Clinical and molecular follow-up by amplification of the CDR-III IgH region in multiple myeloma patients after autologous transplantation of hematopoietic CD34+ stem cells

Giovanni Martinelli, Carolina Terragna, Roberto M. Lemoli, Michele Cavo, Monica Benni, Maria Rosa Motta, Marilina Amabile, Emanuela Ottaviani, Nicoletta Testoni, Antonio De Vivo, Sante Tura

Research output: Contribution to journalArticle

Abstract

Background and Objective. Autologous blood stem cell transplantation (ABSCT) using chemotherapy-induced mobilization of peripheral blood stem cells (PBSC) is being increasingly used in the treatment of multiple myeloma (MM). We report the clinical and molecular follow-up of 10 MM patients who underwent autologous stem cell transplantation with peripheral blood selected CD34+ cells, as support therapy following a myeloablative conditioning regimen. Design and Methods. The CDR-III coding region of the IgH gene was studied by a) consensus PCR applied to 8 MM patients, or b) by direct sequencing of PCR product generated by family-specific primers in the remaining two patients (who became immunofixation analysis (IF) negative). In this case, two patient-specific primers were generated, thus obtaining a high PCR assay sensitivity and specificity (ASO PCR). Results. Seven patients are alive: 4 of them have serum M protein assessable by IF, while 1 was not a secretor and 2 converted from serum IF positivity to negativity 6 and 12 months after ABSCT. Three patients died: 1 from disease progression and 2 from infective complications during clinical remission. The molecular analysis during the follow-up showed that the bone marrow samples from the two patients who obtained IF negativity were persistently PCR positive for the presence of rearranged CDR-III region. Moreover, despite the remarkable reduction of myeloma burden, a minimal level of residual myeloma cells was still detectable by molecular analysis. Interpretation and Conclusions. These results confirm that although positive selection of CD34+ cells markedly reduces the contamination of myeloma cells from apheresis products by up to 3 log, and provides a cell suspension capable of restoring normal hematopoiesis after ablative conditioning regimen, it does not abrogate myeloma cell contamination in most of the apheresis products.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalHaematologica
Volume84
Issue number5
Publication statusPublished - 1999

Keywords

  • ABMT
  • CD34 cells
  • Minimal residual disease
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology

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    Martinelli, G., Terragna, C., Lemoli, R. M., Cavo, M., Benni, M., Motta, M. R., Amabile, M., Ottaviani, E., Testoni, N., De Vivo, A., & Tura, S. (1999). Clinical and molecular follow-up by amplification of the CDR-III IgH region in multiple myeloma patients after autologous transplantation of hematopoietic CD34+ stem cells. Haematologica, 84(5), 397-404.