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Biomedical subjects

R Dopfer

Publications and source records attributed to R Dopfer.

At least 73 records · Page 4Linked to original sources
PubMed1988

Prevention of CMV infection after BMT in high-risk patients using CMV hyperimmune globulin.

Prophylactic administration of an intravenous cytomegalovirus hyperimmune globulin in bone marrow transplant recipients provided protection against primary as well as reactivated CMV infection in patients considered to be at high risk for cytomegalovirus infections. Forty-one patients were divided in six subgroups according to factors considered to increase the incidence and severity of CMV infections following bone marrow transplantation. All of these patients received blood products from donors not screened for active or latent CMV infections. In spite of this, patients undergoing intensified conditioning therapy or mismatch transplantation, as well as those transplanted in relapse of their leukemia and even patients receiving granulocyte transfusions from donors unscreened for CMV serostatus, were found not to develop primary or secondary CMV infections. Only in the group of patients older than 35 years and among those suffering from severe GVHD six patients were found to have CMV infections, only two a symptomatic form. Intravenous administration of CMV hyperimmune globulin effectively protected even patients at high risk for CMV infection against severe complications of primary infection or reactivation of this virus.

Adult↗
PubMed1988

Significant reduction of cytomegalovirus (CMV) disease by prophylaxis with CMV hyperimmune globulin plus oral acyclovir.

The effect of prophylactic intravenous administration of a cytomegalovirus (CMV) hyperimmune globulin with a high titer of neutralizing antibodies plus oral acyclovir was studied in 93 consecutive bone marrow transplant recipients. In spite of receiving blood products unscreened for CMV only six patients developed CMV infections during the time they received passive immunization. Five patients reactivated virus after hyperimmune globulin infusions were stopped; four of them suffered from chronic graft-versus-host disease (GVHD) Among the patients suffering from acute GVHD grade III/IV and/or chronic GVHD the incidence of CMV infection (10/38) was significantly higher than among those with no or milder forms of GVHD (1/55) (p less than 0.01). Only three patients suffered from symptomatic CMV infections; two with gastrointestinal manifestations and one with fatal CMV pneumonia. Thus CMV prophylaxis as used here proved highly effective in combating one of the major difficulties encountered in BMT.

Acyclovir↗
PubMed1988

A case of accidental cyclosporin overdose with pharmacokinetic analysis.

In a case of oral overdose of cyclosporin we measured plasma concentrations by radioimmunoassay and high pressure liquid chromatography. We observed unchanged pharmacokinetic parameters after the overdose indicating normal renal and hepatic function. Laboratory findings showed no renal or hepatic damage. As toxic symptoms, only emesis and a short, mild drowsiness were noted.

Bone Marrow Transplantation↗
PubMed1988

MIBG-treatment in neuroblastoma; experiences of the Tübingen/Frankfurt group.

27 children with neuroblastoma were treated with 131I-Metaiodobenzylguanidine (MBIG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were evaluable for analysis of results. In 4 children (16.7%) a CR was observed, in 10 (41.7%) a PR, in 5 (20.8%) a disease stabilization and 5 were nonresponders. The 4 CR-patients were initially stage IV. 3 of them were treated in addition by bone marrow transplantation (bmt), one by further chemotherapy. 3 died of a relapse, 1 of complications from bmt. 5 of the 10 PR-patients died of tumor progression, 3 achieved a CR by additional chemotherapy, 1 a PR by bmt and 1 stays in PR without further measures. 2 of the 5 children with a disease stabilization were the first treated patients to whom a fairly low dose was given. In 3 of the 5 nonresponders no uptake of MIBG was observed; they died from tumor progression. 1 of the 2 nonresponders with uptake died of graft-versus-host disease after bmt, 1 other also of tumor progression. Duration of remission was between 1 and 12 months and depended upon uptake and dose of MIBG, interval between administrations and individual tumor behaviour. Side effects were seen as marked bone marrow depression; this was reversible in any case and we did not loose a patient due to MIBG-induced leuko- or thrombopenia. In cases of severely ill children we observed a very fast and dramatical amelioration in clinical conditions. With this method even in neuroblastoma relapse and in nonresponders complete remissions are achievable. Important is the intensification of the therapeutical effect by additional chemotherapy or in combination with bmt. For a definitive evaluation further investigations are necessary to optimize therapeutic strategies.

3-Iodobenzylguanidine↗
PubMed1987

[Functions of intrinsic defense against anaerobic bacteria in healthy probands and patients with chronic-septic granulomatosis].

Different strains of Bacteroides fragilis exhibit great differences in sensitivity towards serum from healthy volunteers. In the presence of 10% autologous serum, neutrophilic granulocytes and monocytes (macrophages) caused significant killing of B. fragilis. The measured phagocytic and killing activity of the cells is comparable to their activity against aerobic bacteria (S. aureus). In four patients with chronic granulomatous disease of childhood, phagocytosis was normal but killing of B. fragilis and S. aureus in granulocytes or monocytes (macrophages) was appreciably lowered. This malfunction of the cells was accompanied by a disturbance in oxidative metabolism and inadequate iodination after phagocytosis of B. fragilis. The results suggest that granulocytes and monocytes play an important role in host defense against endogenous infections with anaerobes.

Abscess↗
PubMed1987

Aggressive combination chemotherapy of bone marrow relapse in childhood acute lymphoblastic leukemia containing aclacinomycin-A: a multicentric trial.

An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.

Aclarubicin↗
PubMed1987

Successful bone marrow transplantation from an unrelated donor in a child with AML in second remission.

In February 1986 we transplanted a 10-year-old girl with AML in second remission with the bone marrow of an unrelated donor. HLA-types were different for one A- and one B-antigen between patient and donor. Conditioning regimen consisted of 14 Gy total body irradiation with lung shielding, 8 X 3 g/m2 cytosin arabinoside and 90 mg/kg cyclophosphamide. GVHD-prophylaxis was performed with cyclosporin A, methotrexate and prednisolone. Only mild GVHD I of the skin could be observed after rapid engraftment. 100 days after transplantation the patient was in good clinical condition and GVHD-prophylaxis was discontinued without any reactivation of acute or chronic GVHD. Engraftment was documented by sex chromosome and blood group typing. 120 days after transplantation leukemic blasts were detected in the peripheral blood and the child died 130 days after BMT from relapse of the leukemia. Despite the negative outcome, this was the first successful bone marrow transplantation from a unrelated donor in Germany.

Bone Marrow Transplantation↗
PubMed1987

Kinetics of restoration of interferon production after bone marrow transplantation in man.

Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Pregnancy after bone marrow transplantation for severe aplastic anemia.

Two women suffering from severe aplastic anemia were treated by bone marrow transplantation (BMT). They became pregnant 17 and 40 months after the procedure. During the first 20 weeks of pregnancy, one of them continued to receive cyclosporin A (CSA) to prevent graft-versus-host disease. Her CSA serum levels during these first 4 months ranged from 35 to 280 ng/ml. The course of pregnancy was uneventful and a healthy boy was delivered at term by Cesarean section. The other patient was shown to have rejected the transplanted marrow 4 months after BMT; autologous regeneration had occurred. During the last 2 months of her pregnancy, the hemoglobin and platelet numbers decreased again. Nevertheless, a healthy girl was delivered at term. Three months after delivery this patient's hematologic parameters are almost back to normal.

Anemia, Aplastic↗
PubMed1986

[Oral prophylaxis of herpes infections using acyclovir following bone marrow transplantation: a clinical and clinico-pharmacological study].

Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day -12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.

Acyclovir↗
PubMed1986

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗
PubMed1986

[Bone marrow transplantation in severe aplastic anemia].

Bone marrow transplantations were performed on 15 patients (aged 5-39 years) with severe aplastic anaemia. Twelve patients are alive 76-1930 days (median 668 d) after transplantation, with complete haematopoetic recovery. Total-body radiation with 3.6 Gy in four patients, cyclosporin A administration to ten patients and buffy-coat transfusion to nine patients entirely prevented early rejection. Two patients died of pneumonia (aspergillus; varicella-zoster virus), one patient died of bleeding from a splenic-artery aneurysm. In patients under the age of 40 years with severe aplastic anaemia bone marrow transplantation as early as possible after diagnosis is the treatment of choice if HLA-identical siblings are available as donors. In patients over 40 years treatment should at first be tried with antithymocyte globulin.

Acute Disease↗
PubMed1986

Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine.

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.

3-Iodobenzylguanidine↗
PubMed1986

Appearance of an inherited porphyria cutanea tarda in a child after allogeneic bone marrow transplantation for chronic myelogenous leukaemia.

We report details of a 6 1/2-year-old girl who developed porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. The results of studying porphyrin metabolism in the family members are described. Expression of the disease may have been induced by the cyclophosphamide and total-body irradiation in the conditioning regimen and/or by the administration of methotrexate for the prevention of graft-versus-host disease and meningeal leukaemia.

Bone Marrow Transplantation↗