Abstract
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.
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- Donatsch P., Abisch E., Homberger M., Traber R., Trapp M., Voges R. A radioimmunoassay to measure cyclosporin A in plasma and serum samples. J Immunoassay. 1981;2(1):19–32. doi: 10.1080/01971528108062989. [DOI] [PubMed] [Google Scholar]
- Gluckman E., Devergie A., Lokiec F., Poirier O., Baumelou A. Nephrotoxicity of cyclosporin A in bone-marrow transplantation. Lancet. 1981 Jul 18;2(8238):144–145. doi: 10.1016/s0140-6736(81)90320-2. [DOI] [PubMed] [Google Scholar]
- Granger S., Janossy G., Francis G., Blacklock H., Poulter L. W., Hoffbrand A. V. Elimination of T-lymphocytes from human bone marrow with monoclonal T-antibodies and cytolytic complement. Br J Haematol. 1982 Feb;50(2):367–374. doi: 10.1111/j.1365-2141.1982.tb01928.x. [DOI] [PubMed] [Google Scholar]
- Hows J. M., Palmer S., Want S., Dearden C., Gordon-Smith E. C. Serum levels of cyclosporin A and nephrotoxicity in bone marrow transplant patients. Lancet. 1981 Jul 18;2(8238):145–146. doi: 10.1016/s0140-6736(81)90321-4. [DOI] [PubMed] [Google Scholar]
- Hows J., Harris R., Palmer S., Gordon-Smith E. C. Immunosuppression with cyclosporin A in allogeneic bone marrow transplantation for severe aplastic anaemia: preliminary studies. Br J Haematol. 1981 Jun;48(2):227–236. doi: 10.1111/j.1365-2141.1981.tb08456.x. [DOI] [PubMed] [Google Scholar]
- Kendra J., Barrett A. J., Lucas C., Joshi R., Joss V., Desai M., Halil O., Rogers T. R., Hobbs J. R., Hugh-Jones K. Response of graft versus host disease to high doses of methyl prednisolone. Clin Lab Haematol. 1981;3(1):19–26. doi: 10.1111/j.1365-2257.1981.tb01305.x. [DOI] [PubMed] [Google Scholar]
- Lerner K. G., Kao G. F., Storb R., Buckner C. D., Clift R. A., Thomas E. D. Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc. 1974 Dec;6(4):367–371. [PubMed] [Google Scholar]
- Palacios R., Möller G. Cyclosporin A blocks receptors for HLA-DR antigens on T cells. Nature. 1981 Apr 30;290(5809):792–794. doi: 10.1038/290792a0. [DOI] [PubMed] [Google Scholar]
- Powles R. L., Barrett A. J., Clink H., Kay H. E., Sloane J., McElwain T. J. Cyclosporin A for the treatment of graft-versus-host disease in man. Lancet. 1978 Dec 23;2(8104-5):1327–1331. doi: 10.1016/s0140-6736(78)91971-2. [DOI] [PubMed] [Google Scholar]
- Powles R. L., Clink H. M., Spence D., Morgenstern G., Watson J. G., Selby P. J., Woods M., Barrett A., Jameson B., Sloane J. Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation. Lancet. 1980 Feb 16;1(8164):327–329. doi: 10.1016/s0140-6736(80)90881-8. [DOI] [PubMed] [Google Scholar]
- Reisner Y., Kapoor N., Kirkpatrick D., Pollack M. S., Dupont B., Good R. A., O'Reilly R. J. Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells. Lancet. 1981 Aug 15;2(8242):327–331. doi: 10.1016/s0140-6736(81)90647-4. [DOI] [PubMed] [Google Scholar]
- Saurat J. H., Gluckman E., Bussel A., Didierjean L., Puissant A. The lichen planus-like eruption after bone marrow transplantation. Br J Dermatol. 1975 Dec;93(6):675–681. doi: 10.1111/j.1365-2133.1975.tb05118.x. [DOI] [PubMed] [Google Scholar]