Rationale for the use of ALG as sole immunosuppressant in allogeneic bone marrow transplantation for aplastic anemia.
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Biomedical subjects
Publications and source records attributed to P Cornu.
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A 45-year-old woman with severe idiopathic marrow failure was prepared for marrow transplantation by administration of cyclophosphamide (cy) 50 mg/kg on each of four successive days. She then received an intravenous infusion of 20 X 10(9) nucleated marrow cells from an HL-A matched and mixed lymphocyte culture (MLC) non-reactive sister. There was evidence for minimal marrow recovery in 1-2 months and a second marrow infusion was carried out 69 days after the first without additional immunosuppression. There was a continued slow recovery of peripheral blood counts with complete reconstitution of erythropoiesis, return of the white blood cell count to between 3 and 4000/mm3, with 50% granulocytes, and platelets to 60--70,000/mm3, 11 months after the initial grafting attempt. Red cell antigens and gamma globulin allotypes were of recipient type. The MLC and the indirect cell mediated lympholysis (CML) test became positive possibly indicating cellular sensitization to non HL-A antigens. This report of a patient with severe marrow failure documents autologous recovery of marrow function after receiving a large dose of cy and allogeneic marrow. The implications of this are discussed.
Thrombocytopenic patients who have become refractory to platelet transfusions from random donors will usually respond to HL-A compatible platelets with normal increments and hemostatic improvement. In our experience with unrelated HL-A typed donors, HL-A identity is unnecessary. Donors without excess antigen are compatible and even many donors with 1 excess antigen can be used, at any rate in immunosuppressed patients. Thus successful substitution of platelet becomes possible in refractory patients when family donors cannot be used.
A report is presented on 13 clinical bone marrow transplantations (BMT). Six of 6 patients with refractory aplastic anemia are presently alive with partial to complete hemopoetic reconstitution now lasting up to 3 years and more. It is shown that after immunosuppression with ALG and cyclophosphamide, followed by BMT, the patient's own hemopoetic system can recover. Two failures occurred in patients over 50 years of age and in one who had donor transfusions before the graft. Two of 4 patients grafted for acute refractory leukemia are alive, one being in complete remission on day 140. One died from interstitial pneumonia and one had no take although the donor was an identical twin. This patient had been on a maintenance program which included active immunotherapy.
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The autopsy and electron microscopic findings in a pair of brothers with congenital dyserythropoietic anemia (CDA) are presented. In both patients autopsy revealed severe secondary hemochromatosis, including cirrhosis of the liver and fatal heart involvement. According to current ultrastructural criteria, a mixture of CDA type I (interchromatin bridges, wide euchromatin-cytoplasmic connections) and of type II (marginal cisternae, nuclear protrusions, multinuclearity, karyorrhexis) was found in erythroblasts of one patient. In the second patient electron microscopy of bone marrow stored in formalin for several years allowed the diagnosis of CDA with marginal cisternae in retrospect. These findings illustrate the usefulness of electron microscopy for the diagnosis of CDA in unsolved cases of chronic ineffective erythropoiesis, even from formalin fixed material. For subtyping CDA into type I and II, however, other than morphological parameters should be used for definition. In the clinical management splenectomy and a drastic phlebotomy programme have been found favourable.
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