Longitudinal assessment of morbidity and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation: retrospective analysis of a multicenter phase III study.

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume 15, Issue 6, p.749-56 (2009)

Keywords:

2009, Acute Disease, Center-Authored Paper, Clinical Research Division, Clinical Trials, Phase III as Topic, Cyclosporine, Drug Therapy, Combination, Follow-Up Studies, Gastrointestinal Diseases, Graft vs Host Disease, Hematologic Neoplasms, hematopoietic stem cell transplantation, Humans, Immunosuppressive Agents, Liver Diseases, methotrexate, Organ Specificity, Postoperative Complications, Public Health Sciences Division, Randomized Controlled Trials as Topic, Research Trials Office Core Facility - Biostatistics Service, Retrospective Studies, Shared Resources, Skin Diseases, Tacrolimus, Transplantation Conditioning, Transplantation, Homologous

Abstract:

Because morbidity early after hematopoietic cell transplantation (HCT) results in large part from the development of acute graft-versus-host disease (GVHD), we previously proposed that a longitudinal assessment of morbidity involving the skin, liver, and gastrointestinal (GI) tract might provide a more complete, objective approach for comparing 2 arms of open-label randomized clinical trials for acute GVHD prevention. In this study, we determined both morbidity across time and GVHD across time in a retrospective analysis of a database from an open-label randomized clinical trial comparing tacrolimus/methotrexate and cyclosporine/methotrexate after myeloablative conditioning and marrow transplantation from HLA-matched unrelated donors. The results confirm differences in overall morbidity across time in patients with peak grade II-IV GVHD compared with those with grade 0-I GVHD, but no significant differences in morbidity associated with grade II GVHD compared with grade 0-I GVHD. We observed less skin morbidity and a trend toward less liver morbidity across time in the tacrolimus group (P = .04 and .09, respectively), but not for GI morbidity or overall morbidity, despite significantly decreased skin and liver stages and overall grades of GVHD across time in this group. Thus, our objective assessment of differences in morbidity (regardless of cause) as a measure of acute GVHD in a randomized clinical trial of acute GVHD prevention has only limited utility. The difficulty of demonstrating clinical benefits from objective parameters, such as survival and morbidity, and the subjectivity of grading acute GVHD emphasize the need for blinded assessments in clinical trials of GVHD prevention.