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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 721 records · Page 40Linked to original sources

Pathology of acute graft-versus-host disease in the dog. An autopsy study of ninety-five dogs.

The morphology of graft-versus-host disease (GVHD) in canine radiation chimeras was studied by examination of autopsy tissue from 95 dogs including: 1) 13 healthy, untreated dogs; 2) 9 dogs given 1200 R total body irradiation and no marrow infusion; 3) 17 dogs given 1200 R and autologous marrow infusion; 4) 25 dogs given 1200 R and hemopoietic cells from dog-leukocyte-antigen (DLA)--identical littermates; and 5) 31 dogs given 1200 R and nonidentical DLA hemopoietic cells. Some of the dogs in Groups 3--5 received a postgrafting methotrexate (MTX) regimen of 0.25--0.5 mg/kg body weight on Days 1, 3, 6, and 11 and once weekly until Day 102. Prominent lesions were found in the small and large intestines, skin, and liver of dogs with allogeneic grafts. Skin lesions consisted of lymphocytic infiltrates of epidermis with necrosis of basal epidermal cells progressing to denudation. Gut lesions consisted of mucosal destruction progressing from crypt abscess formation to denudation. Liver lesions consisted of portal triaditis, plasmacytic and lymphocytic infiltrates, necorsis and atypia of small bile ducts, and scattered individual hepatocyte necrosis. These lesions were differentiated from changes caused by irradiation and MTX and were deemed characteristic of GVHD. The overall severity of GVHD lesions was less in the identical DLA group than in the nonidentical DLA group, and also less in dogs treated with MTX than in those not given MTX. The degree of lymphoid depletion in the lymph nodes, spleen, and intestinal lymphoid tissue was very similar in dogs with autologous and allogeneic grafts at comparable survival times. No specific evidence of pancreatic or renal involvement in GVHD was discovered.

Animals↗

Nonspecific suppressor cells in patients with chronic graft-vs-host disease after marrow grafting.

Forty-four human long-term survivors after marrow transplantation for aplastic anemia or hematologic malignancy were studied for the presence of circulating nonspecific suppressor cells. Twenty-two of the patients were healthy and 22 had mild to moderately severe chronic graft-vs-host disease (GVHD). Patient mononuclear cells (of donor origin) were tested for their ability to suppress the responses of lymphocytes obtained from the respective marrow donors to alloantigens in mixed leukocyte culture (MLC) and/or to concanavalin A (Con A). Tests were carried out between 199 and 2393 (median 376) days after transplantation. Cells from only 1 of 22 patients without chronic GVHD showed suppression of donor cell blastogeneis responses. In contrast, cells from 11 of 22 patients with chronic GVHD showed more than 30% suppression of donor cell responses in MLC and/or to Con A. The finding of suppressor cells was not related to the time of testing after grafting nor to immmunosuppressive therapy. Nonspecific suppressor activity was abrogated by irradiation with 1600 rads in vitro in five of six cases tested. Nonspecific suppressor cells may be one explanation for the severe combined immunodeficiency and the recurrent infectious complications characteristic of patients with chronic GVHD.

Bone Marrow Transplantation↗

Total body irradiation and autologous marrow transplantation as consolidation therapy for spontaneous canine lymphoma in remission.

Seventeen dogs with spontaneous generalized lymphoma in complete clinical remission induced with combination chemotherapy were given 1100 R total body irradiation (TBI) and autologous marrow grafts as consolidation therapy. Marrow was obtained immediately before TBI, stored at 4 degrees C, and infused immediately after TBI. Two dogs died because of failure to regain adequate marrow function, 8 died after developing recurrent lymphoma and 2 died of miscellaneous causes. Five dogs are alive in unmaintained complete clinical remission 200-663 days after initiation of chemotherapy. In a comparable group of 8 dogs in complete remission after combination chemotherapy but not given consolidation therapy, none remained in remission beyond 113 days. These results indicate that high dose TBI in conjunction with autologous marrow grafting results in prolonged remission duration in dogs with spontaneous lymphoma.

Animals↗

Allogeneic marrow grafting for acute leukemia: a follow-up of long-term survivors.

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years. At the time of the last report 4 of the 17 patients had relapsed: two in the marrow, one in the central nervous system and one in the testicle. Three of these four patients have died of their disease 27, 34 and 50 months following transplant. The patient with a solitary testicular relapse remains in complete remission 49 months after local irradiation without concomitant systemic therapy. One other patient died 26 months following transplantation from cardiopulmonary complications following multiple respiratory infections. Of the 13 surviving patients, three suffer from chronic graft-versus-host disease. Summaries of the problems encountered in these patients after the first 100 days are presented. Ten of the original 100 patients are living productive lives 36-80 months after transplantation. The data clearly demonstrate that long-term unmaintained remissions are possible in a small fraction of patients with terminal leukemia treated with various chemotherapy regimens and TBI followed by marrow transplantation.

Adolescent↗

Erythroid colony stimulating and inhibiting cells in peripheral blood of transfused dogs: separation of function by velocity sedimentation.

We have previously shown that the addition of normal dog peripheral blood lymphocytes (PBL) to cultures of allogeneic marrow increases the number of marrow-derived erythroid colonies (EC), but that PBL from transfused dogs usually inhibit EC growth from marrow of the transfusion donor. In this study, the cells in normal dog PBL responsible for stimulating EC growth were shown to sediment in a narrow peak at 4.30 mm/hr. A similar population of stimulating cells exists in transfused dogs and can be separated, on the basis of size, from cells that inhibit EC growth. EC-stimulating cells from transfused dog PBL sediment at 3.3--5.0 mm/hr, while cells responsible for inhibition are larger and sediment more rapidly at 5.4--8.1 mm/hr. These data demonstrate that cells capable of stimulating allogeneic EC are present in transfused dogs, but their stimulating ability is masked by the presence of EC-inhibiting cells. Thus, coculture experiments designed to test lymphocyte/marrow cell interactions may miss significant but opposing effects if unfractionated cells are used.

Animals↗