A pilot study of low‐dose cyclosporin for graft‐versus‐host prophylaxis in marrow transplantation

Abstract

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.

Association between pretransplant Thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors

“…Two previous trials comparing initial CsA doses of 1.5 vs 3.0 mg/kg/day, or 1.0 vs 5.0 mg/kg/day found no differences in the non-relapse mortality rates. 34,35 Therefore, differences in TBI dose fractionation or initial CsA dose were probably not the reason for the lower non-relapse mortality in the study cohort.…”

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

“…CSP inhibits canalicular bile transport at pharmacologic doses in a dose-related manner 39 and commonly causes increases in serum bilirubin levels. 40 At very high blood levels, CSP can result in liver injury with hepatocyte necrosis and elevated serum hepatic aminotransferase enzyme levels. Patients with acute liver GVHD may have impaired elimination of CSP, 41 and, in addition, CSP may contribute to compromised renal function, reducing the renal clearance of conjugated bilirubin and resulting in further elevation of total serum bilirubin level out of proportion to the degree of underlying liver dysfunction.…”

Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

“…For unrelated donor transplants, the incidence of grade II-IV acute GVHD (55%) was similar to published adult trials by Nash et al, 19 and Devine et al 21 When compared to published reports using cyclosporine and methotrexate as prophylaxis for acute GVHD, the current therapy with tacrolimus and methotrexate appears at least as efficacious. [39][40][41][42][43][44] However, there are few reports that examine the use of cyclosporine plus short course methotrexate in a strictly pediatric population (р16 years). Peters et al 42 recently noted the wide variation in cyclosporin prophylaxis that is currently in use in pediatric stem cell transplantation.…”