Sequential detection of tumor cells in the peripheral blood and bone marrow of patients with stage IV neuroblastoma by the reverse transcription-polymerase chain reaction for tyrosine hydroxylase mRNA.

BACKGROUND

The aim of this study was to evaluate the changes of tumor cell contamination in bone marrow (BM) and peripheral blood (PB) during the clinical course of patients with advanced neuroblastoma by detecting tyrosine hydroxylase (TH) mRNA to clarify the appropriate source and time for harvesting hematopoietic stem cells for transplantation.

METHODS

A total of 15 patients with Stage IV neuroblastoma were studied. All 15 patients had peripheral blood stem cell (PBSC) samples and BM samples examined for TH mRNA by using the reverse transcription-polymerase chain reaction (RT-PCR) at the time of harvest. Nine of the 15 patients, also had BM and PB samples examined sequentially.

RESULTS

Comparing the 45 paired samples concurrently drawn, 16 of 28 BM samples (57.1%) and 4 of 28 PB samples (14.2%) obtained during complete remission (CR) were positive for TH mRNA (P < 0.01), whereas 17 of 17 BM samples (100%) and 14 of 17 PB samples (82.3%) obtained before CR was achieved were positive (not significant). The incidence of TH mRNA positivity was significantly lower in the samples obtained during CR than those obtained before CR was achieved (P < 0.0001 for PB samples, P < 0.01 for BM samples). At the time of PBSC harvesting, the incidence of TH mRNA positivity was lower in PBSC samples (3 of 15, 20%) than in BM samples obtained concurrently (10 of 15, 66.7%; P < 0.03).

CONCLUSIONS

These findings show that there is a substantial risk of tumor cell contamination in harvested PBSCs, although its incidence was lower than that in BM samples. We recommend that PBSCs would be better harvested during remission and should be examined for tumor contamination before use as a stem cell source.