PubMed Health⌕ Search

Biomedical subjects

G Ehninger

Publications and source records attributed to G Ehninger.

At least 199 records · Page 11Linked to original sources
PubMed1993

Thalidomide--the need for a new clinical evaluation of an old drug.

Thalidomide shows activity in refractory chronic graft-versus-host disease. Best responses were seen in mucocutaneous disease. The studies vary in inclusion criteria (e.g. pretreatment), time of onset of GVHD and dose given. The optimal schedule of thalidomide treatment is not defined. The role of thalidomide must be assessed in large controlled trials for treatment and prophylaxis of GvHD. Due to the variable absorption rate there is a need for an intravenous formulation of thalidomide, and in addition the search for more active and possibly less teratogenic derivatives must be intensified.

Graft vs Host Disease↗
PubMed1993

Pentamidine aerosol for prophylaxis of Pneumocystis carinii pneumonia after BMT.

Following BMT there is a 5-15% risk of interstitial pneumonia caused by Pneumocystis carinii (PcP). Cotrimoxazole is therefore administered prophylactically, but may cause myelodepression, allergic reactions and nephrotoxicity. As PcP prophylaxis with pentamidine aerosol is effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate toxicity, safety, practicability and possible resorption of aerosolized pentamidine. We treated 31 allogeneic and 12 autologous BMT patients with 60 mg pentamidine 3 days before and 14 days after BMT. Starting 4 weeks after BMT, 300 mg pentamidine was given every 4 weeks for 6 months. There was no pneumonia caused by Pneumocystis carinii. The only noteworthy side-effects were cough (19.8%), salivation (9.6%), and sore throat (5.7%), of similar frequency after allogeneic or autologous BMT. Using high pressure liquid chromatography, pentamidine could only be detected in the serum of 33-54% of patients tested. In these patients the median serum levels were 7.5-9 ng/ml. We conclude that pentamidine aerosol has only minor side-effects, is well tolerated and safe, and is therefore an attractive alternative for PcP prophylaxis after BMT.

Administration, Inhalation↗
PubMed1992

Prevention of viral infections after bone marrow transplantation.

After bone marrow transplantation, a number of viral infections contribute to the morbidity and mortality of the procedure. Established preventive measures to avoid primary infection and reactivation of herpes-and cytomegaloviruses are outlined. Possible future strategies against these viruses (e. g., monoclonal antibodies, transfer of T-lymphocytes) and the possible role of improved diagnostic tools are briefly discussed.

Bone Marrow Transplantation↗
PubMed1992

IL2- and IL4-dependent proliferation of T-cell clones derived early after allogeneic bone marrow transplantation: studies of patients with chronic myelogenous leukaemia.

In an attempt to explore T-cell functions shortly after allogeneic bone marrow transplantation more fully, IL2- and IL4-dependent proliferation was assessed on CD4+ TCR alpha beta+ T-cell clones derived 4-6 weeks after transplantation. Both allogeneic pooled peripheral blood mononuclear cells and Epstein-Barr virus-transformed B-cell lines (BCL) could function as accessory cells (AC) for PHA activation of T-cell clones. Although minimal clonal proliferation was seen when the T-cell activation signal was BCL+PHA+IL4, a majority of the clones could undergo IL4-dependent proliferation after previous activation with AC+PHA+IL2. For certain clones, IL4 also showed an additive effect with IL2. Thus, IL4 was a growth factor for a majority of the investigated posttransplant T-cell clones, and in vivo modulation of IL4-dependent T-cell functions may thus become a future therapeutic possibility to enhance graft-versus-leukaemia effects in bone marrow transplant recipients.

Antigen-Presenting Cells↗
PubMed1992

[Determinants of serum pentamidine concentration in the human].

By means of serial measurements of pentamidine in plasma, urine and feces the significance of biologically available dose, volume of distribution, elimination and dose interval for serum concentration is investigated in patients with AIDS and bone marrow transplantation after inhaled and intravenous application. Aerosolisation of the drug yields to serum concentration mostly below the detection limit (HPLC). In urine only 0.15 to 0.8% of the substance biologically available in the lung are measured as unaltered pentamidine-base. After i.v. infusion the dose dependent low serum concentrations of 30 to 100 ng/ml indicate a fast distribution in peripheral compartments from which a very slow deliberation is seen. The half-life of the drug is also dose dependent and amounts under clinical conditions at minimum four days. The fecal excretion is found to be only one third of that measured in urine. A difference in the kinetic of elimination between bone marrow transplantated and AIDS-patients could not be evaluated. For clinical therapy the most important pharmacokinetic variable seems to be the terminal elimination constant which would implicate a prolongation of the common dose interval.

AIDS-Related Opportunistic Infections↗
PubMed1992

[Risk factors and prevention of pneumocystis carinii pneumonia after bone marrow transplantation].

For six months after bone marrow transplantation (BMT) there is a risk of 5 to 15% to suffer from interstitial pneumonia due to pneumocystis carinii (PcP). Prophylaxis with trimethoprim/sulfamethoxazol is therefore routinely and successfully applied. However myelotoxicity, allergic reactions, augmentation of the risk of nephrotoxicity with cyclosporine A and noncompliance may be serious problems. Since the prophylaxis of PcP with pentamidine-aerosol proved to be effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate the toxicity, safety, practicability and possible resorption of pentamidine when applied as aerosol. The first of 43 patients were treated with 60 mg pentamidine on two days before, at the day of BMT and 14 days after BMT. Starting four weeks after BMT, 300 mg pentamidine were given every four weeks up to six months. After the study, the four 60 mg inhalations were replaced by two 300 mg inhalations before BMT, because this proved to be more convenient for the patients. There was no pneumonia due to pneumocystis carinii. The only noteworthy side effects observed were cough (19.8%), salivation (9.6%) and sore throat (5.7%). In general pentamidine was well tolerated and well accepted by the patients. Pentamidine could only be detected in the serum of 40 to 60% of all patients. In those patients the serum levels were 7.5 to 9 ng/ml and similar to concentrations found in comparable patients with AIDS. We conclude, that pentamidine-aerosol has only minor side effects, is well tolerated and safe and is therefore an attractive alternative for PcP-prophylaxis after BMT.

Administration, Inhalation↗
PubMed1992

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

Adolescent↗
PubMed1992

Intracellular cytosine arabinoside accumulation and cytosine arabinoside triphosphate formation in leukemic blast cells is inhibited by etoposide and teniposide.

Cytosine arabinoside (ara-C) is one of the most active compounds in the treatment of acute leukemias. In the majority of current protocols ara-C is combined with other cytotoxic agents in an attempt to increase antileukemic activity. The present study investigated the impact of etoposide, teniposide, amsacrine, mitoxantrone, anthracyclines, and asparaginase on the cellular accumulation of ara-C and its intracellular metabolism in order to provide a better rationale for combination therapy. Intracellular accumulation and phosphorylation of ara-C were determined in peripheral blast cells from twenty patients with acute leukemias after exposure to 1 and 10 mumol/l ara-C alone and after preincubation with 1 and 10 micrograms/ml etoposide, 10 and 100 micrograms/ml teniposide, 10 mumol/l amsacrine, 500 ng/ml mitoxantrone (or daunorubicin or doxorubicin) or 10 mumol/l asparaginase. Ara-C accumulation at 10 mumol/l was decreased by 1 microgram/ml etoposide (67 +/- 18% of control), 10 micrograms/ml etoposide (30 +/- 22%), 10 micrograms/ml teniposide (12 +/- 23%), 100 micrograms/ml teniposide (10 +/- 18%), and amsacrine (51 +/- 21%). Intracellular ara-CTP formation was determined at an extracellular concentration of 10 mumol/l and preincubation with these drugs. The intracellular formation of ara-CTP was decreased by 1 microgram/ml etoposide (77 +/- 15% of control), 10 micrograms/ml etoposide (32 +/- 22%), 10 micrograms/ml teniposide (10 +/- 9%), 100 micrograms/ml teniposide (0 +/- 0%), but not by amsacrine. These data indicate that prior exposure to etoposide and teniposide influence ara-C metabolism and possibly cytotoxicity, and thus should not immediately precede ara-C administration in clinical trials.

Acute Disease↗
PubMed1992

[Juvenile chronic leukemia and chronic myelomonocytic leukemia. Experiences with bone marrow transplantation in childhood in 5 cases].

Chronic leukemias of early childhood (JCML/CMML) are rare malignant diseases for which effective regimens of chemotherapy have not been established. However, some of these patients may be cured by BMT. We report on 4 children with JCML and one child with CMML undergoing BMT from HLA-identical siblings and from matched unrelated donors. 3 of 5 patients are disease-free 9 to 37 months post BMT. According to our observations an effective reduction of blastic cells before BMT seems to be necessary for a sustained remission of these diseases. This reduction can be reached by intensive chemotherapy and by splenectomy before BMT. Moreover, we stress the need for total body irradiation (TBI) during BMT in order to eradicate residual malignant cells.

Blood Cell Count↗
PubMed1991

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study.

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).

Adolescent↗
PubMed1991

Polymerase chain reaction to evaluate antiviral therapy for cytomegalovirus disease.

A sensitive and specific method to monitor suppression of cytomegalovirus (CMV) replication is essential in patients treated with ganciclovir after allogeneic bone-marrow transplantation. In this study, antiviral therapy of eighteen episodes of symptomatic CMV infection in 15 such patients were followed up clinically and by virus culture and polymerase chain reaction (PCR). Clinical improvement, culture, and PCR were assessed for their ability to predict the efficacy of ganciclovir therapy in each patient. In eleven successfully treated episodes of CMV disease (disappearance of symptoms and improvement in biochemical variables) clinical improvement was associated with an effective suppression of virus replication as shown by negative culture and PCR assays of blood and urine specimens obtained after antiviral therapy. 1 patient who did not improve clinically when receiving antiviral therapy remained both culture positive and PCR positive for CMV. 6 patients with early relapse of CMV disease or who died after an initial clinical improvement were PCR positive but culture negative after termination of therapy. Demonstration of CMV in blood and urine by PCR after stopping antiviral therapy (even when culture is negative) points to incomplete suppression of virus replication. The findings show that PCR is a better predictor of the efficacy of antiviral therapy than are culture or clinical assessment.

Adult↗
PubMed1991

Isolation and structure elucidation of urinary metabolites of mitoxantrone.

Three 13C-labeled 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]-ethyl)amino-9,10- anthracenedione dihydrochloride (mitoxantrone) isotopomers were synthesized to prove the proposed chemical structures of human urinary metabolites by means of nuclear magnetic resonance spectroscopy. After application of labeled mitoxantrone to an anesthetized pig, urine was collected by way of a vesicourethral catheter. The urinary metabolites were isolated by liquid chromatography using a new procedure developed for extraction of mitoxantrone metabolites. Structural elucidation by nuclear magnetic resonance spectroscopy and tandem mass spectrometry confirmed the proposed mono- and dicarboxylic acid structures of the metabolites. High-performance liquid chromatography of native pig urine showed an additional metabolite detected by its UV-visible absorption. The new metabolite was identified as a glucuronic acid conjugate of mitoxantrone by means of nuclear magnetic resonance spectroscopy and tandem mass spectrometry. Incubation with beta-glucuronidase under high-performance liquid chromatography control revealed mitoxantrone as the sole product. Quantitative high-performance liquid chromatography analyses showed that the new urinary metabolite represents the main biotransformational pathway of mitoxantrone in pigs, indicating significant interspecies variation in mitoxantrone biotransformation. Expressed in equivalents of mitoxantrone, the new metabolite amounts to 25% and 31%, respectively, of urinary excreted drug-related material. Extraction of patient urine using the same procedure led to the isolation of pure metabolite B. Tandem mass spectrometric data delivered definitive evidence for the structure of metabolite B as monocarboxylic acid of mitoxantrone.

Animals↗
PubMed1991

Early occurrence of human cytomegalovirus infection after bone marrow transplantation as demonstrated by the polymerase chain reaction technique.

Twenty-eight patients undergoing bone marrow transplantation (BMT) were followed-up at weekly intervals from day -10 to discharge from hospital after BMT for human cytomegalovirus (HCMV) infection using polymerase chain reaction (PCR), slot-blot hybridization, and conventional virus culture. High specificity of the PCR assay applied could be shown by failure to amplify DNA extracted from a wide range of other viruses frequently infecting marrow transplant recipients. The PCR technique allowed us to diagnose viremia and viruria in 20 (83%) of 24 seropositive patients after BMT, whereas culture assays showed 16 (67%) of 24 of these patients to be viruric and 9 (37%) of 24 cases to be viremic. Slot-blot hybridization showed a frequency of viruria and viremia in 12 (50%) of 24 seropositive patients. By application of PCR techniques, HCMV detection could be achieved even in the very early posttransplant period. HCMV was detected in five patients even before the onset of clinical symptoms of acute graft-versus-host disease. Analysis by PCR techniques of 33 organ biopsy specimens from patients after BMT showed the presence of HCMV in 13 of 14 liver samples obtained from patients with HCMV viremia; three liver specimens from patients without viremia were negative by all the techniques applied. HCMV could also be demonstrated in postmortem lung biopsy specimens from all patients (n = 10) with interstitial pneumonia.

Bone Marrow Transplantation↗