Abstract
Neuroblastoma is the most common extracranial solid tumor of young children. Despite advances in therapy the survival of disseminated neuroblastoma still carries a poor prognosis. Autologous transplantation of stem cells has become a promising treatment in such patients.
An accurate control of transplant is necessary to minimize the risk of tumor cell contamination.
For the detection of tumor cells in bone marrow, peripheral blood, and stem cell preparations, we established reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify tyrosine hydroxylase (TH) mRNA.
Samples from 6 pediatric patients with stage IV neuroblastoma were studied. Urinary vanillyl mandelic acid, homovanillic acid and dopamine levels were analyzed at diagnosis in all cases. Secretion of catecholamines was shown in all patients (one of these with slightly elevated dopamine); TH expression was detectable in tumor tissues and/or bone marrow aspirates. At the time of leukapheresis in all cases no contaminating neuroblastoma cells were found in PBSCs.
The high sensitivity and specificity of the RT-PCR suggest that this method is of considerable clinical value in
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1.
detecting minimal bone marrow metastasis,
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2.
monitoring of MRD (minimal residual disease) following chemotherapy to evaluate the efficacy of treatment regimens, and
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3.
assessing the effectiveness of stem cell purging in the process of autologous stem cell transplantation in neuroblastoma.
The Study was supported by the Vereine Hilfe für Krebskranke Kinder Frankfurt eV
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References
Brodeur GM, Seeger RC, Barrett A, Berthold F, Castleberry RP, D’Angio G, De Bernardi B, Evans AE, Favrot M, Freeman AI, Haase G, Hartmann O, Hayes FA, Helson L, Kemshead J, Lampert F, Ninane J, Ohkawa H, Philip T, Pinkerton CR, Pritchard J, Sawada T, Siegel S, Smith EI, Tsuchida Y, Voute PA (1988) International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol 6:1874–1881
Brugger W, Bross KJ, Glatt M, Weber F, Mertelsmann R, Kanz L (1994) Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood 83:636–640
Burchill SA, Bradbury FM, Smith B, Lewis IJ, Selby P (1994) Neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA. Int J Cancer 57:671–675
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thio-cyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Christ WM, Kun LE (1991) Common solid tumors of childhood. New Engl J Med 324:461–471
Evans AE, D’Angio GJ, Randolph J (1971) A proposed staging for children with neuroblastoma. Cancer 27:374–378
Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1987) Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochem Biophys Res Commun 146:971–975
Kurado T, Saeki M, Nakano M, Mizutani S (1997) Clinical application of minimal residual neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction. J Ped Surg 32:69–72
Ladenstein R, Lasset C, Hartmann O, Klingebiel T, Bouffet E, Gadner H, Paolucci P, Burdach S, Chauvin F, Pinkerton R, Philip T (1994) Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: Report from the European Group for Bone Marrow Transplantation. Bone Marrow Transplant 14:37–46
Mattano L, Moss TJ, Emerson SG (1992) Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res 52:4701–4705
Matthay KK, Atkinson JB, Stram DO, Selch M, Reynolds CP, Seeger RC (1993) Pattern of relapse after autologous purged bone marrow transplantation for neuroblastoma: A Children Cancer Group pilot study. J Clin Oncol 11:2226–2233
Miyajima Y, Horibe K, Fukuda M, Matsumoto K, Numata S, Mori H, Kato K (1996) Sequential detection of tumor cells in the peripheral blood and bone marrow of patients with stage IV neuroblastoma by the reverse transcriptase-polymerase chain reaction for tyrosine hydroxylase mRNA. Cancer 77:1214–1219
Naito H, Kuzumaki N, Uchino J, Kobayashi R, Shikano T, Ishikawa Y, Matsumoto S (1991) Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction. Eur J Cancer 27:762–765
Shapiro B, Gross MD (1987) Radio chemistry, biochemistry, and kinetics of 131 I-metaiodo-benzylguanidine (MIBG) and 123 I-MIBG: Clinical implications of the use of 123 I-MIBG. Med Ped Oncol 15:170–177
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© 2000 Springer-Verlag Berlin Heidelberg
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Niegemann, E. et al. (2000). Detection of Residual Tumor Cells by RT-PCR for Tyrosine Hydroxylase mRNA. In: Berdel, W.E., et al. Transplantation in Hematology and Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59592-9_23
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DOI: https://doi.org/10.1007/978-3-642-59592-9_23
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64041-4
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