Chronic graft-versus-host disease (cGVHD) continues to be a common complication of allogeneic hematopoietic stem cell transplantation. Unlike acute graft-versus-host disease, which is mediated almost entirely by donor T cells, the immune pathology of cGVHD is more complex and donor B cells have also been found to play an important role. Recent studies from several laboratories have enhanced our understanding ofhow donor B cells contribute to this clinical syndrome and this has led to new therapeutic opportunities. Here, Dr Sarantopoulos reviews some of the important mechanisms responsible for persistent B cell activationand loss of B cell tolerance in patients with cGVHD. Dr Blazar describes recent studies in preclinical models that have identified novel B cell-directed agents that may be effective for prevention or treatment ofcGVHD. Some B cell-directed therapies have already been tested in patients with cGVHD and Dr Cutler reviews the results of these studies documenting the potential efficacy of this approach. Supported by mechanistic studies in patients and preclinical models, new B cell-directed therapies for cGVHD will now be evaluated in clinical trials.
Bibliographical noteFunding Information:
The authors thank Jing Du, Katelyn Goodman, and Drs Ryan Flynn, Jay Bradner, Jun Qi, Ari Melnick, Raphael Clynes, Alexandra Zanin-Zhorov, Jason Dubovsky, John Byrd, and Lawrence Elias for performing experiments, providing reagents and/or helpful discussions. We thank Rigel Pharmaceuticals for providing fostamatinib, Kadmon Pharmaceuticals for KD025, and Pharmacyclics for providing ibrutinib for laboratory studies. Studies described in this review were supported by NIH grants CA142106 , K08HL107756 , and AI056299 , DOD grant CA100254 , Kadmon Pharmaceuticals Inc and a translational grant from the Leukemia and Lymphoma Society of America ( LLS Grant 6458-15 ).
- B cell
- Chronic graft-versus-host disease
- Stem cell transplantation