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Safety and efficacy of combining ATRA with G-CSF in HSPC mobilization; a pilot study in multiple myeloma and non-Hodgkin's lymphoma patients

Bone Marrow Transplantation volume 40, pages 801–803 (2007)Cite this article

High-dose therapy and hematopoietic stem and progenitor cell (HSPC) transplantation have dramatically improved survival in a wide range of malignancies.1 Treatment is contingent upon mobilization of adequate numbers of HSPC. Mobilization failure affects 5% of normal healthy donors, 20–30% of all cancer patients and more than 60% of fludarabine-exposed patients.1, 2 Therefore, strategies to improve HSPC mobilization are necessary.

Proteases derived from neutrophils are central to the mechanism of granulocyte-colony-stimulating factor (G-CSF) mobilization of HSPC. Preclinical data demonstrate G-CSF-induced protease-dependent cleavage of the intercellular adhesive interactions which ‘home’ HSPC to the bone marrow (BM).3 We have demonstrated that the granulocyte-differentiating properties of two retinoids—VTP195183 (a novel highly specific retinoic acid receptor alpha (RARα) agonist) and all trans-retinoic acid (ATRA, a pan-RAR agonist)—can be exploited in mobilization. These agents synergized with G-CSF to enhance peripheral blood (PB) HSPC content in both a ‘poor mobilizer’ and ‘good mobilizer’ murine model.4 We sought to determine whether these findings would translate into the human setting; however, there are limited safety data on combining retinoids with G-CSF in humans.

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Acknowledgements

This study was supported by grants from the Leukemia and Lymphoma Society (US) (to KEH and HMP), the Max Whiteside Fellowship from the Leukaemia Foundation of Victoria (to KEH), the AMP Clinical Fellowship from the Leukaemia Foundation of Victoria (to KEH) and the Haematology Society of Australasia and New Zealand Scholarship (to KEH).

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Authors and Affiliations

  1. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    K E Herbert, S True, G McArthur & H M Prince

  2. Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia

    K E Herbert, G McArthur & H M Prince

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  1. K E Herbert
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  2. S True
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  3. G McArthur
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  4. H M Prince
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Correspondence to K E Herbert.

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Herbert, K., True, S., McArthur, G. et al. Safety and efficacy of combining ATRA with G-CSF in HSPC mobilization; a pilot study in multiple myeloma and non-Hodgkin's lymphoma patients. Bone Marrow Transplant 40, 801–803 (2007). https://doi.org/10.1038/sj.bmt.1705804

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