Chronic Graft-Versus-Host Disease after Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplantation. A Pediatric Blood and Marrow Transplant Consortium Study..

Chronic graft versus host disease (GVHD) is a significant cause of morbidity and mortality in matched unrelated donor hematopoietic stem cell transplantation. Incidence of acute GVHD is a major risk factor for chronic GVHD. Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. When comparing cyclosporine to tacrolimus for GVHD prophylaxis, we previously reported a trend toward superiority of cyclosporine as prophylaxis against acute GVHD. We now analyze their effect on the incidence and severity of chronic GVHD. In a multi-institutional trial, we prospectively collected the clinical data on 141 evaluable patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 60.1% of patients received cyclosporine and 39.9% of patients received tacrolimus. Rates for acute GVHD were 60.4% for cyclosporine and 73.8% for tacrolimus (p = 0.086). Rates for chronic GVHD were 44.2% for cyclosporine and 47.3% for tacrolimus (p = 0.7). In the 61 patients with chronic GVHD, extensive disease was present in 82.9% of cyclosporine group and 80.8% of the tacrolimus group (p = 1.0) Those graded as moderate or severe comprised 80% of the cyclosporine group and 56% of the tacrolimus group (p = 0.46) and those both extensive and moderate or severe were 71.4% and 52%, respectively (p = 0.12). In pediatric matched unrelated donor transplantation, the incidence and severity of chronic graft versus host disease in patients receiving either tacrolimus/methotrexate or cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.