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  • Letter to the Editor
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Development of severe sclerotic chronic GVHD during treatment with dasatinib

Bone Marrow Transplantation volume 45, pages 1469–1470 (2010)Cite this article

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In the recently published letter to the editor, Breccia et al.1 described a Philadelphia chromosome positive (Ph+) CML patient who relapsed after haploidentical BMT, and in whom low-dose dasatinib restored the molecular response and improved hepatic chronic GVHD (cGVHD). Moreover, several other recent papers described patients with various fibrotic/sclerotic cGVHD manifestations benefiting from imatinib.2, 3, 4 Stadler et al.5 proposed that stronger effects in cGVHD-induced fibrosis might be possible with the newer tyrosine kinase inhibitors (TKIs).

Dasatinib is a second-generation multitarget TKI approved for treatment of Ph+ CML adult patients who are resistant or intolerant to imatinib.6 Dasatinib is 325-fold more potent than imatinib against unmutated bcr-abl, but also inhibits platelet-derived growth factor receptor, c-Kit, the Src family of kinases, binds to other tyrosine and serine/threonine kinases6, 7 and may have significant antifibrotic potential,7 which would be of interest when developing new therapeutics for cGVHD. c-Abl and Src kinases are important regulators of extracellular matrix synthesis,7 and inhibition of Src signaling prevented experimental dermal fibrosis.8 c-Abl has also recently been implicated in TGF-β-associated fibrosis,7, 9 and blockade of TGF-β or PDGF reduces fibrosis in experimental models.3, 4, 7, 8, 9 Dasatinib's ability to target T-cell signaling and enhance the inhibitory effect of cyclosporine suggests an additional rationale for its use in cGVHD treatment.10

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References

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Acknowledgements

This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors are employees of the United States Government, and, as such, this work was done in that capacity. The views expressed do not necessarily represent the views of the National Institutes of Health or the United States Government.

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Authors and Affiliations

  1. Experimental Transplantation and Immunology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    D Pulanic, M R Bishop & S Z Pavletic

  2. Dermatology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    E W Cowen

  3. Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    K Baird

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  1. D Pulanic
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Correspondence to D Pulanic.

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Pulanic, D., Cowen, E., Baird, K. et al. Development of severe sclerotic chronic GVHD during treatment with dasatinib. Bone Marrow Transplant 45, 1469–1470 (2010). https://doi.org/10.1038/bmt.2009.368

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