CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma.
BACKGROUND
Graft contamination has been blamed for causing relapse in children with high-risk neuroblastoma (HRNB) after autologous hematopoietic stem cell transplantation (HSCT).


METHODS
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.
Institut d'Hématologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France. marabell@lyon.fnclcc.fr
Aurélien
A
Marabelle
Etienne
E
Merlin
Pascale
P
Halle
Catherine
C
Paillard
Marc
M
Berger
Andrei
A
Tchirkov
Raphaël
R
Rousseau
Guy
G
Leverger
Christophe
C
Piguet
Jean-Louis
JL
Stephan
François
F
Demeocq
Justyna
J
Kanold
D018952:Antigens, CD34; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D005500:Follow-Up Studies; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D018189:Immunomagnetic Separation; D007239:Infections / Q000139:chemically induced; D007937:Leukapheresis; D008558:Melphalan / Q000627:therapeutic use; D018365:Neoplasm, Residual / Q000175:diagnosis; D009447:Neuroblastoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D002066:Busulfan; D008558:Melphalan