Recurrence of Bcl-2/IgH polymerase chain reaction positivity following a prolonged molecular remission can be unrelated to the original follicular lymphoma clone

Marco Ladetto, Barbara Mantoan, Irene Ricca, Monica Astolfi, Daniela Drandi, Mara Compagno, Sonia Vallet, Maria Dell'Aquila, Alda Alfarano, Paola Rossatto, Alberto Rocci, Umberto Vitolo, Paolo Corradini, Mario Boccadoro, Corrado Tarella

Research output: Contribution to journalArticle

Abstract

Objective. The aim of this study was to evaluate whether reappearance of polymerase chain reaction (PCR) positivity for the Bcl-2/IgH translocation following a phase of molecular remission in autografted follicular lymphoma (FL) patients is always associated with reappearance of the original neoplastic clone. Patients and methods. The molecular follow-up of 119 autografted Bcl-2/IgH positive patients was evaluated by nested PCR. In case of molecular recurrence, direct sequencing of involved rearrangements has been performed both at diagnosis and at the time of recurrence. The two sequences then were compared in terms of breakpoints, N insertions, and JH usage. Results. Seventy-five patients achieving molecular remission were identified in our patient sample (63%). Of these patients, eight (10.6%) experienced molecular recurrence. Direct sequencing of the Bcl-2/IgH translocation performed at diagnosis and recurrence showed identical rearrangements in six subjects and unrelated rearrangements in two. As opposed to most true molecular relapses, unrelated rearrangements always occurred several years after transplantation. To date, the two subjects carrying unrelated rearrangements show no signs of active lymphoproliferative disease. Conclusions. This report is the first evidence that Bcl-2/IgH rearrangements unrelated to the original tumor clone can lead to false-positive results during the molecular follow-up of autografted FL patients. Based on these results, we recommend confirmation by direct sequencing, at least for patients experiencing molecular relapse 2 or more years after the end of treatment. This will be particularly important for patients enrolled in clinical trials that schedule additional treatment in case of molecular evidence of persistent disease activity.

Original languageEnglish
Pages (from-to)784-788
Number of pages5
JournalExperimental Hematology
Volume31
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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    Ladetto, M., Mantoan, B., Ricca, I., Astolfi, M., Drandi, D., Compagno, M., Vallet, S., Dell'Aquila, M., Alfarano, A., Rossatto, P., Rocci, A., Vitolo, U., Corradini, P., Boccadoro, M., & Tarella, C. (2003). Recurrence of Bcl-2/IgH polymerase chain reaction positivity following a prolonged molecular remission can be unrelated to the original follicular lymphoma clone. Experimental Hematology, 31(9), 784-788. https://doi.org/10.1016/S0301-472X(03)00191-7