Graft vs. host disease: pathology, prophylaxis and therapy: GVHD overview.

The dominant complication limiting the effectiveness and safety of allogeneic hematopoietic cell transplantation (HCT) is graft vs. host disease (GVHD). It induces early peritransplant morbidity from organ toxicity and infection and is the most common cause of late non-relapse mortality. The hazards of acute and chronic GVHD must be addressed through prophylaxis, evaluation and therapy in all allotransplants. In this volume, we review numerous aspects of its experimental and clinical pathophysiology. The target organs, cellular tissues and molecular pathogenesis of the syndromes are highlighted to distinguish important known and still unknown differences between acute and chronic GVHD. Additionally, its prophylaxis, clinical epidemiology and impact on survival following conventional transplants and after cellular lymphoid infusions are described. Though not fully based in pathophysiology and not grounded in high-quality evidence, both conventional and new treatments for acute GVHD and the divergence of GVHD from the favorable therapeutic anti-tumor effects of an allograft are discussed. Chronic GVHD, the least understood component of the syndrome has the broadest and most widely varying presentation. The diagnosis and clinical manifestations, approaches to prophylaxis and its treatment are discussed in three descriptive clinical chapters while chronic GVHD as an autoimmune syndrome is highlighted to draw distinctions between its pathophysiology and manifestations from the classical autoimmune syndromes. The care of patients with GVHD remains a challenge well beyond management of their GVHD-specific symptoms. Several chapters outline critical elements of supportive care, late effects and their impact on quality of life are intimately tied to their immunodeficiency and risks of infection. Finally, uncertainties and variability in the physiology and clinical components of the GVHD syndrome yield complexity in its clinical study and endpoints suitable for analysis. Outlines of these topics and challenges for their future are described to develop a future research agenda for the HCT community. We remember that although GVHD has plagued transplant recipients and challenged transplant physicians for many years, newer pre-clinical, clinical and investigative models yield hope and excitement that harness the allogeneic anti-neoplastic plastic power will not always be confounded by the symptomatology of GVHD. Its continuing