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Biomedical subjects

G Ehninger

Publications and source records attributed to G Ehninger.

At least 271 records · Page 15Linked to original sources
PubMed1988

Cellular immunological defects of chronic myelogenous leukaemics: partial dependence on busulphan therapy.

The PBMC from treated (n = 10) and untreated (n = 7) chronic phase CML patients were examined for their functional expression of helper cell-stimulating class II products, HLA-DR and -DP, and for their ability to induce suppression in normal PBMC. Although DR and DP were found to be functionally expressed in both groups of patients, a dysregulation of suppression induction was found in treated but not in untreated patients. Furthermore, the patients demonstrated a virtual absence of NK activity and severely depressed LAK activity which was equally striking in both treated and untreated patients and did not seem to be related to the presence of active suppression of cytotoxicity. Such defects in chronic phase CML patients may be relevant to the progression of their disease. Moreover, at least one of the cellular immunological defects, induction of suppressive cells, was not intrinsic to the disease, but appeared to be chemotherapy related.

Antigens, Differentiation↗
PubMed1988

Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation.

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.

Acute Disease↗
PubMed1988

Lymph node morphology after allogeneic bone marrow transplantation for chronic myeloid leukemia: a histological and immunohistological study focusing on the phenotype of the recovering lymphoid cells.

A histological and immunohistological analysis of lymph nodes after allogeneic bone marrow transplantation (BMT) was performed to investigate the microarchitecture of the lymphatic tissue and the phenotype of the recovering lymphoid cells. The study included four patients with chronic myeloid leukaemia who had died between 0.5 and 12 months after transplantation. The study yielded the following results: 1. All lymph nodes, irrespective of length of the survival period, exhibited severe atrophy of the lymphoreticular tissue with marked depletion of lymphocytes and dilatation of the sinuses. The number of lymphoid cells increased considerably with time after transplantation. 2. The main constituents of the recovering immune system were mature T lymphocytes (CD4+ and CD8+ cells in nearly equal numbers) and macrophages. The earliest signs of recovery of the immune system could already be detected 0.5 month after BMT. 3. Extreme paucity of B lymphocytes was a prominent finding in all lymph nodes studied. True lymphatic follicles and germinal centres were never detected. 4. Polytypic plasma cells were seen in low or moderate numbers mainly in the lymph node sinuses, while neither marked plasmacytic hyperplasia nor even a monotypic pattern were found. 5. Immune-accessory reticulum cells were detected only in the lymph nodes of the patient who survived 12 months. 6. Natural killer cells occurred only in low numbers irrespective of the duration of survival after BMT. Altogether, the histopathological lymph node findings clearly reflect the marked long-standing depression of the immune responses seen after allogeneic bone marrow transplantation. Since three of the four patients had shown signs of acute or chronic graft-versus-host disease, the histological findings presumably do not fully reflect the normal reconstitution of the immune system, but may have been modified by phenomena related to graft-versus-host disease.

Adolescent↗
PubMed1988

Escalating dose regimen of intraperitoneal mitoxantrone: phase I study--clinical and pharmacokinetic evaluation.

Mitoxantrone, a recent anthracenedione derivative, is a potentially useful drug for direct intraperitoneal (i.p.) application because of its high tissue binding and therapeutic index. We have carried out studies to establish maximum tolerated doses as well as pharmacokinetic studies with i.p. mitoxantrone in 21 patients (5 male, 16 female) with gastrointestinal (9), ovarian (6), unknown (2) and other (4) primary cancers and peritoneal carcinomatosis. Increasing doses (10-40 mg/m2) were given i.p. every 4 weeks. Five partial remissions (2-8+ months) and 7 stable disease courses (2-6+ months) were achieved. A reduction or disappearance of ascites was seen in an additional 3 patients. Severe toxicity (leucopenia) was observed in 4 patients only after 35 and 40 mg/m2 i.p. Pharmacokinetic analysis using high performance liquid chromatography yielded the following data: The mean ratio of area under curve peritoneal fluid to plasma was 1109. The peritoneal clearance rate was 680 ml/min and the mean disappearance half life was 13.1 h. Mean urinary excretion within 24 h was 0.42% of the i.p. dose. These data indicate that mitoxantrone is sequestered in the intraperitoneal tissue compartment and only slowly released. Based on the outcome of this phase I study we recommend phase II studies at a dose of 30 mg/m2 i.p., repeated every 3-4 weeks.

Adult↗
PubMed1988

High frequency of graft-versus-host-like syndromes following syngeneic bone marrow transplantation.

Occurrence of acute graft-versus-host reactivity-like (GvHR) syndromes has been shown in at least 3 and possibly in 4 further cases of 9 patients with bone marrow transplants from identical twin donors. The diagnosis of GvHR-like syndromes is based on clinical, immunologic, and histologic features indistinguishable from those observed in graft-versus-host disease (GvHD) grades I-III of patients receiving allogeneic major histocompatibility complex (MHC) matched bone marrow transplants. Induction of GvHR-like symptoms appeared to be correlated with reactivated viral infections after bone marrow transplantation (BMT) or, like in animal models, was due to specific conditioning therapy with cyclophosphamide. The high incidence of acute GvHR-like syndromes in the first months after syngeneic BMT suggests inability of the immune system to discriminate appropriately self from nonself antigens during a normal tolerance induction period after grafting.

Adolescent↗
PubMed1988

[Induction and intensive combined therapy of acute myeloid leukemia in adults].

In a prospective multicenter study the efficacy and toxicity of an induction therapy with daunorubicin, cytosine-arabinoside and VP 16-213, followed by an intensified consolidation with high-dose cytosine-arabinoside and daunorubicin, is evaluated in adult patients with acute myelogenous leukemia. The upper age limit for inclusion in the study was 50 years. Within the first two years of this study 91 patients were enrolled. In 84 patients who have finished the remission induction therapy the rate of complete remissions is 67%. The median survival time of all patients is 22 months and the probability of survival is 46% after 24 months. So far 34 patients in complete remission have been given one or two courses of the intensified consolidation therapy with high-dose cytosine-arabinoside and daunorubicin. The probability of relapse-free survival in these patients is 46% after 22 months and the median remission duration is 20 months.

Adolescent↗
PubMed1988

Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen.

Both mitoxantrone and etoposide have been shown to be active in monotherapy trials of relapsed and refractory acute myelogenous leukemia (AML). This phase II study was undertaken to assess the antitumor activity and toxicity of the combination in refractory and poor-risk AML. The regimen consisted of mitoxantrone, 10 mg/m2/d intravenously (IV), and etoposide, 100 mg/m2/d as short infusion, both on days 1 to 5. Sixty-one patients are evaluable for response and toxicity. Twenty-one were primarily refractory to conventional courses of cytarabine, daunorubicin, and thioguanine; 20 patients had poor-risk first relapse (relapse within 6 months of first complete remission [CR] or relapse under continuous maintenance therapy); 11 had second or subsequent relapses; and nine developed secondary AML after myelodysplastic phase or myelofibrosis. Twenty-six patients (42.6%) attained a CR and seven (11.5%) a partial remission (PR). The median duration of continuous CR was 4.7 months, with a range of 21 days to 14 months, excluding four patients who underwent autologous bone marrow transplantation. Severe myelosuppression was observed in all patients, with a median time to CR of 49 days. Nonhematologic toxicity included stomatitis (mainly grade 1 and 2) in 41 patients, nausea (mainly grade 1 and 2) in 44, infections (mainly grade 3) in 33, and fever of unidentified origin in 11. Other than transient, mild cardiac failure in nine patients, in some of them combined with grade 1 to 2 tachyarrhythmia, no other drug-related cardiac events were observed. Two cases of early death within the first 6 weeks of treatment were registered. Thus, the combination of mitoxantrone and etoposide is a highly active and well-tolerated regimen for refractory and poor-risk AML.

Adolescent↗
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↗
PubMed1987

Stability and pharmacokinetics of m-[131I]iodobenzylguanidine in patients.

A pharmacokinetic study was done to elucidate the body distribution, elimination, and metabolism of m-[131I]iodobenzylguanidine (m-[131I]IBG). For this purpose, an analytical method using solid phase extraction columns was developed. m-[131I]IBG was administered as an i.v. infusion according to different schedules with doses of 7,055 to 13,580 MBq/m2. At the start of the infusion m-[131I]IBG accounted for 93.0 +/- 2.3% (SD; n = 10) of the total radioactivity. At the end of the infusion m-[131I]IBG accounted for 88.0 +/- 7.4%. The non-m-IBG-bound radioactivity was predominantly 131I. The pharmacokinetic parameters (n = 7) are adequately described by a three compartment model. The parameters for m-[131I]IBG were determined with a mean terminal half-life of 37.0 h, a volume of distribution of 307 liters/m2, and an area under the curve value of 1091 kBq x h/ml. The total body clearance was 189 ml/min/m2. The values for 131I showed a terminal half-life of 71.6 h, a volume of distribution of 190 liters/m2, and an area under the curve value of 1537 kBq x h/ml. The total body clearance was 70 ml/min/m2. The selectivity of the m-[131I]IBG treatment might be improved by a reduction of 131I in the infusion fluid and further investigations are warranted.

3-Iodobenzylguanidine↗
PubMed1987

[Anterior wall infarct in an 18-year-old patient with Hodgkin's disease. Possible relation between mediastinal irradiation, accelerated arteriosclerosis and vincristine chemotherapy].

An 18-year-old male patient with Hodgkin's disease, having undergone radiotherapy to the mediastinum two-and-a-half years previously, developed symptoms of an acute myocardial infarction within three hours of a vincristine injection (the first course of vincristine chemotherapy had been finished eight days previously). Invasive investigation after three weeks revealed single-vessel occlusion of the anterior interventricular branch with an anterior-wall aneurysm. The most likely cause of the coronary heart disease in this patient is changes in the anterior interventricular branch resulting from the mediastinal radiotherapy. The infarct itself occurred in close temporal relationship to the vincristine injection, which in several case reports has been implicated in the triggering of coronary spasms.

Adolescent↗
PubMed1987

Comparative in vitro toxicity of mitoxantrone and adriamycin in human granulocyte-macrophage progenitor cells.

Mitoxantrone (MIT) has recently been introduced into cancer therapy as a possible substitute for the structurally related drug, adriamycin (ADR), because it causes less cardiotoxicity and fewer gastrointestinal side effects. However, the dose-limiting toxicity of MIT is pronounced neutropenia. The in vitro hematoxicity of both drugs in granulocyte-macrophage precursor cells (GM-CFCs) was analyzed using drug-exposure schedules analogous to the principles of the in vivo pharmacokinetics of MIT. Bone-marrow and peripheral-blood cells were exposed to 0.075-20 ng/ml MIT or ADR for 5, 20, 60, and 120 min, and for 14 days. The 14-day exposure resulted in Do values of 0.95 and 0.68 ng/ml for bone-marrow and peripheral-blood GM-CFCs subjected to MIT. Exposure to ADR resulted in Do values of 5.43 and 5.13 ng/ml, respectively. As was the case after 14-day exposure to MIT or ADR, short-term exposure again revealed that peripheral-blood GM-CFCs were more sensitive to both drugs. Moreover, at low concentrations, ADR was less toxic than MIT in both types of GM-CFCs, but was more toxic than MIT when a concentration of 20 ng/ml was used. The intracellular concentration of MIT, as measured by high-performance liquid chromatography, was constantly below 1 ng per 2 X 10(7) cells, even when it was applied at a concentration of 20 ng/ml for an exposure time of 2 h. The fact that such low concentrations of MIT are toxic for hemopoietic precursor cells may explain the myelotoxicity of this drug. However, the difference between the precursor-cell toxicity of MIT and that of ADR was small when their respective therapeutic doses were taken into consideration. Further analyses of their toxicity in stem cells and/or the microenvironment would appear to be needed.

Bone Marrow↗
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↗