This article reviews the current understanding of the pathogenesis of chronic graft-versus-host disease (GVHD) and its management. Chronic GVHD is an immune-mediated disorder that occurs in approximately 40% of patients after allogeneic hematopoietic cell transplantation. Chronic GVHD causes significant late morbidity and mortality and affects quality of life, survival and the risk of recurrent malignancy. The National Institutes of Health criteria for diagnosis and global severity were proposed in 2005, and their clinical usefulness has been validated. The new criteria distinguish acute and chronic GVHD by clinical manifestations and not by time after transplantation. Patients with chronic GVHD require prolonged immunosuppressive treatment. Glucocorticoids remain the standard initial treatment, but significant side effects support the need for less toxic treatment. Recently emerging strategies include expansion and maintenance of regulatory T cells to accelerate immunological tolerance, elimination of pathogenic B cells and autoantibodies, and inhibition of the pathways involving with fibrosis. Pharmacologic and non-pharmacologic approaches based on these strategies have been tested. Welldesigned prospective clinical trials based on the pathogenesis of the disease are warranted to evaluate candidate treatments and establish a new standard of care for patients with chronic GVHD.
It has been the general consensus in Japan that allogeneic peripheral blood stem cell (PBSC) donors should be hospitalized from the beginning of G-CSF administration to the end of harvest for their safety. Consequently, the admission period (about 1 week) is a heavy burden compared to bone marrow donors (3 to 4 days). Since PBSC mobilization and harvest has been successfully implemented in outpatient settings in most other countries, we think it is necessary to establish a system to deal with PBSC donors safely without admission. In Japan, since it came into service, JSHCT obliges all institutes to register all related PBSC donors on the Donor Registry Center preliminarily and it collects all the information about the donors. According to this data, 72 donors in the 25 institutes experienced G-CSF injection and PBSC harvest in outpatient settings. We sent additional questionnaires to these institutes to know the details. As a result, it was made clear that there were no severe adverse health effects, but at the same time many institutes adopted cautious stances toward the outpatient harvest system. It is important to gather these opinions and use the transplant centers' past experiences to make outpatient PBSC harvest safer for donors.
Graceptor®, a once-daily tacrolimus extended-release formulation, can be used after allogeneic hematopoietic stem cell transplantation (allo-SCT) in Japan. We retrospectively analyzed the safety and efficiency of conversion from Prograf® (tacrolimus twice-daily formulation) to Graceptor® in 13 patients presenting mild to moderate graft versus host disease (GVHD) after allo-SCT. Oral administration of Prograf® was converted to Graceptor at 62 to 5421 days after allo-SCT (median, 371 days). No complications associated with conversion were documented, and trough value to dose ratio of tacrolimus showed no significant difference between the 2 formulations. Renal function significantly improved after the conversion, even though the trough values were the same. Serum uric acid level decreased in accordance with renal function recovery. As for GVHD after the conversion, a new lesion developed in 1 case, but GVHD lesions improved in 12 cases. Recurrence was observed in 1 case. Our data show the safety and efficiency of conversion to Graceptor® after allo-SCT, particularly in patients with chronic renal failure due to tacrolimus administration.