PubMed Health⌕ Search

Biomedical subjects

U W Schaefer

Publications and source records attributed to U W Schaefer.

At least 91 records · Page 5Linked to original sources
PubMed1991

High-dose 1,2,4-triglycidylurazol given in regimens preparatory to bone marrow transplantation. A preclinical pharmacology study.

To elucidate its potential role in the framework of bone marrow transplantation, we studied the toxicologic and pharmacologic properties of high doses of the triepoxide derivate 1,2,4-triglycidylurazol (TGU) in a preclinical dog model. Dose-dependent and dose-limiting gastrointestinal toxicity occurred in a dose range between 40 and 75 mg/kg, with the lethal dose for 50% of animals (LD50) being estimated at 60 mg/kg. Severe and life-threatening hematologic toxicity developed at all dose levels examined but was generally reversible. The combination of TGU and total-body irradiation produced synergistic gastrointestinal toxicity, necessitating reductions of the TGU dose by 50% as compared with the single-agent dose. In contrast, the combination of TGU and high-dose busulfan resulted in no apparent nonhematologic synergistic toxicities. The immunosuppressive properties of TGU given in this combination enabled sustained histocompatible allogeneic marrow engraftment in three of four animals. The pharmacokinetics of TGU were not influenced by prior total-body irradiation or high-dose busulfan. We conclude that the myelotoxic, pharmacologic and immunosuppressive properties of high-dose TGU observed in this preclinical model seem to render the drug particularly suitable for use in regimens preparatory to bone marrow transplantation.

Animals↗
PubMed1991

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human alpha/beta T cell receptor.

A murine IgG2b monoclonal antibody directed to the constant part of the human alpha/beta T cell receptor (BMA031) was investigated in a pilot study as an initial treatment for acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation. The treatment protocol consisted of 5 mg BMA031 on 5 consecutive days with continuation of the prophylactic baseline immuno suppression using cyclosporin. Seven patients with grades II-III acute graft-versus-host disease were entered on the protocol and six patients completed the full treatment course. Mild to moderate acute adverse reactions to the first BMA031 infusion occurred in three patients. A nearly complete decline of circulating T lymphocytes was observed during BMA031 therapy, but the T cells returned to pretreatment values within 1 week after the last infusion. Serum pharmacokinetics of free antibody best fitted to a two-compartment open model with a mean initial half-life of 6 h and an estimated mean terminal half-life of 40 h. One patient developed antimurine antibodies of the IgM subclass. In five patients a complete and sustained resolution of all disease manifestations was attained, while in one patient a temporary response of skin involvement with aGvHD was noted. These results indicate that BMA031 can be safely administered as initial treatment of aGvHD. The therapeutic responses observed warrant its further clinical evaluation in this setting.

Acute Disease↗
PubMed1991

[Roentgen diagnosis of pulmonary complications following allogeneic bone marrow transplantation--application of and experience with digital luminescence radiography].

Pulmonary complications exercise a decisive influence on the prognosis of leukaemia patients after bone marrow transplantation. Very early diagnosis is a mandatory prerequisite to successful therapeutic intervention. Of great importance besides the clinical findings and bronchoalveolar lavage is the analysis of the x-ray morphology of pneumonic infiltrates to narrow down the differential diagnostic spectrum. Since the patients are at high risk of infection, they are under isolated care, so that x-ray examinations can only be performed by means of projection radiography using mobile units. Due to these difficulties in performing relevant radiography the required optimal and constant image quality cannot be achieved by means of conventional x-ray film, so that very early detection of pulmonary complications is not always possible. The use of digital luminescence radiography (DLR) with luminescent storage foils enables a highly constant and hence comparable image quality thanks to increased image dynamics, a larger area of the examined object, and histogram evaluation of the image data for determining the optimal parameters for assessment. In addition, details can be better identified to supply answers to specific questions, because the image can be reprocessed to select relevant image parameters by monitoring. Pulmonary complications in 86 patients were analysed retrospectively. These patients had received an allogeneic bone marrow transplant for acute myeloic leukaemia, after they had been treated with high-dose radio-/chemotherapy. The x-ray morphology, clinical and sometimes autopsy findings were correlated with the occurrence of pulmonary complications subsequent to bone marrow transplant.

Adolescent↗
PubMed1990

Clinical results and the Essen concept of TBI.

Total body irradiation (TBI) prior to bone marrow transplantation (BMT) is applied for treatment of 230 patients in the period 1975-1988. The clinical results of 169 patients treated by four different TBI dosage and treatment techniques are analysed. The risk of leukemic relapse is low after fractionated TBI (9%) as well as after single dose TBI (14%). The lowest frequency of interstitial pneumonitis (21%) occurred when the patient translation technique was used for fractionated homogeneous pa/ap TBI with 10 Gy (8 Gy lung dose) in 4 fractions in 4 days. Prophylaxis of GVHD and the modus of protective environment were two other factors which influence the risk of IP.

Adult↗
PubMed1990

Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation.

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.

Acute Disease↗
PubMed1990

[Experiences with transfusion of CMV tested blood preparations after bone marrow transplantation].

Cytomegalovirus infections are frequent and often life-threatening in bone marrow transplant recipients. Among 112 of our patients after bone marrow transplantation (BMT), 28 developed clinical symptoms or laboratory test results of CMV infection, and 15 of them died. In our experience blood cell substitution with products from CMV negative blood donors does not completely prevent CMV infections. Other factors like disturbances of immunoreconstitution after BMT are relevant in promoting the development of CMV disease.

Antibodies, Viral↗
PubMed1990

[Erythrocyte substitution and isoagglutinin titer following ABO-incompatible bone marrow transplantation].

About 2 or 3 weeks after transplantation, even ABO-Incompatible bone marrow shows a successful graft. Haemopoiesis is not always free of problems. Suppression of erythropoiesis is caused by persistently incompatible agglutinins. Patient's well-being is limited by longer periods of low levels of haemoglobin concentration. Long-lasting need for transfusions is related to the well-known risk of infections. A procedure to eliminate the residual titers of alloantibodies should be discussed in time with the staff of the transfusion department.

ABO Blood-Group System↗
PubMed1990

[Prophylaxis and therapy of fungal infections with fluconazole in patients after bone marrow transplantation].

In an open study 31 patients undergoing bone marrow transplantation for various haematological diseases received fluconazole as prophylaxis or treatment of fungal infections. In 26 of these patients an antecedent oral prophylaxis with polyene antimycotics had failed to prevent infections with Candida species. Five of the 31 patients received fluconazole as primary prophylaxis because of non-compliance for polyene antimycotics. Fluconazole was administered orally at a daily dose of 100 mg and 200 mg, respectively (n = 29), or intravenously at a dose of 100 mg and 400 mg (n = 2). Cure or efficient prophylaxis was achieved in 22/31 patients (71%) after a median of 52 (9 to 546+) treatment days. In three patients (10%) Candida was eradicated but the infection reappeared 14-28 days after cessation of the drug; in 6 patients (20%) the infection was persistent or progressive. Four patients developed lethal Aspergillus infection while on fluconazole medication. A moderate and reversible elevation of liver function tests under therapy was observed in 9 patients and was possibly attributable to fluconazole in 3 of them (10%). One patient developed tremor which resolved after cessation of fluconazole. No other adverse drug reactions could be noted. We conclude that fluconazole is a relatively safe and effective drug for the prevention and treatment of superficial and, possibly, deep Candida infections in severely immunocompromised patients. It is presumably without preventive value in Aspergillus infections.

Adult↗
PubMed1989

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia.

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).

Adult↗
PubMed1988

Translocation t(8;16) in acute monocytic leukemia.

A report is given of three new cases of acute monocytic leukemia, FAB M5a, with a t(8;16)(p11;p13). Two cases showed a marked erythrophagocytosis, including one with phagocytosis of normoblasts and granulocytes. Phagocytosis was absent in the third case. The t(8;16) was the only abnormality in two cases, whereas one case showed clonal evolution with partial trisomy 1q and a deletion of part of the short arms of chromosomes 1 and 3. Treatment results and survival were poor in all cases. A complete remission was achieved in two patients, which lasted only for 3 and 6 months, respectively. In one of these cases a central nervous system relapse occurred. Survival was short, lasting between 1 and 9 months. One patient succumbed to interstitial pneumonitis, a complication of allogeneic bone marrow transplantation without evidence for relapsing leukemia.

Adult↗
PubMed1988

Bone marrow transplantation for myeloblastoma.

A 20-yr-old man with bulky mediastinal and retroperitoneal tumour masses identified as myeloblastoma is described. After a partial remission was induced by aggressive chemotherapy, mediastinal irradiation and retroperitoneal tumour resection, the patient received an allogeneic marrow graft from his HLA-identical sister. The conditioning regimen consisted of high-dose busulfan and cyclophosphamide. The patient has a well-controlled secondary chronic graft-versus-host disease. He is in unmaintained complete remission and in good general condition at 20 months post-transplantation.

Adult↗
PubMed1988

Treatment of acute graft-versus-host disease after HLA-partially matched marrow transplantation with a monoclonal antibody (BMA031) against the T cell receptor. First results of a phase-I/II trial.

As part of an ongoing phase-I/II trial, 2 patients received a 5-day treatment course with a murine monoclonal antibody (MAB) directed against the human T cell receptor (BMA031) as primary therapy of acute grade III skin and gastro-intestinal graft-versus-host disease (GvHD) occurring after allogeneic bone marrow transplantation (BMT). All MAB infusions were tolerated without side effects. A complete response of all symptoms of acute GvHD could be attained by MAB therapy under a continued baseline immunosuppression with cyclosporin (CSP), and both patients remain alive and disease-free at 7 and 8 months after therapy without evidence of chronic GvHD. Although the exact treatment scheme has still to be defined, we conclude that this MAB may be useful as primary therapy of acute GvHD. However, the potential hazards of 'in vivo' therapy with MABs directed against T lymphocytes call for a critical evaluation of this treatment modality.

Adult↗
PubMed1988

[Bone marrow transplantation at the Essen University Clinic].

From December 1975 until October 1988 292 bone marrow transplantations (bmt) have been performed at the Center for Tumor Research and Tumor Therapy, University Hospital Essen; 251 of these transplantations were allogeneic, 30 autologous and 11 syngeneic. The main indications were ALL (n = 39), AML (n = 132), CML (n = 75) and severe aplastic anemia (n = 26). Now the transplantation rate is one bmt per week. Early transplantation during a controlled stage of disease provides the best chance of cure. Important prerequisites of a successful allotransplantation are patient age under 45-50 years, good general condition and a histocompatible donor. In case of autologous bmt, being mainly tested in acute leukemias and malignant lymphomas, the age limit is 50-55 years. If the allogeneic transplantation is performed during an early stage of disease, the cure expectancy is about 50% for acute leukemia in first remission and CML in chronic phase. In the case of severe aplastic anemia the cure rates are even higher, provided that the transplant is grafted before multiple blood transfusions have been given. In AML the risk of relapse after autologous bmt is higher than after allogeneic transplantation, but the preliminary data are promising. The question of whether or not autologous bmt is superior to conventional chemotherapy of AML, has to be investigated.

Adolescent↗