Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma.
BACKGROUND
Despite treatment with high-dose myeloblative chemotherapy and peripheral blood stem cell (PBSC) rescue, a high proportion of children with neuroblastoma relapse and die. Re-infusion of PBSC contaminated with tumour at the time of autologous transplantation may play a significant role in this relapse. In this study the frequency of tumour contamination in PB from children with neuroblastoma has been investigated.


METHODS
Minimal residual disease was measured using RT-PCR for tyrosine hydroxylase (TH) mRNA in PBSCs from patients with advanced neuroblastoma. PBSCs from 18 patients in complete clinical remission were studied.


RESULTS
Studies in other cancers have suggested minimal contamination of PBSCs with tumour cells; TH mRNA was detected by RT-PCR in 50% (9/18) of PBSC harvests. Seventy-seven percent (7/9) of patients with TH mRNA in PBSC died of disease compared to 44% (4/9) who were TH mRNA-negative.


CONCLUSIONS
Therefore, the presence of TH mRNA in PBSCs appeared to be associated with an unfavourable outcome, although this was not statistically significant. In summary, RT-PCR for TH mRNA is a sensitive method for the identification of tumour cells in PBSC harvest. The presence of TH mRNA in PBSC harvest may reflect disease status and be associated with an unfavourable outcome, although long-term clinical outcome studies in a larger patient cohort are required.
Burchill
S A
SA
Candlelighter's Children's Cancer Research Laboratory, St. James's University Hospital, Leeds, United Kingdom. S.A.Burchill@leeds.ac.uk
Kinsey
S E
SE
Picton
S
S
Roberts
P
P
Pinkerton
C R
CR
Selby
P
P
Lewis
I J
IJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D015993:Life Tables; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood* / Q000235:genetics; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014182:Transplantation, Autologous / Q000009:adverse effects*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000737:chemistry; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014446:Tyrosine 3-Monooxygenase