Annals of Oncology Advance Access originally published online on February 13, 2008
Annals of Oncology 2008 19(6):1172-1179; doi:10.1093/annonc/mdn017
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hematologic malignancies |
Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC)
1 Immune and Gene Therapy Laboratory, Cancer Centre Karolinska
2 Departments of Hematology and Oncology, Karolinska University Hospital, Solna
3 Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden
4 Department of Immunology, Semnan Medical University, Semnan, Iran
* Correspondence to: Prof H. Mellstedt, Department of Oncology, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46-8-51774308; Fax: +46-8-318327; E-mail: hakan.mellstedt{at}karolinska.se
Background: Circulating myeloma cells (CMC), exhibiting the same immunoglobulin heavy-chain gene rearrangements as the plasma cells, are part of the myeloma clone. In this study, we evaluated the effect of idiotype (Id) vaccination on CMC.
Patients and methods: Eleven patients were immunized with the autologous Id in combinations with granulocyte–macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id-specific T cells were monitored by proliferation assay, enzyme-linked immunospot (interferon-
) assay, and quantitative real-time PCR for cytokines. Regulatory T (Treg) cells were analyzed by flow cytometry.
Results: CMC were detected in 9 of 11 patients at start of vaccination. In four patients, CMC declined and two had a complete molecular remission. Further two patients had stable levels of CMC during follow-up, while in three patients CMC progressively increased. Six patients had a vaccine-induced Id-specific T-cell response. A significant correlation was observed between reduced/stable levels of CMC and the Id-specific T cells (P < 0.02). The frequency of Treg cells was decreased in immune responders, but increased in immune nonresponders (P < 0.05). No significant change in the serum M-protein concentration was, however, observed in any patient.
Conclusion: Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells. Further studies are warranted to analyze the clinical significance of CMC and clinical effects of Id vaccination.
Key words: circulating myeloma cells, idiotype vaccination, multiple myeloma
Received for publication August 28, 2007. Revision received January 4, 2008. Accepted for publication January 7, 2008.