Immunodeficiency in humans as a risk factor in the development of malignancy.
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Biomedical subjects
Publications and source records attributed to J Kersey.
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Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cytotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written.
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The presence of extra reactions in the HLA typing of a combined immunodeficiency patient may be attributed to B-cell alloantibodies in the HLA typing sera. The presence of these reactions can be used to identify HLA sera containing B-cell antibodies for further B-cell studies. The alloantibodies in this study have some association with the HLA-D determinants and segregate with HLA in normal families.
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Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5-6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."
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Lymphoblasts from children with acute lymphoblastic leukemia (ALL) or malignant lymphoblastic lymphoma were studied using surface markers characteristic of T and B lymphocytes. A B-cell marker, i.e. surface immunoglobulin, was absent in all cases studied. Fouteen of 22 children (64%) had lymphoblasts with one or both markers of T lymphocytes, i.e. receptors for sheep erythrocytes (E) and/or human T-lymphocyte antigen (HTLA) detectable using heterologous antithymocyte sera absorbed with B lymphocytes. In all instances, lymphoblasts which carried E receptors also carried HTLA. However, lymphoblasts in 6 cases carried HTLA but not E receptors. It is possible that ALL may often involve T lymphocytes which are early in differentiation (i.e. prior to development of E receptors) or, alternatively, that E receptors may be lost from T cells following malignant transformation. Thymus enlargement was found only in cases of ALL or lymphoma where T markers were present. Lymphoblasts carried the same markers when examined in various sites and at various times from the same patient.
A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant.
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We performed a prospective study of infections following bone marrow transplantation in 50 patients treated for aplastic anemia or hematologic malignancy. Early, continuous prophylaxis with trimethoprim/sulfamethoxazole and oral nystatin, and empiric intravenous antimicrobial therapy during febrile granulocytopenic episodes were standard treatment for all patients. The use of trimethoprim/sulfamethoxazole did not appear to adversely affect donor marrow engraftment. Serious gram-negative bacillary and systemic Candida infections were uncommon. Although gram-positive bacterial infections were frequent, they were rarely associated with mortality. Aspergillosis emerged as the single most important infection, contributing to the death of nine patients. Cytomegalovirus diseases developed in 13 patients, seven of whom died. Patient age and chronic myelogenous leukemia were risk factors for the development of fatal infections. This study demonstrates that although certain serious infections can be controlled, there is a critical need for effective measures to prevent and treat aspergillosis and cytomegalovirus disease in these seriously compromised hosts.
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