The role of B cell depleting therapy in graft versus host disease after allogeneic hematopoietic cell transplant

Abstract

Graft versus host disease (GVHD) remains a common complication following allogeneic hematopoietic cell transplant (HCT). Historically, research into prevention and treatment of GVHD has centered on donor T lymphocytes using strategies to suppress or deplete these cells. The role of B lymphocytes in the pathogenesis of this disease was brought to prominence following a case report of a patient with chronic GVHD who responded to B cell depletion therapy with rituximab. Since this original observation, several clinical trials and case series have been published on the use of B cell depletion using rituximab in the treatment of chronic GVHD. Corresponding to this clinical experience, considerable laboratory evidence has revealed the complex interactions between B and T cells which culminate in acute and chronic GVHD. More recently, researchers have examined the link between B cell immune reconstitution following HCT and the development of chronic GVHD. The focus of the next decade will likely be on prevention and treatment of GVHD through targeted therapies directed at key pathways in this process. This article provides an overview of the current understanding regarding the role of B cells in GVHD along with discussion on how this knowledge will be used to direct future therapies.