Track

Clinical Studies

Abstract

Chronic GVHD (cGVHD) is a leading cause of long-term morbidity following allogenic hematopoietic stem cell transplantation and can manifest as a scleroderma-like cutaneous fibroinflammatory disease (sclerodermatous cGVHD). First line of therapy consists of high-dose steroids, but 50 to 60% of patients will require additional therapeutics within 2 years after transplant. Diverse T cell responses have been reported to play a role in development of cGVHD although T cell signatures have not been explored as a biomarker of response to therapy. We analyzed 13 cases of steroid-refractory sclerodermatous cGVHD with available pre- and post-treatment skin biopsy specimens using duplex immunohistochemistry (Th1: CD4+Tbet+; Th2: CD4+GATA3+) to determine whether the helper T cell immune phenotype can predict clinical response to sonidegib, a hedgehog pathway inhibitor. Six patients were clinically classified as responders and 7 as non-responders. In the pre-treatment samples the average density of Th1 cells was 1.7/mm2 (1.9 in responders, 1.6 in non-responders), and Th2 cells was 2.8/mm2 (4.3 in responders, 1.4 in non-responders). Post-treatment, Th2 cell density decreased in responders (4.3 to 1.1/mm2) and increased in non-responders (1.6 vs. 4.1/mm2). The density of Th1 cells was similar pre- and post-treatment in both responders and non-responders. This work suggests that Th2 but not Th1 cells are involved in the mechanism of effect of hedgehog inhibitors in cutaneous cGVHD. As sclerodermatous cGVHD is rare, our findings are limited by small sample size. Further study in a larger cohort may guide clinical treatment decisions in steroid-refractory sclerodermatous cGVHD patients.