More than skin deep? Emerging therapies for chronic cutaneous GVHD

Abstract

The options for treating skin disease after haemopoietic progenitor cell transplant (HPCT) have broadened considerably over the last decade to include much more than topical steroids and emollients. This article reviews current and emerging therapies for chronic cutaneous GVHD, a well-recognised complication of HPCT. Alongside skin-directed therapies, there is now a wide range of systemic agents with differing targets for which an evidence base is emerging. Of particular interest, we summarise the role of electrocorporeal photopheresis, a therapy increasingly used in the United Kingdom to treat severe sclerodermoid manifestations of GVHD. We include a discussion of the expanding knowledge of the pathogenesis of cutaneous GVHD, which is informing our understanding and development of second line therapies (for example, the role of B cells and the utility of rituximab). Additionally, we draw attention to challenges encountered in the evaluation of chronic GVHD treatments and highlight recommendations for further research that may enable haematologists and dermatologists to provide better care for these patients. Finally, we present a clinical algorithm to aid the approach to treating limited and extensive disease and steroid refractory or persistent disease where steroid sparing may be necessary.

Chronic graft‐versus‐host disease of the male genitalia: an underrecognized manifestation

“…Hinsichtlich der Pathogenese der cGVHD sind nicht nur Th1-, Th2-, Th17-und B-Zellen beteiligt, aufgrund der durch autoreaktive CD4+-Zellen beeinträchtigten T-Zell-Selektion im Thymus kommt es zu einer Depletion regulatorischer T-Lymphozyten [ 3,4 ] .…”

Crowdsourcing to delineate skin affected by chronic graft‐vs‐host disease

“…Chronic GVHD is the leading cause of nonrelapse long‐term morbidity and mortality in hematopoietic stem cell transplantation (HCT) patients . Skin is the most commonly affected organ in cGVHD, resulting in distressing patient morbidity. Cutaneous disease burden is strongly associated with survival, and so is often used as the primary endpoint metric in large multicenter trials .…”

Limited Impact of Imatinib in a Murine Model of Sclerodermatous Chronic Graft-versus-Host Disease

“…However, imatinib is not specific towards BCR-ABL and also targets other tyrosine kinases such as the stem cell factor c-kit, c-Abl (involved in transforming growth factor (TGF)-β signaling pathway), and platelet-derived growth factor receptor (PDGF-r) [22]. Given that the TGF-β and PDGF signaling pathways are largely involved in the fibrogenesis process in scl-cGVHD [15, 23], and given the ability of imatinib to inhibit T-cell proliferation in vitro [24], some clinical studies have assessed the impact of imatinib in patients with steroid-refractory cGVHD [25–29]. Unfortunately, these studies yielded conflicting results underlying the importance of re-assessing the impact of imatinib in scl-cGVHD in pre-clinical models.…”