Search PubMed⌕ Search

Biomedical subjects

W Hinterberger

Publications and source records attributed to W Hinterberger.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Autologous bone marrow transplantation in intestinal carcinoma].

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Bone Marrow Transplantation↗
PubMed1995

[Possible role of autotransplantation in small cel bronchial carcinoma].

Autologous bone marrow transplantation (ABMT) performed with recent achievements plays yet no established role in the treatment of small cell lung cancer (SCLC). The majority of treatment results obtained so far do not clearly suggest a superiority of high-dose therapy with autologous transplantation over conventional polychemo/radiotherapy. It is unknown, whether or not a subgroup of patients with, e.g., "limited disease" and chemosensitive tumor may benefit from ABMT. Randomized trials will be necessary to clarify this question.

Bone Marrow Transplantation↗
PubMed1994

Coincidence of severe aplastic anaemia with multiple sclerosis or thyroid disorders. Report of 5 cases.

Five patients with severe aplastic anaemia (SAA) who, simultaneously (n = 3) or consecutively (n = 2), presented with multiple sclerosis (MS) (n = 2) or immune hyperthyroidism (IHT) (n = 2) or subacute thyroiditis (n = 1) are described. Two female patients with MS developed SAA after a small dose of azathioprine. Another patient simultaneously presented with IHT and SAA. SAA and MS responded to cyclosporine while IHT required 131I. Relapsing SAA in 1 patient with MS was treated with antithymocyte globulin (ATG) which induced acute exacerbation of MS. Despite the low total dose of ATG (31.5 mg/kg), complete remission of SAA was obtained. Two other patients developed thyroid disorders, 42 and 106 months after successful immunosuppression with ATG/high-dose methylprednisolone. IHT and subacute thyroiditis were successfully treated with 131I or prednisolone, respectively, without recurrence of SAA in both cases. These are the first documented cases of SAA evolving in the course of MS while the coincidence with IHT was already described. Since enhanced expression of interferon-gamma plays a crucial role in SAA as well as in MS and in IHT, similar pathogenetic principles may apply for these seemingly unrelated disorders.

Adult↗
PubMed1994

[The value of sequential CD 34 measurement for carrying out stem cell pheresis].

The recent significant improvement in disease-free survival in patients with certain haematological malignancies is due to high-dose chemotherapy and subsequent autologous bone marrow and/or stem cell transplantation. The proliferation and egression of stem cells into the peripheral blood must first be stimulated by defined chemotherapy and/or by administration of cytokines. However, the increase of circulating stem cells in peripheral blood is limited to only a few days. By immunologically analysing white blood cells for the expression of the surface antigen CD 34 it is possible to calculate the numbers of haematopoietic progenitor cells. Thus, besides monitoring haematopoietic recovery, the estimation of CD34+ cells in the peripheral blood can be used to indicate the optimal time point for stem cell collection. Two to four stem cell pheresis (one per day) may then yield sufficient stem cells to enable the safe and rapid reconstitution of haematopoiesis following supralethal chemotherapy.

Antigens, CD↗
PubMed1994

Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group.

Six hundred and eighteen patients with acquired aplastic anaemia grafted from an HLA-identical sibling donor between 1976 and 1990 in eight European centres were reported to the Working Party for Severe Aplastic Anaemia (SAA) Registry and were evaluable for analysis of the incidence of graft failure/rejection and the outcome of second bone marrow transplants (BMT). The number of patients experiencing graft rejection declined significantly over the study period from 32% to 8% (p < 0.0001). This coincided with the introduction of cyclosporine to the conditioning regimen for BMT. The graft rejection rate in the post-hepatitis SAA group was significantly lower than in the group with idiopathic SAA (4% vs 20%) (p = 0.001). The use of irradiation in the conditioning regimen significantly reduced the number of patients experiencing graft rejection (7% vs 21%) (p = 0.004). Age, sex and severity of disease did not influence the rate of sustained engraftment. Of the 85 patients experiencing graft rejection, 41 received a second transplant: their survival is 33% vs 8% for patients not transplanted a second time (p = 0.003). The major factor predicting the outcome of second BMT for SAA was the interval from first BMT. Patients receiving a second BMT within 60 days from the first BMT had a significantly poorer outcome.

Adolescent↗
PubMed1993

Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party.

This study was designed to determine the incidence of relapse and factors predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after immunosuppressive treatment (IS). Patients developing myelodysplasia or acute leukaemia after IS, and patients receiving a transplant, were excluded from this analysis. Response was defined as reaching complete independence from transfusions, relapse was defined as becoming again transfusion dependent. This criteria was validated by similar figures when using other 'relapse criteria' such as drop in neutrophil or platelet counts. Of 358 patients responding to IS. 74 patients relapsed after a mean time of 778 d after treatment. The actuarial incidence of relapse is 35.2% at 14 years after IS. The risk for relapse was higher in patients responding within 120 d from IS (48%) compared to patients responding between 120 and 360 d (40%) and only 20% for slow responders (> 360 d from IS) (P < 0.00001). In multivariate analysis this factor still proved significant (P < 0.0001). The mean time between diagnosis and treatment was significantly longer in patients relapsing compared to patients who did not relapse (260 v 134 d, P = 0.037). Relapse was not predicted by the severity of the disease, age, and sex. In 39 of the 74 relapsing patients a second response could be achieved. Responses after relapse were associated in univariate analysis with early response to previous IS and early occurrence of relapse. The actuarial survival of patients not relapsing is significantly better than survival of patients relapsing (79.8% v 67.1%, P = 0.0024). However, the actuarial survival of 39 relapsing patients who responded again to IS was similar to patients not relapsing (86%) and significantly better than in 35 patients not reaching a second response after relapse (49.3%, P = 0.0015). This study indicates that relapse is a relevant problem in the treatment of aplastic anaemia, and does have an impact on overall survival. Prospective studies of immunosuppressive regimens, looking at responses, should also address this problem in the future.

Adolescent↗
PubMed1993

[Collection and long-term preservation of peripheral stem cells].

The methods of collection and storage of peripheral blood stem cells are described and the harvesting after conditioning with cytokines and/or myelosuppressive therapy is discussed. It could be demonstrated that the combination of cytostatics and cytokines gives the best yield and enables to collect a sufficient amount of peripheral blood stem cells for a successful engraftment after myeloablative therapy with only few aphereses.

Antigens, CD↗
PubMed1993

Anabolic steroids and blood cell production.

In the past anabolic steroids were the first-choice treatment for pancytopenic disorders that were often poorly classified. They are now superseded by other more recently developed methods of treatment--for example bone marrow transplantation and immunosuppression. This contrasts to the authors' experience, and to that of many other haematologists, who have noted anabolic steroid-induced responses in patients who were unsuitable for or unresponsive to the new treatments. Anabolic steroids did not, however, demonstrate an obvious effect in recent controlled trials involving patients with aplastic anaemia. Their use with immunosuppressive treatment is currently under investigation. Although anabolic steroids rarely reverse the course of anaemia in a myelodysplastic syndrome, even a slight haemopoietic improvement is desirable. Children with Fanconi's anaemia may benefit from a reduced transfusion requirement. Uraemic patients may experience significant side effects on standard erythropoietin (epo) treatment. There have been no controlled trials comparing epo versus anabolic steroids or epo versus epo in conjunction with anabolic steroids. Data from uncontrolled studies indicate a better response to anabolic steroids in children and females than in men. In spite of the fact that anabolic steroids have been used for almost 30 years, they should be carefully re-evaluated in scientifically controlled trials to test their efficacy and to compare them with the new treatments. Such trials, however, are impeded by the limited knowledge available with regard to pharmacological parameters and optimal treatment schedules.

Anabolic Agents↗
PubMed1992

In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 on thrombopoiesis in primates.

Using a primate model, we examined the effect of recombinant human interleukin-3 (rhIL-3) and rhIL-6 on thrombopoiesis in vivo. Administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days increased levels of circulating colony-forming units megakaryocyte (CFU-Mk) by approximately 15-fold in five rhesus monkeys without raising their platelet counts. In contrast, administration of 30 micrograms/kg/d of rhIL-6 for 10 days in four animals did not increase CFU-Mk levels but significantly raised platelet counts from a mean pretreatment value of 460 x 10(3)/microL (range 360 to 610) to a mean maximum of 746 x 10(3)/microL (665 to 790) on day 8. If monkeys were pretreated with rhIL-3 (33 or 100 micrograms/kg/d for 11 days) to expand their CFU-Mk compartment, the thrombopoietic effect of rhIL-6 was synergistically enhanced leading to platelet counts above 1,000 x 10(3)/microL (mean maximum value 1,247) in all three primates studied. The sequential administration of rhIL-3 and rhIL-6 might represent a powerful strategy to stimulate thrombopoiesis in vivo.

Animals↗
PubMed1992

Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady-state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator.

Bone Marrow Transplantation↗
PubMed1992

Detection of circulating endogenous interleukin-3 in extensive chronic graft-versus-host disease.

Recent data suggest that activated immune cells and their products are involved in the initiation and progression of graft-versus-host disease (GVHD). To test whether the production of endogenous interleukin-3 (IL-3), a product of activated immune cells, might be an indicator of disease activity in GVHD, we analysed sera of 61 bone marrow transplant (BMT) recipients for IL-3 levels by using an enzyme linked immunosorbent assay. Measurable levels (greater than 25 pg/ml) of endogenous IL-3 were detected in a significant subgroup (5/16 patients, 31.25%) of allograft recipients suffering from extensive chronic GVHD, but not in patients with limited chronic GVHD (n = 6) or in those without signs of chronic GVHD (n = 17). In IL-3 positive patients, IL-3 levels were not associated with pathologic conditions (such as infectious disease) other than GVHD. IL-3 levels were undetectable in disease-free phases preceding severe chronic GVHD. Lower levels of IL-3 were measured in chronic GVHD patients during extensive disease while on high dose steroid medication compared with before and/or after (p less than 0.02). IL-3 was also detected in a small group (2/17) of patients suffering from acute GVHD. IL-3 could neither be detected in syngeneic (n = 3) nor autologous (n = 7) BMT recipients nor in the vast majority (99/100) of healthy controls. Together, measurable amounts of IL-3 are produced in a significant subgroup of patients suffering from extensive chronic GVHD.

Adolescent↗
PubMed1991

Ratio of complement receptor over Fc-receptor III expression: a sensitive parameter to monitor granulocyte-macrophage colony-stimulating factor effects on neutrophils.

In vitro activation of human granulocytes leads to altered expression of distinct surface antigens. Compared with the changes observed with classic activating reagents such as the phorbol ester PMA similar, but less pronounced alterations of surface antigen expression were observed upon granulocyte activation with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF). In particular, stimulation with hrGM-CSF is followed by an enhanced expression of the complement receptors CD35 (CR1) and CD11b (CR3) while the low affinity Fc-gamma receptor CD16 (FcRIII) is downregulated. In order to investigate whether there are similar effects under in vivo conditions, we studied the granulocytes from patients undergoing rhGM-CSF therapy before, during, and after treatment. We found a marked increase in CD35 (CR1) and CD11b (CR3) expression and a substantial decrease or even loss of CD16 (FcRIII) on these granulocytes. These changes correlated well with our in vitro data and occurred extremely rapidly after therapy onset. Furthermore, therapy monitoring using ratios calculated by the mean fluorescence channel numbers of CR and FcRIII stainings may combine the advantage of high sensitivity with high reproducibility as a result of the contrasting change in CR and FcRIII expression during granulocyte activation. Being nonparametric values, such ratios are not influenced by individual flow cytometry standardization. Taken together, these activation-associated changes of surface receptor expression and especially of CR over FcRIII ratios are useful parameters for monitoring the in vivo effects of rhGM-CSF.

Antigens, CD↗
PubMed1991

Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia.

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

Adult↗
PubMed1991

Detection of engraftment and mixed chimerism following bone marrow transplantation using PCR amplification of a highly variable region-variable number of tandem repeats (VNTR) in the von Willebrand factor gene.

Detection of host cells in peripheral blood and/or bone marrow (mixed chimerism) of patients who have undergone bone marrow transplantation (BMT) is possible using either immunological methods or cytogenetic or molecular genetic analysis. We shall report a new method for the detection of mixed chimerism, which makes use of the fact, that the von Willebrand factor (vWF) gene has a highly variable region-variable number of tandem repeats (VNTR)--within intron 40. vWF-VNTR amplification by the polymerase chain reaction (PCR) was performed as described by Peake et al. We have studied 185 peripheral blood and/or bone marrow samples of 26 patients. Median time after BMT was 14 months (range 1-83 months). Of the 11 patients who were studied sequentially during the first 100 days following BMT, mixed chimerism was detected in four, but only transiently. None of these patients has relapsed so far. Of 18 patients who were studied more than 100 days after BMT mixed chimerism was found in three; two of these patients have subsequently relapsed. The advantages of this new method are: (a) it is informative in a high percentage of patients; (b) it requires only small amounts (200 microliters) of peripheral blood; (c) reliable results can be obtained at leukocyte counts of even less than 50 per microliters. The clinical relevance and sensitivity of the method compared with established methods for detection of mixed chimerism remain to be determined.

Bone Marrow↗
PubMed1991

[Autologous bone marrow transplantation in children with acute leukemia or non-Hodgkin's lymphoma].

More than 95% of children with acute lymphoblastic leukemia (ALL) achieve complete remission with conventional chemotherapy and 60 to 70% are cured. In contrast, only 70 to 80% of children with acute myeloid leukemia (AML) achieve remission and 30 to 40% are cured. In acute leukemia, ALL and AML, high initial white blood cell counts, poor initial response to therapy, certain structural chromosomal abnormalities, and diagnosis under 1 year of age indicate an increased risk of relapse. Prognosis is poor in children, who relapse during treatment. If no bone marrow donor is available, high dose chemo(radio)therapy and autologous stem cell rescue can be applied in these children to consolidate second remission. Furthermore, autologous bone marrow transplantation may be used to consolidate first remission of individual children, who suffer from acute leukemia with high risk criteria. 19 children with a median age of 8 years (0.5 to 19 years) underwent high dose chemo(radio)therapy and autologous bone marrow and/or blood derived stem cell rescue. 11 suffered from ALL, 4 had AML, and 4 suffered from Non Hodgkin's lymphoma (NHL). 7/13 children (54%), who were in first or second remission after early relapse, are alive in continued remission for median 24 months (9 to 44) after autografting. Children in more advanced stage of disease had no benefit from high dose therapy and autologous stem cell rescue.

Adolescent↗
PubMed1991

[Chronic myeloid leukemia].

Chronic myelocytic leukemia is a malignant clonal disorder which, after a chronic phase of about 3 to 4 years, progresses to blastic transformation. The disease is incurable by conventional cytostatic treatment. Once blastic transformation has ensued, survival is limited to weeks or months. Interferon may prolong the chronic phase, but data are controversial. Allogeneic bone marrow transplantation may cure 40 to 70% of patients treated while in chronic phase. Survival is about 20% in advanced disease, depending mainly on age, sex of donor and clinical condition. Allogenic bone marrow transplantation was hitherto restricted to patients having an HLA-identical bone marrow donor. Volunteer bone marrow donor registries now contain about 400,000 registered unrelated healthy donors: The chance of finding an unrelated bone marrow donor is now between 10 and 60%, and the chance will increase when donor registries expand.

Antineoplastic Agents↗