Quantitative detection of t(14;18)-positive cells in patients with follicular lymphoma before and after autologous bone marrow transplantation.
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.
Hirt
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Klinik und Poliklinik für Innere Medizin C, Haematologie und Onkologie, Ernst-Moritz-Arndt Universität Greifswald, Germany.
Dölken
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D000328:Adult; D014408:Biomarkers, Tumor; D016026:Bone Marrow Transplantation; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008224:Lymphoma, Follicular / Q000097:blood / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D014178:Translocation, Genetic; D014182:Transplantation, Autologous
D014408:Biomarkers, Tumor; D005819:Genetic Markers