Oral
cyclosporin A was used as prophylaxis against
graft-versus-host disease in (a) 31 patients with acute leukaemia or
aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with
inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the
cyclosporin A, 31 patients (86%) suffered an acute form of
graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with
immunosuppressive agents and caused the death of only one patient.
Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "
capillary leak" syndrome, fatal in two patients. In children
hypertension, fits, and fluid retention were common side effects. Blood concentrations of
cyclosporin A correlated with blood
urea values and blood pressure but did not predict the occurrence of
graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral
cyclosporin A is extremely effective at reducing the severity of
graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.