Biomedical subjects
Publications and source records attributed to E C Saltzstein.
Breast carcinoma occurred in a 25-year-old man. This is to our knowledge, the seventh reported instance of this extremely rare cancer. Despite its infrequent occurrence, high cure rates can be obtained if it is detected and treated early. Breast masses in young men must not be ignored.
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Transplantation into lethally irradiated mice of hematopoietic and lymphoid cells from immature donors which hypothetically will not mount a cell mediated attack against simultaneously inoculated human tumor cells has resulted in tumor engraftment and growth in long-term surviving radiation chimeras. Twenty-four hours after lethal irradiation, A or CBA mice were given iv injections of 2 X 10(7) fetal liver cells from syngeneic donors of 14, 16, or 18 days of embryonation and sc injections of 1, 3, or 6 X 10(6) human choriocarcinoma (C-1, C-2, and C-3) cells or human breast carcinoma (B-1) cells that had been maintained in culture. Palpable tumors greater than or equal to 5 mm were noted in 18/22 mice injected with C-1, 9/16 with C-2, 10/10 with C-3, and 18/30 with B-1. Tumors of 17 (31%) of mice remained palpable until death of the animal or until termination of the experiment 100 days post inoculation. Histologic study of autopsy specimens revealed malignant tumors with occasional pulmonary metastases. Human chorionic gonadotropin was found in the serum of mice that received choriocarcinoma cells.
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CBA mice were exposed to a supralethal dose of whole body X-irradiation and recieved transplants of graded, small doses of bone marrow, fetal liver, or fetal liver plus fetal thymus cells obtained from H-2 matched C58 or H-2 mismatched A donors. Survival at 20 days was used to evaluate the ability of the transplants to restore hematopoiesis following the acute radiation injury. In the higher dose ranges of 6 X 10(7) and 1.2 X 10(8) cells/kg body weight, the fetal cells were as effective as adult bone marrow in both the matched and mismatched strain combinations. Survival at 100 days was used to evaluate the severity of chronic graft-versus-host disease produced by each of the transplants. In the higher dose ranges, cells from fetal donors promoted higher long-term survival rates than did comparable doses of bone marrow cells in both the matched and mismatched strain combinations. In some experimental groups, the addition of fetal thymus cells to fetal liver cells resulted in higher short-term and long-term survival rates than did fetal liver alone, but this was inconsistent and generally fell short of statistical significance. The most important finding was that cells from mismatched unrelated fetal donors (using a cell dose per kilogram body weight comparable to the number of fetal liver and thymus cells which would be obtainable from one human fetus at 14 weeks of embryonation) promoted higher long-term survival rates than did bone marrow transplants from matched unrelated donors.
Adoptive immunotherapy in the form of a transient graft of mismatched DBA/2 BM + LN cells was used in combination with several chemoradiotherapy regimens to treat AKR mice bearing advanced SLL. Leukemic mice treated in this manner had a significant prolongation of their MST and significantly higher survival rates 60 and 90 days posttreatment than corresponding control groups. Syngeneic- or allogeneic-matched cells did not provide substantial GVL effect. An inverse relationship that influenced survival was observed between the radiation dose and the dose of GVL effector cells used to treat leukemic AKR mice in the treatment model. Recurrence leukemia remains a major problem.
Groups of AKR mice bearing spontaneous leukemia-lymphoma were treated with five different combinations of chemotherapy or chemoradiotherapy. Each treatment combination was given in two sequences--high dose first and low dose last, or low dose first and high dose last--administered over 6-7 days. When the initial treatment was a high dose of chemotherapy, radiotherapy, or chemoradiotherapy, mortality in the first 24 hours exceeded 40%, and at least 70% of the mice in each group were dead within 2 weeks. When low-dose chemotherapy was given first, mortality in the first 24 hours was minimal but, most significantly, no deaths occurred in the 24 hours after subsequent high-dose treatment. In the most successful group (100 mg cyclophosphamide/kg on day 0, and 250 mg cyclophosphamide/kg and 400 R total-body X-irradiation on day 7), the median survival time increased significantly as compared with the median survival time among mice given the same regimen in reverse sequence (p less than 0.001) or among untreated control mice (p less than 0.01). With this regimen, survival 60 days after the last treatment was 47%. No mouse survived 30 days when the sequence of treatments was reversed. From these results, we conclude that chemotherapeutic and chemoradiotherapeutic regimens for AKR spontaneous leukemia-lymphoma should be designed so that low, minimally lethal doses precede higher doses.
A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To "rescue" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice.
A report of a patient treated by partial resection of the ureter and renal autotransplantation for recurrent benign ureteral tumors and impaired renal function in the contralateral kidney is presented. Autotransplantation of the ipsilateral kidney associated with benign disease of the renal excretory system is recommended even with normal function of the contralateral kidney. Experience with renal homotransplantation has led to excellent technical and functional results from autotransplantation, and use of the procedure is expanding to include treatment of a variety of renal, ureteral, and renovascular pathology. The role of renal autotransplantation in the preservation of functioning renal units is emphasized.
Lethally irradiated CBA (H-2k) mice were treated with small numbers of liver cells from strain-A (H-2a) fetal donors. Recovery from the radiation injury was dependent upon the dose of liver cells administered. Giving very small numbers of fetal thymus cells, in addition to liver cells, had a highly significant and salutary effect on survival. The results suggest that clinical transplantation of liver cells from a single fetus might succeed if thymus cells are added.
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Quantification of the antileukemic reactivity of transplanted immunocompetent cells from various allogeneic donors was achieved against a long-passage lymphocytic leukemia of AKR mice. Adoptive immunotherapy was the exclusive antileukemic treatment. Cells from DBA/2 donors exhibited maximal antileukemic effect, inactivating up to an estimated 10(7) leukemia cells. The cellular events were interpreted by using a theoretical cytokinetic construct.
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