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Biomedical subjects

A H Filipovich

Publications and source records attributed to A H Filipovich.

82 records · Page 5Linked to original sources

Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone-marrow transplantation.

Ten consecutive patients undergoing transplantation of bone marrow from histocompatible siblings for treatment of haematological malignancy took part in a pilot study to test the safety of in-vitro treatment of donor bone marrow with monoclonal antibody OKT3. Three male and seven female patients aged 7-34 years received concentrated bone marrow buffy-coat cells which had been incubated with OKT3 before infusion. In-vitro studies confirmed that almost all immunocompetent T lymphocytes in the bone-marrow samples were coated with OKT3 at the time of infusion. In vitro, neonatal rabbit complement inhibited the proliferation of bone-marrow T lymphocytes in samples preincubated with OKT3 to less than 4% of the mitogenic responses of the untreated bone marrow. In contrast, fresh autologous complement did not effectively lyse OKT3-treated bone-marrow cells. Infusion of OKT3-treated bone marrow was safely accomplished, and engraftment was achieved in all patients (mean 23 days). Nine of ten patients survived for more than 100 days after bone-marrow transplantation, but significant acute graft-versus-host disease (GvHD) requiring treatment with steroids developed in five of the ten. This finding suggests that further modifications for bone-marrow pretreatment will be needed to achieve effective prophylaxis against acute GvHD in histocompatible bone-marrow transplantation.

Acute Disease↗

Treatment of donor bone marrow with OKT3 (PAN-T monoclonal antibody) for prophylaxis of graft-vs.-host disease (GvHD) in histocompatible allogeneic bone marrow transplantation (BMT): a pilot study.

Ten consecutive patients ranging in age from seven to 34 years undergoing bone marrow transplantation from histocompatible siblings for treatment of hematologic malignancy were entered into a pilot study designed to test the safety of OKT3 pretreatment of donor bone marrow for prevention of graft-vs.-host disease. Concentrated donor bone marrow specimens containing a mean of 6.5 X 10(8) nucleated cells/kg recipient weight were treated with 1 mg of OKT3 at 4 degrees C for 30 min prior to administration to the recipient. In vitro immunofluorescent studies confirmed that all OKT3+ cells in bone marrow had effectively bound antibody. Furthermore the addition of neonatal rabbit complement in vitro decreased the proliferative responses of donor bone marrow cells to phytohemagglutinin and concanavalin A (Con A) to less than or equal to 4% of untreated bone marrow. No significant complications resulted from the administration of OKT3 and all recipients engrafted after a mean duration of 22 days. Nine of the 10 patients survived for more than 100 days after marrow transplantation. However, five of the 10 patients developed acute graft-vs.-host disease and required steroid therapy. While this pilot study suggests that OKT3 can be used safely in the bone marrow transplantation setting, further modification of our OKT3 treatment procedure will be necessary to completely eradicate graft-vs.-host disease in histocompatible bone marrow transplantation.

Acute Disease↗

'Pseudolymphoma'. A case associated with primary immunodeficiency disease and polyglandular failure syndrome.

An atypical lymphoproliferative process occurred in the liver and spleen of a child with combined immunodeficiency disease and polyglandular failure syndrome. The initial pathologic interpretation was that of malignant lymphoma, although the child's subsequent clinical course was complicated by rheumatoid arthritis, thyroiditis, and chronic active hepatitis, with no clear evidence of lymphoid neoplasia. This case illustrates that unusual lymphoid proliferations in patients with immunodeficiencies may simulate malignant lymphoma.

Adolescent↗

ATG plus corticosteroid therapy for acute graft-versus-host disease: predictors of response and survival.

Innovative treatment strategies for acute graft-versus-host disease (aGVHD) have not replaced corticosteroids as the primary therapy. We retrospectively reviewed 74 patients who received equine antithymocyte globulin (ATG) in addition to corticosteroids as therapy for GVHD, 21 who received primary therapy and 53 who received ATG after progressing or failing to improve with corticosteroids alone. The groups were comparable in clinical characteristics and in timing and severity of GVHD. After primary therapy with ATG 67% of patients' GVHD symptoms were stable or improved by 28 days versus 56% in those receiving secondary ATG (p = 0.57). In univariate analysis the absence of multiple organ, GI, and liver aGVHD and a clinical stage score < or = 4 were predictive of a favorable response, while in a multivariate logistic regression model only a clinical stage score < or = 4 was independently associated with a favorable response (odds ratio 0.08, 95% CI 0.02-0.32, p = 0.003). ATG response rates and 6-month survival (38 vs. 40%, p = 0.89) were similar following primary and secondary ATG. Patients stable or improved 28 days after ATG therapy had a significantly better 6-month survival than those whose aGVHD had progressed (50 vs. 30%, p = 0.02). Further study is required to assess whether some initial presentations of aGVHD would predictably fail corticosteroid therapy and may thus suggest a role for ATG in the primary management of aGVHD. For this determination, formal prospective comparative trials are needed.

Adrenal Cortex Hormones↗

Immunodeficiency-disease-associated atypical chronic hepatitis: a clinicopathologic study.

Chronic hepatitis occurring in patients with primary immunodeficiency disease is an uncommonly reported phenomenon. This study describes our experience with 3 patients with various immunologic abnormalities who developed chronic atypical lymphocytic infiltrates in the liver. There was a temporal relationship to Epstein-Barr virus infection in 2 cases and hepatitis A in 1. In view of the increased incidence of malignant lymphoma in several of the primary immunodeficiency states, these cases present a difficult diagnostic challenge. The recognition of the association of infiltration of the liver with small cleaved lymphocytes and a viral infection in an immunodeficient patient should alert the pathologist to the possibility that the infiltrate does not represent malignant lymphoma. These cases may be analogous to similar virus-associated lymphoproliferative disorders described in the acquired immunodeficiency of renal transplantation.

Adolescent↗