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Sclerodermatous chronic GVHD in patients receiving tyrosine kinase inhibitors after allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 50, pages 139–141 (2015)Cite this article

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Chronic GVHD (cGVHD) is a major cause of morbidity and late non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT).1 Sclerodermatous chronic GVHD (scGVHD) is a distinct form of cutaneous GVHD with predominant involvement of the skin, SC tissue and fascia without visceral or vasomotor involvement, and is generally refractory to standard therapies.2 Patients with scGVHD have elevated levels of agonistic antibodies against the PDGF receptor and transforming growth factor-β, leading to the activation of these intracellular pathways.3 Imatinib, a first-generation tyrosine kinase inhibitor (TKI), exerts selective dual inhibition of both transforming growth factor-β and PDGF pathways. In addition, imatinib reduces synthesis of extracellular matrix proteins COL1A1, COL1A2 and fibronectin in cultured dermal fibroblasts derived from patients with scGVHD.4 Both imatinib and dasatinib have been used to treat patients with steroid refractory scGVHD with promising early results,4, 5, 6 including correlation with a decline in agonistic PDGFR-α antibodies as measured by a functional fibroblast bioassay.7 Based on these observations, we hypothesized that patients exposed to TKI therapy post-HCT would have a decreased incidence of later developing scGVHD.

We retrospectively analyzed the City of Hope database for patients with Ph+ ALL and CML undergoing allogeneic HCT between 2005 and 2010. Eighty-nine consecutive patients were identified, 48 Ph+ ALL and 41 CML. Patient and treatment characteristics are shown in Table 1. All patients received mobilized PBSCs. The median CD34+ cell dose was 5.9 × 106/kg (1.5–17.3 × 106/kg). Most patients received a tacrolimus/sirolimus-based GVHD prophylaxis (82%), with anti-thymocyte globulin used in 10 patients.

Table 1 Patient and treatment characteristics and outcomes (N=89)
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Acknowledgements

This work was supported in part by a P30 grant from the National Cancer Institute of the National Institutes of Health, grant #CA33572.

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Authors and Affiliations

  1. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA,

    A Salhotra, S H Thomas, P Parker, S J Forman & R Nakamura

  2. Department of Biostatistics, City of Hope, Duarte, CA, USA

    N Tsai & T Paris

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  1. A Salhotra
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  2. N Tsai
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Correspondence to R Nakamura.

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Salhotra, A., Tsai, N., Thomas, S. et al. Sclerodermatous chronic GVHD in patients receiving tyrosine kinase inhibitors after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 50, 139–141 (2015). https://doi.org/10.1038/bmt.2014.210

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