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Biomedical subjects

P Bettelheim

Publications and source records attributed to P Bettelheim.

At least 109 records · Page 6Linked to original sources
PubMed1985

[Cooperative studies in the treatment of acute lymphoblastic leukemia in children in Austria--report of 10 years' experience].

437 children with acute lymphoblastic leukaemia (ALL) have been treated at 9 different institutions in Austria utilizing common protocols and central registration between 1974 and 1984. 227 patients (132 boys and 95 girls, group I) were treated between 1974 and 1980 using 3 consecutive protocols (KMK, O 76, A 78), which were essentially derived from the Memphis studies VII and VIII. Patients with a high risk of relapse were treated according to the LSA 2-L2 protocol. 210 patients (112 boys and 98 girls, group II) were consecutively treated following the BFM protocols 76/79 and 81/83. In this group, treatment intensity was adjusted to the initially determined individual risk of relapse (BFM risk score or risk factor). To date, the life table analysis demonstrates that the probability of continuous complete remission for patients in group II is 60% after 5 and 3 years (BFM 76/79 and BFM 81/83, respectively), whereas group I reaches a level of 37.3%. The prognostic difference between risk and non-risk patients in both studies of group II was eliminated. Despite a higher morbidity and non-leukaemia-related mortality in group II, the therapeutic success can be attributed to the intensification of induction therapy.

Asparaginase↗
PubMed1985

Unexpected absence of a myeloid surface antigen (3-fucosyl-N-acetyllactosamine) in promyelocytic leukemia.

According to the criteria of the FAB classification we diagnosed acute promyelocytic leukemia in 19 out of 191 AML blast cell populations. The reaction pattern with the anti-myeloid monoclonal antibodies VIM2, MCS2 and MY9 and the MHC-class II antibody VID1 in all cases showed the characteristics which were expected from the normal granulopoiesis. The monoclonal antibody VIM-D5, which recognizes the myeloid cell surface structure 3-fucosyl-N-acetyllactosamine (3-FAL), was not reactive with the majority of promyelocytic blast cells, however. In 13 cases 3-FAL was not detectable and in 6 cases only low or moderate reactivity of VIM-D5 with blast cells was observed. The phenotype of leukemic promyelocytes thus differs from the majority of normal promyelocytes in this respect.

Antibodies, Monoclonal↗
PubMed1985

Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia.

Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast-populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile. In contrast to acute myeloid leukaemia (AML), we found frequent involvement of the thrombopoietic and erythropoietic systems in myeloid CML-BC. Furthermore, the marker profile on blast cells in myeloid CML-BC was different from that seen in AML. The blast cells in lymphoid blast crises of CML displayed the same lymphoid marker profile as those in acute lymphoblastic leukaemia. In three of 16 patients who were serially tested, we observed phenotypic changes in the blast cell populations. In one patient the blasts changed from lymphoid to myeloid type while remaining TdT-positive; in another case the blasts switched from granulomonocytic TdT-negative to granulomonocytic TdT-positive. In the third patient erythroid precursor cells appeared as the disease progressed. The results indicate the capacity of blast populations in CML-patients during blast crisis to differentiate along several pathways.

Adolescent↗
PubMed1985

Deficiency of the autologous mixed lymphocyte reaction in patients with classic hemophilia treated with commercial factor VIII concentrate. Correlation with T cell subset distribution, antibodies to lymphadenopathy-associated or human T lymphotropic virus, and analysis of the cellular basis of the deficiency.

14 patients with hemophilia were studied for the distribution of T cell subsets, the presence of antibody to lymphadenopathy-associated or human T lymphotropic virus type III (LAV/HTLV-III), and their responsiveness in autologous mixed lymphocyte reactions. In addition, mitogen and alloantigen responsiveness and Interleukin-2 production were investigated. Seven patients were found to have low Leu 3a/Leu 2a (T4/T8) ratios; eight patients had antibody to LAV/HTLV-III; and an additional patient had acquired immunodeficiency syndrome. Responsiveness to mitogens and alloantigens as well as Interleukin-2 production were comparable with those of healthy individuals. However, patients with low ratio, many of whom had antibodies to LAV/HTLV-III, had a highly deficient autologous mixed lymphocyte reaction. This reduced response of T cells to autologous non-T cells could not be corrected by elimination of Leu 2a/T8 cells, which indicated that there was a preferential loss of the Leu 3a cell subset(s) which responded to autologous non-T cells. Thus, these patients have a deficiency of intercellular communication within their immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1985

5q- chromosome in acute leukemia with lymphoid morphology and expression of myeloid membrane determinants.

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping exhibited a pure myeloid in one patient and a biphenotypic membrane marker profile in the other two patients. Cytogenetic studies revealed a 5q- chromosome as a common marker and additional individual changes. Two of the patients who were treated according to acute lymphoblastic leukemia (ALL) therapy protocols died without remission five and four weeks after diagnosis, respectively. Despite relapsing several times, another patient survived for over eight years. These three patients seem to represent one new subgroup of leukemias that can only be distinguished from typical ALL by both determination of cell surface markers and cytogenetic analysis.

Aged↗
PubMed1985

5q - marker chromosome in acute leukemia with lymphoid morphology and myeloid differentiation antigens.

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping showed a pure myeloid in one and a biphenotypic (mixed lymphoid/myeloid) membrane marker profile in two of the patients. Cytogenetic studies revealed a 5q - chromosome as a common marker with additional individual changes. Two of the patients who were treated according to ALL-therapy protocols died without remission 5 and 4 weeks after diagnosis, respectively. Despite relapsing several times, the third patient survived for over 8 years. These three patients seem to represent one new subgroup of leukemias which can only be distinguished from typical ALL by determination of both cell surface markers and cytogenetic analysis.

Aged↗
PubMed1985

[Blood protein concentrations--are they parameters of disease activity in Crohn's disease?].

Concentrations of 19 different proteins were measured after hospital admission, before hospital discharge and 3 months thereafter in 40 patients suffering from an acute episode of Crohn's disease. Serum levels of acute phase proteins (alpha 1-glycoprotein, alpha 1-antichymotrypsin, alpha 1-antitrypsin, CRP, haptoglobin) and immunoglobulin M corresponded to the severity of inflammatory symptoms and correlated significantly with CDAI (Crohn's disease activity index). Albumin and transferrin were characteristic for nutritional status of the patient under basal conditions and during nutritional therapy. Prealbumin and retinol-binding protein behaved similarly, but results were not significant. The measurement of the proteins mentioned give valuable clues in regard to the course of the disease and therapeutic success in Crohn's disease.

Adolescent↗
PubMed1984

M2, a novel myelomonocytic cell surface antigen and its distribution on leukemic cells.

The selectivity of a novel myelomonocytic cell surface antigen, designated M2, has been assessed in a series of 208 leukemias. The M2 antigen is defined by a monoclonal antibody (VIM-2) of the IgM class. Its expression within the normal hemopoietic system is restricted to myelomonocytic cells. Lymphocytes, erythrocytes, thrombocytes and their morphologically recognizable precursors are negative. Sixty of the 66 acute myeloblastic leukemias (= 91%) and 28 of the 30 myeloid blast crises of CML patients (= 93%) were M2-positive. As expected from our findings with normal myeloid cells, the myeloid cells found in stable phase of CML were also in all instances, M2-positive. Quite in contrast, lymphoid cells from patients with B-CLL, T-CLL, prolymphocytic leukemia, hairy-cell leukemia, lymphoblastic lymphoma, Sézary syndrome, from CML patients in lymphoid blast crisis and from the majority of patients with ALL, were completely M2-negative. Also negative were the blast cells of patients with acute megakaryoblastic leukemia and acute erythroleukemia. A direct comparison of M2 expression with the display of the 3-fucosyl-N-acetyllactosamine determinant, the structure recognized by most of the anti-myeloid monoclonal antibodies reported so far, shows that more AMLs are M2-positive and the proportion of M2-positive blast cells in individual AML samples is higher.

Antibodies, Monoclonal↗
PubMed1984

Malignant histiocytosis with unusual features. Disseminated intravascular coagulation with severe hyperfibrinolysis, acute polyneuroradiculitis Guillain-Barré, and a unique chromosome abnormality.

The case of a 25-year-old man with the characteristic features of malignant histiocytosis (proliferation of abnormal histiocytic cells with erythrophagocytosis, hepatosplenomegaly, increased serum acid phosphatase, hypercalcemia, and bone pain) is reported. Chromosome studies revealed a near tetraploid karyotype with a pair of marker chromosomes. A few hours after initiation of chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisolone (CHOP regimen), the patient developed an acute ascending paralysis. Cerebrospinal fluid (CSF) findings were consistent with a diagnosis of Guillain-Barré Syndrome. On the next day, disseminated intravascular coagulation (DIC) with severe hyperfibrinolysis occurred. After intensive chemotherapy, complete remission could be achieved.

Adult↗
PubMed1984

Efficacy of the M-2 protocol in previously untreated patients with advanced multiple myeloma.

37 consecutive, previously untreated patients with advanced multiple myeloma (16 patients Stage II, 21 patients Stage III) were treated with a five drug regimen consisting of carmustine, melphalan, vincristine, cyclophosphamide and prednisolone (M-2-protocol) in a prospective manner. Remission was achieved in 24 patients (65%). The median time to remission was 10 weeks, the median duration of remission 15,3 months. Median survival time from the onset of treatment was 24 months for all patients. Responding patients have a projected 65% three year survival. Median survival in non-responders was 10 months. 8 patients died during the first year of treatment. These results do not confirm the favourable results with this drug combination obtained in a previous trial. The discrepancy may be explained by a higher proportion of poor risk patients in the present study.

Aged↗
PubMed1984

Monoclonal antibodies to human myelomonocyte differentiation antigens in the diagnosis of acute myeloid leukemia.

The immunological definition of malignant lymphatic cells has already been routinely applied by many laboratories over a number of years. Today it is clear and undisputed that the phenotypic data obtained in that way are often very useful and supporting. The immunological definition of non-lymphoid leukemias is not yet as far advanced. Additional surface markers for the recognition of poorly differentiated non-lymphoid cells are clearly needed. In this paper ten monoclonal antibodies to myeloid surface antigens are described. It is hoped that they are a useful addition to the presently available relatively small panel of well studied myeloid surface markers which are displayed by immature malignant blast cells.

Antibodies, Monoclonal↗
PubMed1984

Diagnostic specificity of the monoclonal anti-CALLA antibody VIL-A1 in leukemia and malignant lymphoma.

VIL-A1 is an anti-CALLA antibody which binds efficiently and exclusively to CALLA positive cells. When the cell type specificity of VIL-A1 is studied in acute leukemias and lymphomas, results show that in those leukemias which could be characterized by cytochemical and morphological methods, VIL-A1 reactivity was specific for cells of lymphoid origin. It can therefore be assumed that VIL-A1 positive AUL cells (in this case 4 out of 9 patients) are also lymphoid in origin. In no case were AML blasts found to be positive with this antibody. Seventy-four per cent of the 88 ALL patients were positive (L1 + L2) whereas none in the L3 subgroup were positive, and 48% of CML patients in blastic crisis were positive. Of the low grade non-Hodgkin malignancies, only CB/CC was positive, distinguishing it from the CC type which was negative. Of the high grade lymphomas IB was found to be negative, while the others showed a heterogeneous picture which was not related to other immunological parameters.

Acute Disease↗
PubMed1984

Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells.

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Animals↗
PubMed1984

Range and clinical significance of the number of myeloid-committed stem cells in the blood of patients with acute leukaemia in remission.

Circulating granulocyte/macrophage progenitor cells (CFU-GM) were assayed serially during remission in 17 patients with acute leukaemia (9 ALL, 8 AML). In patients with ALL receiving cyclophosphamide, 6-mercaptopurine and methotrexate, CFU-GM numbers were significantly lower than in normal individuals; cycles of 'reinduction' chemotherapy (vincristine, prednisolone) caused a 10-fold increase in CFU-GM per ml of blood. In 2 ALL patients a substantial increase in CFU-GM numbers preceded the morphologically detectable relapse. In patients with AML receiving repeated courses of cytosine-arabinoside and 6-mercaptopurine, circulating CFU-GM were likewise reduced. In 6 patients who relapsed, a further reduction of CFU-GM was seen. A complete absence of circulating CFU-GM was observed in 10 of the 23 investigations performed within 6 weeks prior to the morphologically detectable relapse, while such a 'zero'-growth occurred in only 1 of 54 experiments performed during stable remission. In summary, in patients with ALL in remission, circulating CFU-GM are increased following treatment with vincristine and prednisolone. In patients with AML, declining numbers of circulating CFU-GM may predict an imminent relapse.

Acute Disease↗
PubMed1983

Glycosylated hemoglobin as a long-term parameter in appraising the severity of hemolytic disease.

Reduced levels of glycosylated hemoglobins (GHb) have been found to be closely related to red cell survival. We therefore studied the relation of this parameter to the clinical applicability in patients with hemolytic disease (n = 20). During a 5-week period we repeatedly measured severity of anemia, i.e., hemoglobin (Hb), packed red cell volume (VPRC), and red blood cell count (RBC), as well as reticulocytosis and parameters of red cell destruction such as serum concentration of lactic dehydrogenase (LDH) and bilirubin together with GHb. There was a weak correlation between simultaneously measured GHb and RBC (r = 0.5, P = 0.02), but none was demonstrable between GHb and Hb, VPRC, reticulocyte counts, LDH, or bilirubin. A much closer correlation, however, was found between actual GHb levels and RBC determined 3-5 weeks previously (r = 0.72, P = 0.001), as well as Hb (r = 0.56, P = 0.015), VPRC (r = 0.57, P = 0.013), reticulocyte counts (r = -0.63, P = 0.006), LDH ( r = -0.53, P = 0.02), and serum bilirubin concentrations ( r = -0.55, P = 0.016). Ghb was also significantly decreased in patients with consistently low values of reticulocytes when red cell destruction was demonstrable. These results show that GHb is a measure of red cell destruction and restitution, and thus may be usefull for long-term monitoring of patients with hemolytic disease.

Adolescent↗
PubMed1983

T-cell alterations in hemophiliacs treated with commercial clotting factor concentrates.

Various immunological parameters were determined in 46 patients with severe hemophilia A and in 9 patients with severe hemophilia B. All patients were treated over many years with commercial factor VIII or IX concentrates. Patients with severe classic hemophilia had a significantly reduced relative and absolute number of T-helper cells and a significantly increased relative and absolute number of T-suppressor cells. About half of these patients had an inverse T-helper/suppressor cell ratio. Patients with moderate hemophilia A and severe hemophilia B did not show these abnormalities. Hemophiliacs with an inverse ratio had a significantly higher concentration of serum total protein, IgG and IgM. No relationship between the amount of factor VIII concentrate administered, the HLA-type of the patient, the presence or absence of CMV-antibodies, hepatitis markers, thrombocytopenia and abnormal liver function tests to the T-cell abnormalities could be established. Lymphadenopathy was frequently associated with an inverse ratio. Indirect evidence suggests that the alterations of the immune system began in 1979/80.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Glycophorin A expression in malignant hematopoiesis.

Two hundred twenty-nine patients with hematopoietic malignancies were tested for reactivity with a monoclonal anti-human glycophorin A antibody. One hundred twenty-three of these cases were classified as acute leukemias of either the myeloid, lymphoid, erythroid, or undifferentiated type. The monoclonal antibody we used (VIE-G4) was obtained after immunization with a human thymocyte suspension. It selectively reacts with glycophorin A (GpA) and strongly binds to 40% of K-562 cells and all morphologically recognizable erythroid precursor cells. Apart from two cases with acute erythroid leukemia, this antibody reacted with none of the malignant cells in the 229 tested hematopoietic malignancies, including the 121 nonerythroid acute leukemias. This finding seems to contradict the earlier observations by L. Andersson and colleagues that a considerable proportion of acute leukemias express GpA on their surface. One reason for this discrepancy might be the fact that VIE-G4 detects only complete glycosylated GpA. If this is the sole explanation, this would mean that the poorly differentiated cells in these cases express incompletely glycosylated GpA.

Acute Disease↗