Minimal residual disease in peripheral blood stem cell harvests from high-risk neuroblastoma patients.
OBJECTIVE
We investigated whether detection of minimal residual disease (MRD) in peripheral blood stem cells (PBSC) by using tyrosine hydroxylase (TH) expression could predict outcome of patients with advanced neuroblastoma.


METHODS
Quantitative real time polymerase chain reaction was performed for the detection of tumor contamination using TH messenger ribonucleic acid (mRNA) and correlated to clinical parameters and outcome in 45 high-risk neuroblastoma patients.


RESULTS
High TH expression was detected in PBSC harvests obtained from 26 out of 45 (58%) patients. We did not find a significant correlation between MYCN status, DNA index or primary tumor site, and the TH mRNA level. Patients harboring high TH expression had reduced progression-free survival (PFS) (23%) versus those with low/negative TH expression (43%), although these results were not statistically significant. No significant correlation was observed between TH expression and overall survival.


CONCLUSIONS
The correlation between an unfavorable outcome and high TH expression in patients' PBSC harvests was not significant. This indicates a need to increase sample size in a long-term clinical outcome study to clarify the importance of TH mRNA contamination in PBSC.
Avigad
Smadar
S
Molecular Oncology, Felsenstein Medical Research Center, Tel Aviv University, Tel Aviv, Israel. savigad@post.tau.ac.il
Feinberg-Gorenshtein
Galina
G
Luria
Drorit
D
Jeison
Marta
M
Stein
Jerry
J
Grunshpan
Anna
A
Sverdlov
Yacov
Y
Ash
Shifra
S
Yaniv
Isaac
I
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000071447:N-Myc Proto-Oncogene Protein; D018365:Neoplasm, Residual / Q000175:diagnosis; D009447:Neuroblastoma / Q000097:blood* / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014446:Tyrosine 3-Monooxygenase