A patient suffering from acute lymphoblastic leukemia in the third progressive phase, refractory to the majority of available treatments, was given total-body irradiation of 800 r. dosage, after administration of methyl-nitro-imidazolyl-mercaptopurine (300 mg. daily for 4 days). One week after irradiation, he received an infusion of a mixture of equal parts of bone marrow from six donors (mother, sister, father and three brothers), a total of 5.8 x 1010 nucleated cells.
Myeloid restoration began 2 weeks after the infusion and continued to progress rapidly. The reality of the graft was demonstrated by study of the erythrocytic antigens. Nearly all the erythrocytes found in the blood after 6 months belonged to the phenotype of one of the male donors.
Studies of chromosomes and leukocyte sex chromatin suggested that a small proportion of leukocytes were being produced by the cells of one of the female donors. The patient was found to produce beta 2A, beta 2M and gamma globulins of the Inv type of the donors, suggesting that lymphoid cells may also have been successfully grafted.
A skin graft from the male donor whose marrow graft had apparently been accepted was still perfectly intact 7 months after grafting, whereas the grafts from other donors were rejected, indicating a specific tolerance to tissues from this donor. Previous studies of compatibility between the recipient and the various donors by a histocompatibility test described by us, or by means of similarities in leukocyte antigens, indicated that the accepted donor had been antigenically more nearly compatible than the others.
What appeared to be a secondary syndrome became manifest 1 week after marrow transfusion; it consisted of weight loss, digestive disorders (anorexia, nausea, vomiting, diarrhea), hepatic disturbances (hepatomegaly, increased serum concentrations of various enzymes), transient polyadenopathy (histologically composed of histiocytic proliferation and lymphocytic aplasia), desquamative erythrodermia, eosinophilia exceeding 50 per cent, and superinfection (including a probable miliary tuberculosis). The syndrome was controlled by careful symptomatic treatment; its intensity gradually abated.
Reactivation of the secondary syndrome was accomplished by reinjection of leukocytes from the donor whose graft had been tolerated. This was controlled by Δ-1-cortisone and symptomatic treatment.
The patient was still alive and in apparently complete hematologic remission from the leukemia 12 months after the treatment described above. Particular reasons for this success possibly include the absence of previous blood transfusions and the use of multiple marrow donors.
MEDIBCRAITIOA volunteers, and a British strain in doses ranging from 10' to 106 EID.0 to 30 volunteers. One month later 75 of the vaccinated volunteers were given 104 EID50 of the British vaccine. In addition, 55 volunteers with neutralizing antibody were given 107 EID50 of the Iksha vaccine by drops or spray, and 53 volunteers were given the same dose of vaccine inactivated with formalin.Of the volunteers without antibody 41% had mild respiratory symptoms after the first dose, and 8% after the challenging dose; 9 % of the volunteers with antibody who were given live vaccine had similar symptoms.Virus was recovered from 25% of the volunteers without antibody after the first dose of vaccine, and from 5 % after the challenging dose. Immediately before the challenging dose of vaccine 21% of the volunteers showed fourfold or greater haemagglutination-inhibition antibody response and 21 % a complement-fixation response; two weeks after the challenging dose the proportions were 29% and 19%, respectively.A much higher proportion of volunteers showed an antibody response after live than after inactivated vaccine.A dose of 10' EID50 of the British vaccine gave similar results to that of 106 or 107 EID50 of the Iksha vaccine.
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