Annals of Oncology Advance Access originally published online on February 28, 2005
Annals of Oncology 2005 16(4):611-617; doi:10.1093/annonc/mdi123
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© 2005 European Society for Medical Oncology
Original articles |
Molecular monitoring of tumour load kinetics predicts disease progression after non-myeloablative allogeneic stem cell transplantation in multiple myeloma
1 Department of Internal Medicine V and 2 Institute of Human Genetics, University of Heidelberg; 3 Central Unit Biostatistics, German Cancer Research Center, Heidelberg; 4 Department of Hematology and Oncology, Staedt. Kiniken Bielefeld GmbH, Germany
* Correspondence to: Dr Marc S. Raab, Department of Internal Medicine V, University of Heidelberg, INF 410, D-69120 Heidelberg, Germany. Tel: +49-6221-568072; Fax: +49-6221-565609; Email: marc.raab{at}med.uni-heidelberg.de
Background: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting.
Patients and methods: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested.
Results: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P <0.001). The detection limit amounted to 1/104–1/105 cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse.
Conclusion: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention.
Key words: IgH rearrangement, minimal residual disease, multiple myeloma, non-myeloablative allogeneic transplantation, real-time PCR