Long-term results of CD34(+) cell transplantation in children with neuroblastoma.
BACKGROUND
This is the first report of the long-term results of CD34(+) cell transplantation in children with neuroblastoma. We investigated the hematologic and immune recovery, posttransplant morbidity, and clinical outcome of these children.


METHODS
Twenty-three children with advanced neuroblastoma had PBPCs (20 patients) or BM (3 patients) collected, followed by CD34(+) cell selection on Ceprate column. The purge of residual neuroblastoma cells was evaluated using an RT-PCR for tyrosine hydroxylase (TH) mRNA assay. Reinfusion of CD34(+) cells followed busulfan + melphalan myeloablative chemotherapy.


RESULTS
A median of 2.9 x 10(6) CD34(+) cells/kg was reinjected. Median days to achieve ANC > 0.5 x 10(9)/liter and platelets > 50 x 10(9)/liter were 13 (range 9-33) and 59 (range 22-259), respectively. Circulating T cells were primarily CD4(-)/CD8(+) with fewer than 0.2 10(9)CD4(+) cells/liter throughout the first 6 months. CD19(+) cells and CD56(+) cells were not detectable up to day +35 posttransplant. At 1 year posttransplant, 16 evaluable patients had stable hematopoiesis with 2.3 x 10(9) ANC/liter (range 0.8-4.1), 1.4 x 10(9) lymphocytes/liter (range 0.5- 2.0) and 251 x 10(9) PLT/liter (range 35-490). After the completion of hematopoietic reconstitution, six events of severe septicemia/septic shock were noted. Six children had severe VZV infections, and 2 had EBV-associated lymphoproliferation. Thirteen patients are alive with a median follow-up of 40 months (range 2-54). Ten patients have died; 8 relapsed or developed progressive disease, 1 died from nondocumented pneumopathy at day 56, and 1 developed AML-M4 at 3 years posttransplant.


CONCLUSIONS
In children, CD34(+) cell transplantation can be accomplished with a reduction of neuroblastoma cell inoculum in the selected graft as assessed by RT-PCR analysis. CD34(+) cell grafts provide successful neutrophil reconstitution. However, delayed platelet recovery, persistent decrease in CD4(+) lymphocyte levels and a high incidence of serious and life-threatening late infections were observed in these children. There remains a critical need to evaluate any real clinical benefit of CD34(+) cell autografts in neuroblastoma patients.
Kanold
J
J
Unité Bioclinique de Prélèvement et de Traitement des Cellules Hématopoïétiques, Pédiatrie B, Clermont-Ferrand, France.
Yakouben
K
K
Tchirkov
A
A
Carret
A S
AS
Vannier
J P
JP
LeGall
E
E
Bordigoni
P
P
Deméocq
F
F
D018952:Antigens, CD34 / Q000032:analysis* / Q000276:immunology; D019046:Bone Marrow Neoplasms / Q000401:mortality / Q000628:therapy; D016026:Bone Marrow Transplantation; D001859:Bone Neoplasms / Q000401:mortality / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005602:France / Q000453:epidemiology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy; D008297:Male; D009447:Neuroblastoma / Q000401:mortality* / Q000628:therapy*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D017741:Survivors
D018952:Antigens, CD34