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Biomedical subjects

W Hinterberger

Publications and source records attributed to W Hinterberger.

At least 109 records · Page 6Linked to original sources

[Allogeneic bone marrow transplantation in acute myeloid leukemia (AML): results in 14 patients].

Between February 1982 and August 1986 14 patients with AML (median age 24 years, range 10-41) underwent allogeneic bone marrow transplantation. 9 patients were grafted in first complete remission, 4 in first relapse, 1 in second relapse and 1 patient with refractory AML. Conditioning consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad). The patients received methotrexate (n = 12) or methotrexate and cyclosporine (n = 2) for prevention of graft versus host disease. Of the 14 patients, 7 are alive, 7 patients died. Causes of death were recurrence of leukaemia (n = 2), veno occlusive disease of the liver (n = 1), CMV-pneumonitis (n = 1), septicaemia (1), cerebral haemorrhage (1), acute graft versus host disease of the gut (1), necrotizing encephalopathy (n = 1). 7 patients are alive between 124 and 1784 days (median 671) in continuous complete remission. All patients but 1 have a Karnofsky-index of more than 80%.

Adolescent↗

[Bone marrow transplantation in chronic myeloid leukemia--experiences in 16 patients].

Between January 1983 and December 1986 16 patients (8 f, 8 m, median age 31.5 years, 14-41) with chronic myelocytic leukaemia (CML) received bone marrow grafts from their HLA compatible sibling donors. 11 patients were in the chronic and 4 in the accelerated phase. 1 patient was in lymphatic blast crisis. The patients were pretreated with busulfan (n = 15, total dose: 100-1000 mg, median: 225), mitobromitol (1 pat.), hydroxyurea (2 pats.), pre-irradiation of the spleen with 800 rad (1 pat.) and one patient had received 3 cycles of vincristin and prednisolone. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad, lung 800 rad). The prophylaxis against graft versus host disease (GVH-D) consisted of methotrexate (MTX) in 14 patients and of MTX in combination with cyclosporin-A in 2. At present (January 15th 1987) 9 patients survive 30 to 1210 days (median 1009) post graft (6/11 grafted in chronic, 2 of 4 in accelerated phase and 1/1 grafted in blast crisis. The causes of death were interstitial pneumonitis (CMV-associated, 2 pats.), venoocclusive disease of the liver (2 pats.), acute GVH-D and septicemia (2 pat.) and relapse (1 pat.). The Karnovsky score of 8/9 survivors is 100%, one patient has a score of 70% due to chronic GVH-D. Bone marrow transplantation for CML bears a high risk of early mortality but offers the unique option of permanent eradication of leukaemic haemopoiesis with subsequent long term survival.

Adolescent↗

[Oral anticoagulant therapy--renaissance of an old therapy?].

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Administration, Oral↗

Survival and quality of life in 23 patients with severe aplastic anemia treated with bone marrow transplantation (BMT).

Survival and quality of life are reported in 23 pretransfused patients with severe aplastic anemia (SAA) who underwent bone marrow transplantation (BMT). The projected survival is 76% with 18 of 23 patients being alive 332 to 1677 days post graft (median: 842). 5 patients died between day 4 and 416. 12 of 17 patients at risk developed chronic graft versus host disease (GVH-D). 4 of these patients have a diminished quality of life due GVH-D related disabling manifestations. Autologous haemopoietic recovery was excluded in all patients by the demonstration of haemopoietic chimerism. We recommand age-adapted rejection prophylaxis; such strategy may help to diminish disabling graft versus host disease in otherwise haematologically reconstituted survivors.

Adolescent↗

Pregnancy and delivery after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). A case report.

A 23 years old multiple pretransfused female with severe aplastic anemia (SAA) underwent bone marrow transplantation (BMT). Cyclophosphamide (200 mg/kg) was used for conditioning, donor buffy coat cells were given as rejection prophylaxis. Seven months after BMT regular menses started in the absence of exogenous hormonal manipulation and 21 months after BMT the patient became pregnant. Pregnancy was complicated by mumps in the 14th week. It was terminated at term by cesarean section. The normally developed newborn girl (3,450 gm) presented with a "persistent fetal circulation syndrome". After surgical correction of the patent ductus arteriosus Botalli the girl baby recovered quickly.

Adult↗

In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders.

Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.

Bone Marrow↗

[Thrombocyte transfusion: increase in platelets in relation to clinical and immunologic prerequisites].

We determined in 35 patients with severe thrombocytopenia (AML n = 10; ALL n = 4; CML = 1; idiopathic myelofibrosis n = 1, aplastic anemia n = 1; undergoing bone-marrow transplantation n = 17) factors influencing the corrected count increment (CCI) after platelet transfusions. Out of 195 transfusions 86 (44%) failed to increased platelet counts (CCI less than 5 X 10(9) platelets/l). A significant percentage of transfusion failures occurred in patients with splenomegaly and/or fever (54% vs. 29%; p less than 0.002). Antibodies directed against donor platelets were found only twice. No correlation between reactivities demonstrable by the lymphocytotoxic test (n = 144) or the radioimmune antiglobulin test (n = 67) and the CCI was obvious. HLA antigen identity was also not predictive. Thus, transfusion failures in patients with low alloimmunization will not be predicted by in vitro antibody screenings. The patients' clinical condition has the most important influence on posttransfusion increment.

Anemia, Aplastic↗

Cytogenetic studies in bone marrow transplant recipients.

Chromosome studies were performed in 24 patients who underwent allogeneic bone marrow transplantation (BMT) for severe aplastic anaemia (8), chronic myeloid leukemia (5 in chronic, 2 in accelerated phase and 1 in lymphoid blast crisis), acute myeloid leukemia (6), acute lymphoblastic leukemia in relapse (1) and Hodgkin's disease (1). Donor-cell type engraftment was demonstrated in 21 patients: in all 17 sex-mismatched transplants and - as demonstrated by reconstitution with Ph-negative cell populations - in 4 CML patients with a sex-matched donor. Recipient-type mitoses were seen in the bone marrow of 5 cases (1 SAA, 3 CML, 1 AML) after transplantation. They were only observed on one occasion in patients with SAA (4 of 25 on day 33) and AML (44 of 50 on day 14). Despite the continued demonstration of some Ph-positive mitoses in 3 patients with CML up to day 28, 323 and 451 after BMT, respectively, all surviving CML patients are still in complete haematological and clinical remission. So far the significance of these cytogenetically abnormal persisting host cells remains unknown.

Adolescent↗

Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other "leukemic" lymphoproliferative disorders.

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM), erythroid committed progenitor cells (BFU-E) and pluripotent hemopoietic progenitor cells (CFU-MIX) in the peripheral blood of patients with hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). In 8 HCL patients retaining their spleens, the number of circulating CFU-GM, BFU-E and CFU-MIX were under the lower limits of normal controls in 6, 6 and 5 cases, respectively, and were in the lower normal ranges in the remaining cases. Six splenectomized HCL patients had generally more circulating progenitor cells than their nonsplenectomized counterparts. In the peripheral blood of 2 patients with ALL and 3 patients with CLL, progenitor cells of all types were markedly increased compared to their respective values in the blood of control subjects. Hairy cells from 2 HCL patients failed to inhibit CFU-GM, BFU-E and CFU-MIX derived colony growth from control peripheral blood mononuclear cells. In 3 HCL patients previously low circulating progenitor cells did not rise 5-7 months after RC-alpha 2-IFN treatment despite normalization of peripheral blood counts. Our results suggest that a reduction of the committed and pluripotent progenitor cell compartment might be at least in part responsible for the pancytopenia in the majority of patients with HCL.

Adult↗

Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone).

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.

Anemia, Aplastic↗

Circulating committed and pluripotent haemopoietic progenitor cells, in infants.

Circulating CFU-GM, BFU-E and CFU-MIX were assayed in 21 infants aged between 1 day and 44 weeks. Compared to 15 adults, progenitor cells of all types were increased until 10 weeks following birth and approached the respective ranges of adults thereafter. The mean increases of progenitor cells in infants aged between 1 day and 10 weeks were 26-fold for CFU-GM, 7-fold for BFU-E and 5-fold for CFU-MIX. Our results demonstrate that not only committed progenitor cells (CFU-GM, BFU-E), but also early progenitor cells with the capacity for self-renewal (CFU-MIX), are increased in early infancy. These data further support the hypothesis that high levels of blood progenitor cells in very early stages of life reflect the colonization process of developing bone marrow by circulating progenitor cells and demonstrate the terminal phase of this process during the first 10 weeks after birth.

Adult↗

[Lineage infidelity of leukemia cells].

We phenotyped 548 blast populations from patients with acute de novo leukemia with a panel of 27 monoclonal antibodies and an antiserum against the enzyme terminal deoxynucleotidyl-transferase (TdT). In 56 cases (10,2%) we found a marker profile consisting of both myeloid and lymphoid characteristics (biphenotypic) leukemia = interlineage infidelity). In 49 out of the 56 cases the blast populations were clearly related to the myeloid (n = 41) or the lymphatic (n = 8) system. In those blast populations only one characteristic of the other differentiation could be detected. However, in 7 cases more than one myeloid as well as lymphatic characteristics were found on the same blast cells. In 4 cases (0.7%) the immunological phenotyping indicated the presence of two separate blast populations. The occurrence of a stem cell leukemia, an abnormal derepression of a genome, a defect of the membrane synthesis and the existence of a normal counterpart are taken into consideration as a cause of an "atypical" marker profile.

Acute Disease↗

Deficiency of fibrinogen and factor VII following treatment of severe aplastic anaemia with anti-thymocyte globulin and high-dose methylprednisolone.

In 4 patients with SAA treated with ATG and high-dose MP, an as yet unrecognized acquired deficiency of fibrinogen and factor VII was observed. The plasma level of fibrinogen fell to 39% (34-51%) and of factor VII:C to 50% (31-55%) of the pretreatment value. The nadirs were between days 10 and 35 (fibrinogen) and d 3 and 11 (factor VII) after the 1st dose of ATG/MP. From additional clotting studies it is concluded that disseminated intravascular coagulation, fibrinolysis, liver cell damage and synthesis of abnormal clotting factors are unlikely causes of these clotting abnormalities. The most probable explanation seems to be a selective inhibition of the synthesis of fibrinogen and factor VII by an as yet unknown mechanism. These clotting abnormalities might, to some extent, increase the bleeding tendency in these patients, which up to now had been solely attributed to thrombocytopenia.

Adult↗