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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 541 records · Page 30Linked to original sources
PubMed1984

Marrow transplantation in hepatitis-associated aplastic anemia.

Seventeen patients who developed aplastic anemia in association with viral hepatitis were transplanted with sibling marrow. Of the 16 HLA-identical recipients, 14 were conditioned with cyclophosphamide, 200 mg/kg, and two received 10 Gy total body irradiation. One HLA-nonidentical recipient received 123 mg/kg cyclophosphamide and 10 Gy total body irradiation. Of the 14 patients conditioned with cyclophosphamide alone, one died on day 49 after graft rejection, and 13 had sustained engraftment. Six of the 13 developed acute graft-versus-host disease (GVHD), which led to death from opportunistic infections 84, 97, and 130 days after transplantation in three patients. Four of the 13 developed chronic GVHD, two without preceding acute GVHD. Currently, ten of the 14 cyclophosphamide-conditioned patients are alive 0.9-12.4 (median 5.9) years from transplantation. The two HLA-identical recipients conditioned for grafting with total body irradiation died after failure of engraftment, and one also developed concomitant hepatic venocclusive disease. The mismatched recipient conditioned with radiation and cyclophosphamide died of severe GVHD 18 days posttransplant. We conclude that survival, graft rejection, and incidence of acute and chronic GVHD after marrow transplantation for hepatitis-associated aplastic anemia are similar to those of patients transplanted for aplastic anemia of other etiologies. Previous hepatic damage from viral hepatitis and liver function abnormalities existing at the time of grafting do not appear to increase the risk of posttransplant morbidity and mortality from hepatocellular damage or venocclusive disease in cyclophosphamide-conditioned patients.

Adolescent↗
PubMed1984

Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants.

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.

Adolescent↗
PubMed1984

Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease.

Four different murine monoclonal anti-T cell antibodies were administered to 15 patients with severe steroid resistant graft versus host disease (GVHD) in a phase I clinical trial in order to evaluate feasibility and toxicity. Antibodies 9.6 (IgG2a) and 35.1 (IgG2a) bind to separate epitopes on the E receptor (Tp50); antibody 10.2 (IgG2a) binds to the murine Lyt-1 homolog (Tp67); and antibody 12.1 (IgG2a) binds to a cell surface antigen with a molecular weight of approximately 100,000 daltons (Tp100). A total of 151 infusions were given, ranging in dose from one to 20 mg, each administered over a one to four hour period. One patient received a total of 259 mg of antibody over a period of 45 days. Six infusions (4%) in two patients were associated with fever or fever and chills. By decreasing the infusion rate, subsequent infusions to these two patients were accomplished without additional reactions. Although most of the patients treated with monoclonal antibodies required platelet support, the number of platelet units given was not significantly different from similar patients not receiving monoclonal antibodies. Six of ten patients receiving intermediate to high doses (5-20 mg) antibody therapy had evidence of at least partial improvement in GVHD in at least one involved organ system. None of the patients became immunized to mouse immunoglobulin. Our results suggest that therapy of GVHD with murine monoclonal anti-T cell antibodies is feasible and that these antibodies apparently can be administered to marrow transplant patients without significant toxicity. Further studies are required to determine which antibodies or combinations of antibodies have optimal anti-GVHD effect.

Acute Disease↗
PubMed1984

Immune responses in an untransfused patient with aplastic anemia: analysis of cytolytic and proliferative T cell clones.

Unexpected unidirectional reactivity was noted in MLC by the cells of an untransfused patient with aplastic anemia against cells from her genotypically HLA identical brother. To analyze this reactivity, lymphocytes from the patient were primed in vitro for six days with irradiated lymphocytes from the HLA identical brother and then cloned by limiting dilution in the presence of interleukin-2. Following a period of clonal expansion, the patient's cells were tested for specific proliferative (PLT) and cytolytic (CTL) activity against cells of the brother. Thirty-six clones demonstrated proliferative activity, 30 clones demonstrated cytolytic activity, and 114 clones showed neither. No clone demonstrated both cytotoxic and proliferative activity. Several patterns of specificity were seen for the cytolytic T cell (CTL) clones, including both allo- and autoreactivity. Two distinct patterns of specificity were noted for the proliferative clones: one reactive to cells from DR3-positive males; the other reactive only to cells from certain DR2-positive males and females. The DR3-restricted clones are presumably directed towards the H-Y minor histocompatibility antigen while the DR2-restricted clones are directed toward an undefined minor histocompatibility antigen. It is thus possible to isolate both alloreactive and autoreactive T cells from the peripheral blood of some untransfused patients with aplastic anemia.

Anemia, Aplastic↗
PubMed1984

Cataracts after total body irradiation and marrow transplantation: a sparing effect of dose fractionation.

We examined 277 patients, who have been followed for 1 to 12 years after marrow transplantation, for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, usually cyclophosphamide 50 mg/kg X 4 intravenously, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing 60Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients), usually at increments of 2 to 2.25 Gy/day for 6 to 7 days for cumulative doses of 12 to 15.75 Gy. To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, and 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only (p less than 0.00005), suggesting a significant sparing effect with use of TBI dose fractionation. Addition significant risk factors included the chronic use of steroids posttransplant (highly associated with the presence of chronic graft-versus-host disease), and the diagnoses of acute lymphoblastic or chronic myelogenous leukemia.

Adolescent↗
PubMed1984

Monoclonal antibodies to canine cell surface antigens: a comparison of screening assays.

An ELISA for detection of monoclonal antibodies to surface antigens on canine lymphocytes was evaluated, and results were compared with three additional tests: a radioimmunoassay using 125I-labeled staphylococcal protein A (IPA), the fluorescence activated cell sorter (FACS II), and CdL. Three potentially interesting hybridomas were subsequently selected from two fusions.

Animals↗
PubMed1984

Combined immunosuppression with cyclosporine and methotrexate in dogs given bone marrow grafts from DLA-haploidentical littermates.

We examined the effect of methotrexate (MTX) combined with cyclosporine (CSP) on the prevention of graft-versus-host disease (GVHD) in dogs. Ten recipients were prepared for grafting with 9 Gy of total-body irradiation and given marrow and buffy coat cells from littermate donors differing for one DLA haplotype (AA leads to AB or AB leads to AC). MTX (0.4 mg/kg) was given i.v. on days 1, 3, 6, and 11. CSP was given i.m. on days 0 to 7 and orally on days 8 to 100. The dose was 15 mg/kg/day on days 0 to 25, 10 mg/kg/day on days 26 to 50, 5 mg/kg/day on days 51 to 75, and 5 mg/kg every other day on days 75 to 100. All ten dogs had sustained engraftment. Three dogs died, one with pneumonia (day 57), one with pneumonia and GVHD (day 107), and one with convulsions (day 204). Seven dogs are surviving at 210 to 493 days, and all are complete chimeras; five are well and two have chronic GVHD that developed after immunosuppressive treatment had been stopped. These results with a combination of MTX and CSP as GVHD prophylaxis are superior to those obtained previously with MTX alone in dogs given marrow grafts from DLA-haploidentical littermates.

Animals↗
PubMed1984

Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease.

Three hundred thirty-two marrow graft recipients and 241 healthy marrow donors were studied by skin testing with recall and neoantigens. Two hundred thirty patients with leukemia and seventy-eight patients with aplastic anemia received allogeneic HLA-identical sibling marrow. Twenty-four patients with leukemia received syngeneic marrow. The conditioning regimen prior to marrow infusion consisted of 120 mg/kg cyclophosphamide and 9.2-15.75 Gy total-body irradiation (leukemia) or 200 mg/kg cyclophosphamide (aplastic anemia). The patients were skin-tested with the neoantigens dinitrochlorobenzene (DNCB), keyhole limpet hemocyanin, and a battery of five recall antigens around 100, 150, 365, 730, 1095, 1460, and 1825 days after grafting. A binary logistic regression analysis was used to investigate the factors thought to influence immunocompetence. At 3 months postgrafting, the proportion of patients positive to DNCB was equal to that of normal marrow donors, but thereafter it was lower until 2 years. The proportion of patients positive to keyhole limpet hemocyanin was lower than normal regardless of the time after grafting. The proportion of patients positive to recall antigens was lower than that of normal marrow donors until 4 years after grafting. Patients with a history of acute graft-versus-host disease had the lowest probability of a positive reaction to recall antigens. None of the other factors was significantly associated with an increased or reduced level of response.

Acute Disease↗
PubMed1984

Lymphocytic bronchitis unrelated to acute graft-versus-host disease in canine marrow graft recipients.

We reviewed coded autopsy material from 71 dogs, 46 receiving allogeneic and 25 receiving autologous bone marrow transplants, to evaluate the hypothesis that lymphocytic bronchitis is associated with severe acute graft-versus-host disease (GVHD). We found no significant correlation between the presence of lymphocytic bronchitis and severe acute GVHD (P greater than 0.16). Using a binary regression model that corrected for possible confounding relationships, we failed to show a correlation between lymphocytic bronchitis and acute GVHD of each of the 3 classically affected organ systems. Also, no correlation was found between lymphocytic bronchitis and acute bacterial pneumonia (P greater than 0.32). Finally, lymphocytic bronchitis was present in autografted dogs with a prevalence at autopsy not significantly different from that of allografted dogs (P greater than 0.32). We conclude that lymphocytic bronchitis in this canine model represents nonspecific inflammation rather than acute pulmonary GVHD.

Acute Disease↗
PubMed1984

Pulmonary bronchoalveolar cell and protein kinetics in dogs given total-body irradiation, autologous marrow grafts, and methotrexate.

Patients receiving allogeneic marrow transplantation for hematologic malignancies commonly are conditioned with total body irradiation (TBI) and given methotrexate (MTX) in an attempt to prevent graft-versus-host disease. To study the effects of TBI with or without MTX on bronchoalveolar cells and proteins, we performed sequential bronchoalveolar lavages in dogs before and after irradiation. Ten dogs received 9 Gy TBI followed by autologous marrow grafts. Six dogs were given no additional treatment and four also received MTX at 0.4 mg/kg on days 1, 3, 6, and 11- and then weekly until day 100. TBI alone resulted in a significant decrease in alveolar macrophages and lymphocytes with recovery after day 30. The addition of MTX resulted in a more profound and prolonged decrease in alveolar macrophages and lymphocytes. The addition of MTX was also associated with a significant increase in alveolar granulocytes with a concomitant rise in lavage protein content in one animal. Lavage fluid IgA levels remained constant. We conclude that the irradiation and chemotherapy used in marrow transplantation has significant pulmonary effects and may contribute to the pulmonary complications following marrow transplantation.

Animals↗
PubMed1984

Regression of androgen-related hepatic tumors in patients with Fanconi's anemia following marrow transplantation.

Two patients with Fanconi's anemia treated for 5 years with oxymetholone developed hepatic function abnormalities in association with hepatic tumors demonstrated by isotope liver-spleen scan or abdominal echogram. The lesions resolved over a period of 26 months after allogeneic marrow transplantation, and the patients are alive and well 3 and 4 years following transplantation. The course of these patients indicates that marrow transplantation for Fanconi's anemia allows the withdrawal of androgens and subsequent regression of androgen-related hepatic tumors in patients who might otherwise have a fatal outcome.

Adolescent↗
PubMed1984

Immunologic recovery in human marrow graft recipients given cyclosporine or methotrexate for the prevention of graft-versus-host disease.

Immunologic recovery was studied in ten patients with aplastic anemia and 23 patients with hematologic malignancy who received HLA-identical marrow grafts and cyclosporine postgrafting as prophylaxis against graft-versus-host disease. Cyclosporine , 12.5 mg/kg/day, was administered beginning on the day before marrow infusion and continued for 50 days, when it was tapered and discontinued by 6 months postgrafting . Results were compared with data from concurrent and previously described patients receiving methotrexate as prophylaxis for graft-versus-host disease. Patients treated with cyclosporine or methotrexate had lower-than-normal immunologic parameters and were not different from one another 3-5 months postgrafting . By 11 to 18 months after grafting lymphocyte counts had normalized in both groups. Serum IgA levels were low and IgG levels had normalized in methotrexate-treated patients, and IgM was normal in cyclosporine -treated patients. In vivo antibody production to T-dependent antigens and skin test responses to recall antigens continued to be impaired. The response to the neoantigen dinitrochlorobenzene was still impaired in patients treated with cyclosporine and normal in patients given methotrexate. These data suggest that immunologic recovery after marrow transplantation is similar in cyclosporine -treated and methotrexate-treated patients.

Antibodies, Viral↗
PubMed1984

Pharmacokinetics of intravenous cyclosporine in bone marrow transplant patients. Comparison of two assay methods.

The influence of assay method on steady-state cyclosporine (CsA) pharmacokinetics was studied in 18 patients with leukemia or aplastic anemia undergoing allogeneic marrow transplantation who received i.v. CsA for prophylaxis or treatment of graft-versus-host disease. Since CsA is extensively metabolized and subject to biliary elimination, CsA courses were divided according to the presence (serum bilirubin greater than 2.0 mg/dl) or absence (serum bilirubin less than or equal to 1.2 mg/dl) of hepatic dysfunction. All patients had normal renal function. Serum CsA concentrations were measured concurrently by radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC). Serum concentration-time data were analyzed by standard nonlinear regression methods. Systemic clearance (Cls) calculated from HPLC results was higher than that derived from RIA results, regardless of hepatic function (P less than 0.05). These data indicate that results obtained by RIA overestimate CSP concentrations, presumably because of the presence of crossreactive CSP metabolites. These differences can significantly affect derived pharmacokinetic parameters. Therefore, clinicians who make dosage recommendations based on pharmacokinetic parameters should consider the effect of assay method.

Anemia, Aplastic↗
PubMed1984

Indications for marrow transplantation.

Marrow grafting, originally considered only for end-stage patients after failure of all other treatment, is now the treatment of choice for a variety of malignant and nonmalignant diseases. Donor and recipient selection and the results of marrow transplantation for various diseases and stages of diseases are summarized.

Acute Disease↗
PubMed1984

Graft-versus-host disease: pathophysiological and clinical aspects.

Graft-versus-host disease (GVHD) is a syndrome observed after allogeneic marrow transplantation and presumably mediated by donor T lymphocytes reactive against the tissues of the recipient. Clinically relevant acute GVHD develops in 35-50% of patients given HLA-identical marrow grafts within the first 100 days of transplantation. The main target organs are skin, liver, and intestinal tract. Approximately one half of the patients with moderately severe to severe disease die, usually from associated infections. Prevention of acute GVHD by placing the patient in protective isolation, immunosuppressive treatment after grafting, or removal of donor lymphocytes from the marrow inoculum has, as yet, not been uniformly successful. Treatment of established GVHD involves the use of immunosuppressants such as glucocorticosteroids, antithymocyte globulin, cyclosporine, and monoclonal antibodies. Chronic GVHD usually develops 100-500 days after transplantation and affects about 45% of all long-term survivors. The main target organs are the same as those of acute GVHD and, in addition, lacrimal and salivary glands, and mucous and serous membranes; the clinical picture resembles that of a number of collagen-vascular diseases. The incidence of chronic GVHD is higher in patients with previous acute GVHD and it increases with patient age. Treatment involves immunosuppressive and cytotoxic drugs. Patients are highly susceptible to bacterial and fungal infections that are lethal in a small proportion of patients.

Anemia, Aplastic↗
PubMed1984

Allogeneic marrow transplantation.

After 15 years of clinical investigation, allogeneic marrow transplantation can be considered the treatment of choice for a variety of hematologic and immunologic diseases. This review has focused upon some of the principles, current results, problems, and future directions in allogeneic marrow grafting.

Acute Disease↗