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 MESSENGER-RNA

BACKGROUND. The aim of this study was to evaluate the changes of tumor cell contamination in bone marrow (BM) and peripheral blood (PB) duri ng the clinical course of patients with advanced neuroblastoma by dete cting 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 stud ied. All 15 patients had peripheral blood stem cell (PBSC) samples and BM samples examined for TH mRNA by using the reverse transcription-po lymerase chain reaction (RT-PCR) at the time of harvest. Nine of the 1 5 patients, also had BM and PB samples examined sequentially. RESULTS. Comparing the 45 paired samples concurrently drawn, 16 of 28 BM sampl es (57.1%) and 4 of 28 PB samples (14.2%) obtained during complete rem ission (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 pos itivity 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 o f 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). CONCLUSI ONS. These findings show that there is a substantial risk of tumor cel l contamination in harvested PBSCs, although its incidence was lower t han that in BM samples. We recommend that PBSCs would be better harves ted during remission and should be examined for tumor contamination be fore use as a stem cell source. (C) 1996 American Cancer Society.