Abstract
The aim of this study was to evaluate whether a quantitative analysis of circulating t(14;18)-positive cells is of prognostic significance in patients with follicular lymphoma (FL) after myelo-ablative therapy supported by ABMT. We tested DNA from primary lymphoma tissue as well as PBMC before and after ABMT from 15 patients for the presence of the t(14;18) translocation. Nine patients showed a t(14;18) translocation, six patients were t(14;18)-negative. Circulating t(14;18)-positive cells of seven patients were quantitatively determined by limiting dilution assays combined with a two-step PCR and by real-time quantitative PCR. The results of both methods correlate very well. The number of circulating t(14;18)-positive cells decreased significantly in all patients after myeloablative therapy and ABMT, t(14;18)-negative blood samples were found in five of seven patients. In all patients circulating t(14;18)-positive cells reappeared within 2 years after ABMT showing two different patterns. During continuous CR the numbers of circulating t(14;18)-positive cells were found to be stable within one order of magnitude. In contrast, in one patient the relapse was accompanied by a logarithmic increase of t(14;18)-positive cells. In a second patient the enlargement of lymph nodes developing over a period of 12 months was accompanied by very slowly increasing numbers of t(14;18)-positive cells. In all cases where diagnostic lymph node tissue was available, the same t(14;18) translocation was found at first diagnosis and after ABMT as shown by nucleotide sequence analysis. We conclude that the quantitative detection of circulating t(14;18)-positive cells during follow-up of patients with FL after ABMT reflects the clinical course of the disease. Relapses are associated with increasing numbers of circulating t(14;18)-positive cells and continuous complete remissions with stable cell counts. Bone Marrow Transplantation (2000) 25, 419–426.
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Acknowledgements
This paper is dedicated to Karl G Blume on the occasion of his 60th birthday. We gratefully acknowledge the excellent technical assistance of Marika Held and Jens Fischer. We are grateful to E Kohlund and AI Soerjanta for their help in collecting blood samples and reviewing clinical data, and to G Illerhaus and D Layer for their help in sequencing all t(14;18)-translocations ever found in our laboratory. We also thank Prof Dr HE Schaefer and Dr G Köhler (Pathol Inst, University Freiburg, Germany), Prof Dr R Parwaresch (Hämatopathol Inst, University Kiel, Germany), Prof Dr B Helpap (Path Inst, Singen, Germany) and Prof Dr H Frenzel (Path Inst, Karlsruhe, Germany) for providing formalin-fixed, paraffin-embedded tissue blocks or tissue sections for PCR analysis. They also provided histologic confirmation that the tissue block or tissue sections being used for PCR analyses contain the initially diagnosed lymphoma.
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Hirt, C., Dölken, G. Quantitative detection of t(14;18)-positive cells in patients with follicular lymphoma before and after autologous bone marrow transplantation. Bone Marrow Transplant 25, 419–426 (2000). https://doi.org/10.1038/sj.bmt.1702147
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DOI: https://doi.org/10.1038/sj.bmt.1702147
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