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Rapamycin for GVHD prophylaxis - potential for severe myelotoxicity

Bone Marrow Transplantation volume 27, page 115 (2001)Cite this article

Natural products of many bacteria and fungi have a variety of physiological effects in animals as a result of disruption of conserved signal transduction cascades.1 One of them, rapamycin, is under investigation for the prevention of graft-versus-host disease (GVHD).23 It has also been used to avert rejection in organ transplantation456 and in the treatment of psoriasis7 and rheumatoid arthritis.8 Reported toxicities include neutropenia, thrombocytopenia and anaemia.67 Studies in cell lines have demonstrated considerable growth inhibition by rapamycin in the dose range 0–10 nM but with little increase in effect at higher concentrations (10–1000 nM).9 This inhibition is believed to be the result of selective inhibition of S6 ribosomal protein kinase (p70S6K) activation thereby preventing cyclin-dependent kinase activation, retinoblastoma protein (pRB) phosphorylation and cell cycle progression.10

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  1. Department of Haematology, LRF Centre for Adult Leukaemia, Imperial College School of Medicine, Hammersmith Campus, London, UK

    RJ Davidson, SB Marley & MY Gordon

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  2. SB Marley
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Davidson, R., Marley, S. & Gordon, M. Rapamycin for GVHD prophylaxis - potential for severe myelotoxicity. Bone Marrow Transplant 27, 115 (2001). https://doi.org/10.1038/sj.bmt.1702745

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