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Blood, 1 February 2004, Vol. 103, No. 3, pp. 878-885. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-05-1400. This Article Full Text (PDF) All Versions of this Article: 2003-05-1400v1 103/3/878    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Drouet, M. Articles by Herodin, F. Search for Related Content PubMed PubMed Citation Articles by Drouet, M. Articles by Herodin, F. Social Bookmarking                   What's this? Submitted May 5, 2003 Accepted September 30, 2003 Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and Interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: long-term follow-up of hematopoiesis Michel Drouet, Frederic Mourcin, Nancy Grenier, Valerie Leroux, Josianne Denis, Jean-Francois Mayol, Philippe Thullier, Jean-Jacques Lataillade, and Francis Herodin* Department of Radiobiology, Centre de Recherches du Service de Sante des Armees, La Tronche, France Department of Immunology, Centre de Transfusion Sanguine des Armees, Clamart, France * Corresponding author; email: Francis.Herodin{at}wanadoo.fr. Preservation of hematopoietic stem and progenitor cell survival is required for recovery from radiation-induced myelosuppression. We recently showed that short-term injection of antiapoptotic cytokine combinations to mice soon after lethal gamma-irradiation promoted survival. The present study investigated the hematopoietic response of cynomolgus monkeys to a single dose of Stem Cell Factor, FLT3-Ligand, Megakaryocyte Growth and Development Factor and Interleukin-3 in combination (4F, each factor given intravenously at 50µ/kg) administered 2 hours after 5 Gy gamma-irradiation. Treated monkeys (n=4) experienced no thrombocytopenia. Only one in four displayed a transient period of neutropenia (ANC<500/µL) whereas all irradiated controls (n=4) experienced neutropenia (5 to 12 days) and thrombocytopenia (PLT<20,000/µL: 5 to 31 days). Treated animals exhibited an impressive two-wave PLT response that peaked at Day 8 and 22 post TBI. Areas under the curve of PLT, ANC, WBC and RBC between Day 0 and 90 were significantly higher in treated animals than in controls. Humeral bone marrow-derived clonogenic activity was significantly spared at 24 hours and 4 days post TBI in treated monkeys. No apparent impairment of the hematopoietic status and stem cell pool, in terms of LTC-IC and SP cells, was observed after 15 months. These results strongly suggest that the 4F cytokine combination, as a single dose regimen could act as an emergency treatment for nuclear accident or terrorism victims. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Drouet, C. Delaunay, N. Grenier, P. Garrigou, J.-F. Mayol, and F. Herodin Cytokines in combination to treat radiation-induced myelosuppresssion: evaluation of SCF + glycosylated EPO + pegylated G-CSF as an emergency treatment in highly irradiated monkeys Haematologica, March 1, 2008; 93(3): 465 - 466. [Abstract] [Full Text] [PDF]

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