| Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy. | |
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MedLine Citation:
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PMID: 19966210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients with multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the lymphopenia period occurring after various immunosuppressive or chemotherapy treatments may provide an interesting opportunity for adoptive antitumor immunotherapy. The objective of this study was to determine an immunotherapy window after HDM and ASCT, evaluating T cell lymphopenia, and measuring circulating immune cytokine concentrations in patients with multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30. IL-6, IL-7, and IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in IL-7 and IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without cytokine in vitro, and that addition of IL-7 or IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro. |
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Authors:
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Maud Condomines; Jean-Luc Veyrune; Marion Larroque; Philippe Quittet; Pascal Latry; Cécile Lugagne; Catherine Hertogh; Tarik Kanouni; Jean-François Rossi; Bernard Klein |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-04 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-07 Completed Date: 2010-02-08 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1079-84 Citation Subset: AIM; IM |
Affiliation:
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Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Proliferation Cell Survival / immunology Cytokines / blood* Female Hematopoietic Stem Cell Transplantation / methods Humans Immunologic Factors Immunotherapy, Adoptive Kinetics Lymphocyte Depletion / methods* Male Melphalan / pharmacology* Middle Aged Multiple Myeloma / therapy* T-Lymphocytes / cytology Transplantation, Autologous |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Immunologic Factors; 148-82-3/Melphalan |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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