High-dose cyclosporine and corticosteroids for prophylaxis of acute and chronic graft-versus-host disease.
Twenty-eight consecutive recipients of HLA-identical sibling marrow grafts received prophylaxis for GVHD with high-dose cyclosporine (CsA) and corticosteroids. CsA 5 mg/kg/day (2.5 mg/kg infused over 4 h twice daily) was started on day -1 and continued until patients could take oral CsA (15 mg/kg/day). CsA doses were adjusted to maintain concentrations between 200-800 ng/ml (whole-blood HPLC) until the tapering period (days 268-361). Methylprednisolone 0.5 mg/kg/day was started on day 7, increased to 1 mg/kg/day during days 15-28, and tapered thereafter until discontinuance on day 194. Low CsA trough levels occurred in 15 patients (54%) during the i.v. administration period. Ten patients (36%) developed grade I and 3 patients (11%) developed grade II acute GVHD; there were no cases of grade III or IV disease. The actuarial incidence of chronic GVHD was 29% at 1 year but 57% at 2 years due to development of chronic GVHD after discontinuation of immunosuppressive agents. High blood CsA concentrations in stable outpatients led to dose-limiting nephrotoxicity. Infections occurred throughout the period of extended immunosuppression (from 6 to 12 months) but were not life-threatening. The actuarial incidence of leukemic relapse was 18% at 1 year and 25% at 2 years. Actuarial survival at 1 and 2 years was 68 and 51%, respectively. Despite the frequent occurrence of low CsA trough levels, this regimen appeared to be effective in preventing acute GVHD. Immunosuppressive prophylaxis beyond 1 year may be required to reduce late-onset chronic GVHD.
Schwinghammer
T L
TL
Pittsburgh Cancer Institute Adult Bone Marrow Transplant Unit, Montefiore University Hospital, University of Pittsburgh Medical Center, PA, USA.
Bloom
E J
EJ
Rosenfeld
C S
CS
Wilson
J W
JW
Przepiorka
D
D
Shadduck
R K
RK
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014184:Transplantation, Homologous
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine