Outcome prediction by molecular detection of minimal residual disease in bone marrow for advanced neuroblastoma

Background. We have determined whether sequential molecular detection of mi nimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). Procedure. Bone marrow sample s from 19 patients over 12 months of age with stage 4 neuroblastoma were se quentially examined for tumor cell contamination by detecting tyrosine hydr oxylase (TH) mRNA using reverse transcription-polymerase chain reaction (RT -PCR). All patients received repetitive multi-drug chemotherapy including c isplatin, cyclophosphamide or ifosphamide, adriamycin, and etoposide or vin cristine. Seventeen patients received myeloablative therapy with hematopoie tic stem cell transplantation after achieving complete remission. Results. All but one patient were histologically positive for tumor cells in BM samp les at diagnosis, and they became negative for tumor cells within 3 months histologically. By the RT-PCR analysis, all patients were positive for TH m RNA in BM samples at diagnosis, and they became negative for TH mRNA 1 to 1 3 months after the start of chemotherapy. Six patients whose BM samples bec ame negative for TH mRNA within 4 months after the start of chemotherapy re mained alive without evidence of disease (median 61 months, range 20-76). I n contrast, 12 of 13 patients whose BM samples remained positive at that ti me developed relapse and 10 of them died of disease (median 24 months, rang e 13-43). There was a statistically significant difference in survival betw een the two groups (P < 0.05). No significant difference of clinical charac teristics by the MRD positivity at 4 months after the start of chemotherapy . Conclusions. Persistence of MRD in BM at 4 months after the star? of chem otherapy could predict poor prognosis in advanced neuroblastoma. Med. Pedia tr. Oncol. 36:203-204, 2001. (C) 2001 Wiley-Liss, Inc.