002/pbc.22840.

Abstract

Background: Graft contamination has been blamed for causing relapse in children with high-risk neuroblastoma (HRNB) after autologous hematopoietic stem cell transplantation (HSCT).

Procedure: We report the long-term results of hematopoietic reconstitution, post-transplant complications, and clinical outcome of 44 children with HRNB treated with busulfan/melphalan high-dose chemotherapy followed by transplantation of purged CD34+ immunoselected autologous peripheral HSCT. Minimal residual disease (MRD) of grafts was evaluated by anti-GD2 immunofluorescence or tyrosine hydroxylase reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Contaminating neuroblasts were found in 19/38 grafts (50%) before CD34+ positive selection, and none after (technique sensitivity of one cell in 10(5)). A median of 6.5 × 10(6) CD34+ cells/kg (range 0.8-23.7) were transplanted with only 2% of TRM. Neutrophils and platelet recovery occurred within a median of 12 days (range 9-47) and 44 days (range 12-259), respectively, without any secondary graft failure. Twenty-three percents of patients experienced a sepsis (10/44) and 14% a pyelonephritis (6/44). Recurrence of varicella zoster virus occurred in 21% of patients (9/44). Negative RT-PCR MRD within the leukapheresis product and cis-retinoic acid therapy were significantly and independently associated to a better survival (P < 0.05). Overall and event-free survivals at 5 years post-transplant were at 59.3% and 48.3% respectively.

Conclusions: Besides high rates of manageable infections due to late immune recovery, transplantation with CD34+ immunoselected grafts in HRNB children was feasible and did not affect long-term hematopoiesis.

Publication types

  • Clinical Trial

MeSH terms

  • Antigens, CD34*
  • Busulfan / therapeutic use
  • Child
  • Follow-Up Studies
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Immunomagnetic Separation
  • Infections / chemically induced
  • Leukapheresis
  • Melphalan / therapeutic use
  • Neoplasm, Residual / diagnosis
  • Neuroblastoma / complications
  • Neuroblastoma / mortality
  • Neuroblastoma / therapy*
  • Survival Analysis
  • Transplantation, Autologous

Substances

  • Antigens, CD34
  • Busulfan
  • Melphalan