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Biomedical subjects

A H Filipovich

Publications and source records attributed to A H Filipovich.

At least 73 records · Page 4Linked to original sources
PubMed1985

The accelerated phase of Chediak-Higashi syndrome. An expression of the virus-associated hemophagocytic syndrome?

The clinical and pathologic findings of four patients with Chediak-Higashi syndrome in the accelerated phase were studied in order to clarify the nature of this enigmatic process. Fever, lymphadenopathy, hepatosplenomegaly, and cytopenias were present in every patient. All cases demonstrated extensive parenchymal infiltrates in many organs composed of benign-appearing histiocytes manifesting hemophagocytosis accompanied by lymphocytes and plasma cells. Studies in one patient suggested a viral etiology with the findings of a low blood lymphocyte OKT4 to OKT8 ratio, acquired loss of lymphocyte response to mitogens, the presence of Epstein-Barr virus genome in the mononuclear cells of lymph node, blood, and bone marrow, and possible clinical responses to acyclovir. It is concluded that the accelerated phase of Chediak-Higashi syndrome may be the clinicopathologic expression of the virus-associated hemophagocytic syndrome.

Antibodies, Viral↗
PubMed1985

Surgery of the immunodeficient child.

A great deal has been learned about the surgery of immunodeficient patients. If one assesses the problem and follows the surgical principles described, in most instances one can solve the problem and be a great help to the oncologist and immunotherapist. A team approach is most important.

Abdomen↗
PubMed1985

Allogeneic bone marrow transplantation with related donors other than HLA MLC-matched siblings, and the use of antithymocyte globulin, prednisone, and methotrexate for prophylaxis of graft-versus-host disease.

Fifteen patients ranging in age from 1-29 years (median age 9 years) had bone marrow transplantations (BMT) from related donors other than HLA mixed lymphocyte culture (MLC) identical siblings. Donors were selected on the basis of HLA similarity and low reactivity in the MLC. Posttransplant immunosuppression consisting of methotrexate (MTX), antithymocyte globulin (ATG), and prednisone was used in an effort to decrease graft-versus-host disease (GVHD). Seven children were treated for aplastic anemia, 7 for hematologic malignancy, and 1 for osteopetrosis. Primary engraftment failure contributed to death in 3 patients, all of whom had aplastic anemia. Nine of 12 engrafted patients developed moderate-to-severe acute graft-versus-host disease. Of the 15 patients, 7 developed interstitial pneumonitis. Three patients demonstrated mixed chimerism (at or beyond 3 months posttransplant). Two of the seven patients treated for aplastic anemia are currently alive six months and more than five years posttransplant; the latter patient has chronic GVHD. Four of the seven patients treated for hematologic malignancy are currently alive more than 500 days posttransplantation. Three have chronic GVHD. Analysis of patient outcome according to the degree of similarity in histocompatibility testing revealed that patients with low reactivity in the MLC (less than 5% relative response in both directions) had a better prognosis (5/6, 83% long-term survival) than patients with maximum donor vs. recipient mixed lymphocyte culture relative response greater than 5% (1/9, 12% long-term survival), P = .016.

Adolescent↗
PubMed1985

Pretransplant conditioning with busulfan (Myleran) and cyclophosphamide for nonmalignant diseases. Assessment of engraftment following histocompatible allogeneic bone marrow transplantation.

Four pediatric patients with diseases potentially curable by bone marrow transplantation (BMT)--i.e., common variable immune deficiency, Wiskott-Aldrich Syndrome (WAS), mucopolysaccharidosis type VI, and mucopolysaccharidosis type I received a conditioning regimen consisting of busulfan and cyclophosphamide prior to BMT from HLA-identical, mixed leukocyte culture (MLC)-unreactive siblings. Only one of the four patients achieved full engraftment. Of the remaining three patients, one experienced failure of engraftment, and two had persistent mixed chimerism. Although no serious complications were directly related to the preparative therapy, the doses of busulfan and cyclophosphamide previously described to be adequate for conditioning children with WAS were completely effective in only one of three pediatric patients in this series. Despite a higher dose of busulfan (16 mg/kg), mixed chimerism was observed in a subsequent patient. Of 13 evaluable patients in the literature in whom busulfan and cyclophosphamide had been used as preconditioning regimens for a variety of nonmalignant conditions, eight demonstrated lack of complete and sustained engraftment. On the other hand, clinical improvement has accompanied partial engraftment in some cases. We conclude that additional immunosuppressive and/or myeloablative conditioning is necessary if complete engraftment is attempted in histocompatible allogeneic BMT for many of the nonmalignant disorders.

Adolescent↗
PubMed1985

Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation.

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.

Adolescent↗
PubMed1985

Restriction fragment length polymorphisms as markers of engraftment in allogeneic marrow transplantation.

We have used DNA hybridization techniques employing restriction fragment length polymorphisms (RFLPs) to quantitate the level of donor cell engraftment in bone marrow transplantation recipients. The genetic origin of the bone marrow cells and various peripheral blood populations was analyzed in 14 patients. We found at least one informative polymorphism for each donor-recipient pair. Additional markers of engraftment included cytogenetic analysis, HLA typing, and red cell typing. By DNA analysis, four patients had complete engraftment, five had partial engraftment, and five had no evidence of donor cell engraftment. In three cases, DNA analysis permitted detection of minor populations (5% to 10%) of donor or host cells. Eight of fourteen patients were evaluable for chimerism posttransplant by cytogenetic analysis. In five cases, cytogenetic results were completely concordant with DNA analyses. In two cases of apparent autologous recovery, as assessed using RFLPs, a small number of cells of donor karyotype was seen. In one other case, a small number of cells of host karyotype was not detected by RFLP studies. HLA typing in three partially engrafted patients was purely either of donor or host type. Red cell typing was discordant with DNA and/or cytogenetic results in four of eight cases. We conclude that DNA analysis at a limited number of informative genetic loci is useful for quantitating the degree of engraftment in multiple populations of nondividing cells following allogeneic bone marrow transplantation.

Adolescent↗
PubMed1985

Comparison of three techniques for the ex vivo elimination of T cells from human bone marrow.

The high incidence of graft-vs-host disease (GVHD) in allogeneic bone marrow transplantation (BMT) is a significant cause of morbidity and mortality, despite pharmacological prophylactic regimes. Laboratory technologies have been developed to eliminate the immunocompetent T-lymphocyte, the proposed effector cell in the GVHD reaction. In this study, three techniques for the ex vivo purging of T cells from human bone marrow (BM) were compared. BM treatment groups consisted of T-cell depletion by the monoclonal antibodies OKT3 and OKT11A plus complement (MoAb + C), soybean agglutination followed by sheep erythrocyte rosette depletion, or triple rosetting with neuraminidase-treated sheep erythrocytes. Mean final cell yields were 37.2 +/- 4.0%, 2.8 +/- 0.8%, and 2.5 +/- 1.3%, respectively, while final yields of BM progenitor cells, assayed in the double-layer soft-agar CFU-c assay, were 28.5 +/- 6.5%, 3.9 +/- 2.1%, and 10.5 +/- 3.8%, respectively. The three techniques were comparably efficient in elimination of mitogenic responses to irradiated allogeneic lymphoblastoid cells and cytotoxic lymphocyte responses of the BM. Immunofluorescence after T-cell depletion showed greater than 97.5% of all OKT3-positive cells to be eliminated by each technique. Despite the fact that all three techniques were effective in T-cell depletion, treatment with anti-T-cell MoAbs + C proved less labor-intensive and resulted in higher cell yields.

Antibodies, Monoclonal↗
PubMed1985

Comparison of two immuno-mechanical methods of T-cell depletion of human bone-marrow for prevention of graft-versus-host disease: soybean lectin agglutination and sheep erythrocyte rosette depletion versus triple rosette depletion.

Depletion of T-lymphocytes from HLA-mismatched donor bone marrow can be accomplished by either triple neuraminidase-treated sheep erythrocyte depletion (3En) or soybean agglutination and sheep erythrocyte depletion (SBA/E/En). T-lymphocyte depletion by 3En resulted in higher yields of all marrow precursor phenotypes (studied by a battery of monoclonal antibodies) than did SBA/E/En depletion. While both procedures enriched for some early precursor cells (e.g., HLA-DR and/or terminal deoxynucleotidyl transferase (TdT) positive cells), greater numbers of these cells were available after 3En. Clinical benefits which may be derived from the larger inoculum of T-depleted bone-marrow cells available after 3En treatment remain to be studied.

Animals↗
PubMed1984

Ex-vivo treatment of donor bone marrow with anti-T-cell immunotoxins for prevention of graft-versus-host disease.

Two patients undergoing marrow transplantation for acute lymphocytic leukaemia in third remission received from histocompatible siblings marrow pretreated with a mixture of three anti-T-cell immunotoxins, consisting of murine monoclonal antibodies covalently linked to ricin. This marrow processing effectively eliminated functional T-cell responses while preserving the marrow precursors necessary for sustained haematoimmunopoietic engraftment. No post-transplant immunoprophylaxis was administered. Both patients showed prompt peripheral engraftment and were discharged from hospital within a month of transplantation. No toxic effects or graft-versus-host disease were apparent after the administration of immunotoxin-treated marrow. Ex-vivo immunotoxin pretreatment appears a safe and simple procedure which deserves further clinical testing as a sole method of graft-versus-host disease prophylaxis.

Adolescent↗
PubMed1984

Familial alopecia areata. HLA antigens and autoantibody formation in an American family.

Ten members of a white American family, spanning three generations, were studied. Three family members from two different generations were affected with hair loss. Two had alopecia universalis; one had alopecia areata. All subjects were HLA-typed using 131 antiserum samples obtained from multiparous female donors defining 41 HLA-A and HLA-B antigen specificities. Six haplotypes were identified. The affected persons and four other family members shared a common haplotype, HLA-A2,B40. The OKT4 (helper), OKT8 (suppressor-cytotoxic) cells, OKT4-OKT8 (helper-suppressor-cytotoxic) ratios and the percentage of B cells found were comparable for both the 12 control subjects and the family members studied. However, family members showed increased autoantibody formation, decreased T-cell percentages, and concanavalin A-induced suppression of the normal lymphocyte response to mitogens.

Adolescent↗
PubMed1984

Epidermodysplasia verruciformis in a setting of common variable immunodeficiency.

A 14-year-old native American female with common variable immunodeficiency was admitted for bone marrow transplantation. Preoperative evaluation showed a generalized lichenoid papular eruption present for several years. Light microscopy revealed expansion of the epidermis by atypical keratinocytes; electron microscopy showed intranuclear papillomavirus inclusions within the granular keratinocytes; DNA hybridization revealed a type 5-related human papilloma virus homology. Four days after bone marrow transplantation the lichenoid papules blackened and began to disappear. Within 30 days after bone marrow transplantation the distribution and appearance of the papules was similar to that of the pretransplantation evaluation. One year after transplantation the patient showed evidence of a successful T lymphocyte graft. No transformation to squamous cell carcinoma had occurred. Epidermodysplasia verruciformis has been associated with deficient cell-mediated immunity, the varying severity of which does not predict the tendency to neoplasm formation (2, 5). Several distinct human papillomavirus genomes have been recovered with DNA hybridization techniques in these patients. It is hoped that the bone marrow transplantation might be associated with diminished transformation to squamous cell carcinoma.

Adolescent↗
PubMed1984

Suppressor cell number and function in alopecia areata.

Several values of immunologic function were studied and correlated with disease activity and extent in 14 patients with alopecia areata, alopecia totalis, or alopecia universalis and in a concurrently studied age- and sex-matched control group. As compared with the control group, the patients showed a significantly increased incidence of autoantibody formation, increased concanavalin A-induced suppression of the normal lymphocyte response to mitogens, an increased proportion of suppressor-cytotoxic cells in the peripheral blood, and a decrease in the absolute B-cell count. Absolute total T-cell counts, quantitative serum immunoglobulin determinations, and lymphocyte proliferation after exposure to the mitogens--concanavalin A, phytohemagglutinin, and pokeweed--and to tetanus antigen were comparable for both groups. Neither the percentage of concanavalin A-induced suppression of the normal lymphocyte response to mitogens nor the helper-suppressor ratio correlated significantly with the extent of hair loss. However, patients, particularly those who demonstrated spontaneous regrowth of hair, had increased concanavalin A-induced suppression in conjunction with an increase in the proportion of peripheral suppressor cells.

Adolescent↗
PubMed1983

Biphenotypic leukemia: immunologic and morphologic evidence for a common lymphoid-myeloid progenitor in humans.

A 5-year-old white girl had a white blood cell count of 80,000/cu mm and 82% lymphoblasts in the peripheral blood. Acute lymphocytic leukemia (ALL) was diagnosed, defined by typical morphology (FAB-L1), a positive reaction for terminal deoxynucleotidyl transferase (TdT) and characteristic surface antigens detected with lymphoid monoclonal antibodies. The patient's peripheral lymphoblast count fell rapidly with ALL therapy, but the WBC count began to rise unexpectedly on the sixth day of treatment, with 84% myeloblasts and monocytoid blasts. Malignant cells in the bone marrow showed FAB-M4 morphology and were no longer reactive with antibodies directed against TdT or common ALL antigen. However, the myeloblasts continued to react with some of the same monoclonal antibodies as the original leukemia cells, and in addition expressed new determinants detected by monoclonal antibody TA-1 and peanut agglutinin. The rapid dynamic evolution of the malignancy during the course of induction chemotherapy favors the existence of a stem cell capable of differentiation into both lymphoid and myeloid clones that are both independently and selectively sensitive to specific chemotherapeutic regimens.

Antibodies, Monoclonal↗