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C Aul

Publications and source records attributed to C Aul.

At least 127 records · Page 7Linked to original sources
PubMed1992

T-cell receptor gamma/delta expressing acute leukemia emerging from sideroblastic anemia: morphological, immunological, and cytogenetic features.

Striking numerical and structural chromosome abnormalities (-Y, +8, i(7q), del (10)(q24), and del (11)(q21)) were detected by cytogenetic analysis in a patient's bone marrow with morphological features of both acute lymphoblastic leukemia and myelodysplastic disorder. Surface marker analysis characterized blast cells to be CD2+ CD7+ CD3+ CD4- CD8- expressing gamma/delta-T-cell receptor antigen and coexpressing CD11b and CD16. Exhibiting an identical phenotype as the leukemic cells, a prominent gamma/delta-TCR+ lymphocyte population was found in the bone marrow as well as in the peripheral blood. Cells of the latter compartment coexpressed CD56 and HLA-DR antigens and exhibited nonspecific cytotoxic activity. In the bone marrow cells NSCA could be induced after stimulation with interleukin 2 in vitro. Morphological, immunological, and cytogenetic findings suggest that gamma/delta-T-ALL emerged from a myelodysplastic disorder after sequential steps of malignant transformation. Leukemic cells with "mixed lineage" character may provide evidence for a common progenitor cell in the bone marrow. Assuming that the leukemic cells represent the malignant counterpart of normal CD3+ gamma/delta-TCR+ cells the results may contribute to our understanding of the origin and differentiation as well as the possible steps of malignant transformation of a gamma/delta-TCR+ lymphocyte population.

Anemia, Sideroblastic↗
PubMed1992

Age-related incidence and other epidemiological aspects of myelodysplastic syndromes.

Although most haematologists perceive a rising prevalence and incidence of myelodysplastic syndromes (MDS), reliable epidemiological data on these disorders are largely lacking. The bone marrow register of the University of Düsseldorf allowed us to assess among other epidemiological features the incidence of MDS, which was compared to that of acute myeloid leukaemia (AML). Among a total of 18,416 different patients registered between 1975 and 1990, 584 cases of MDS (3.2%) and 506 cases of AML (2.8%) were identified. Over the study period, the percentage of newly diagnosed MDS rose from 1.3% to 4.5%, while there was no upward trend for AML. Among all patients undergoing bone marrow biopsy, the proportion of those over 60 years of age increased from 41.9% in 1975 to 54.1% in 1990. We found a strong correlation between the proportion of elderly patients and the relative frequency of MDS diagnoses. Thirty-one patients (5.3%) were classified as a secondary MDS because of previous treatment with cytotoxic chemotherapy and/or irradiation for a variety of malignancies. Twelve patients were identified in whom occupational exposure to organic solvents could not be ruled out. For calculating age-specific incidence rates, the analysis was confined to the town district of Düsseldorf (575,000 inhabitants), because exact demographical data were available for this population. In the last quinquennium of the study period (1986-90), myelodysplastic syndromes were more frequent than AML in the age group 50-70 years (4.9 v 1.8/100,000/year). In patients over 70, the incidence of MDS was more than 3 times that of AML (22.8 v 6.7/100,000). In this group, men had a higher incidence of MDS (33.9/100,000) than women (18/100,000). Crude annual incidence (all age groups) was also higher for MDS (4.1/100,000) than for AML (2.1/100,000) in recent years. We conclude that MDS are relatively common haematological neoplasias. The rising incidence in recent years is probably not due to changes in aetiological factors, but may reflect increased awareness on the part of physicians and extended use of diagnostic procedures in elderly patients.

Acute Disease↗
PubMed1992

[Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes].

In a retrospective analysis we assessed the data of 46 patients with myelodysplastic syndromes (MDS), who had received more than 50 blood transfusions during the course of disease. The number of units given ranged from 50 to 155 (mean 79). 20 patients (RA n = 4, RARS n = 12, RAEB n = 1, RAEB/T n = 2, CMML n = 1), followed up between 8 and 108 months (mean survival time 39.4 months), developed a secondary hemochromatosis. More than 40% of the patients showed signs of heart failure, in some cases accompanied by cardiac arrhythmias. 11 patients also suffered from hepatopathy and 5 developed diabetes mellitus. Secondary hemochromatosis was particularly common in patients with RARS. Refractory congestive heart failure secondary to hemochromatosis was the cause of death in 14 patients, whereas none died from hepatic insufficiency. We conclude that the risk of secondary hemochromatosis should not be neglected in polytransfused patients with MDS. In some cases, particularly those with favorable prognostic features of MDS, it may shorten life expectancy. The availability of a new oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one or L1) offers a promising and practicable approach to prevent this complication.

Adult↗
PubMed1992

Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic progenitor cells.

Gradual increase of CD38 on cells expressing CD34 characterizes the early cell differentiation pathway of normal human hematopoietic progenitors. In this study the coordinated expression pattern of CD34 and CD38 was assessed on leukemic blasts from bone marrow aspirates of 95 patients with newly diagnosed acute myeloid leukemia (AML). Expression was divided into six categories analogous to the differentiation pathway of normal bone marrow. The CD38 antigen was expressed on the leukemic cells of all patients and CD34+ leukemic cells were found in 79 patients (83%). In 93 patients, the leukemic cells were found along the differentiation pathway defined by CD34 and CD38. In 33 of the 93 patients, a part of the CD34+ cells did not express the CD38 antigen (categories 1 and 2). In another 33 patients, all CD34+ cells expressed CD38 (categories 3 and 4). In the remaining 27 patients, only cells were found which dimly expressed CD34 or did not express CD34 (categories 5 and 6). Of the 93 patients, 88 were treated with intensive chemotherapy according to the protocol of the German AML Cooperative Group. Of these, 21 died early and were not evaluable for treatment response. Complete remission was achieved in 14 of 22 patients (64%) in categories 1 and 2, in 19 of 26 patients (73%) in categories 3 and 4, and in 18 of 19 patients (95%) in categories 5 and 6. The event-free survival was significantly longer in patients of categories 5 and 6 compared to patients in categories 1 and 2 (p less than 0.01) and categories 3 and 4 (p less than 0.05), respectively. We conclude that in the majority of AML patients the immunophenotype of leukemic cells follows the early cell differentiation pathways defined by coordinated expression of CD34 and CD38 similar to that of normal hematopoietic progenitors. The presence of cells in the late cell differentiation stages (CD34+/-, CD38 /+) identifies patients with a higher complete remission rate and longer complete remission duration.

ADP-ribosyl Cyclase↗
PubMed1992

Combined effect of very early intensification and prolonged post-remission chemotherapy in patients with AML.

The study combines the effects of prolonged postremission chemotherapy with that of very early intensification. 900 adult patients at all ages with newly diagnosed AML uniformly received TAD for induction and consolidation followed by monthly myelosuppressive maintenance for 3 years. In patients of 60+ years with persistent bone marrow blasts a second TAD course was given. In all patients of less than 60 years a second induction course started on day 21 even in aplasia with no blasts. Second induction was randomly either TAD or HAM. In the younger age group 69% attained CR and similar in the two arms the CR rate after 5 years is 35%. Including the 50% patients attaining CR in the higher age group the CR rate after 5 years is 32%. In 40 patients receiving allogeneic BMT and 21 patients receiving autologous BMT in first CR relapse free survival is similar to that from chemotherapy alone in a matched pair analysis. We conclude that age adapted very early intensification followed by prolonged postremission chemotherapy represents a therapeutic progress.

Adolescent↗
PubMed1992

Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG.

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.

Acute Disease↗
PubMed1992

Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system.

In an attempt to identify prognostic factors for survival and leukemic transformation, 235 untreated patients with primary myelodysplastic syndromes (MDS) were analyzed in a single center retrospective study. To the well known FAB classification of MDS a supplementary group of patients with pure sideroblastic anemia (PSA) was added, characterized by the absence of dysplastic features of non-erythroid cells. Accordingly, the morphological subtypes were refractory anemia (RA), n = 55; PSA, n = 40; RA with ring sideroblasts (RARS), n = 33; RA with excess of blasts (RAEB), n = 53; RAEB in transformation (RAEB/T) n = 29; and chronic myelomonocytic leukemia (CMML), n = 25. Having screened 28 clinical, cytological, and laboratory parameters by univariate analysis, multiple regression analysis identified six variables with independent prognostic value: percentage of bone marrow blasts, serum LDH activity, PSA, hemoglobin concentration, age, and platelet count. If patients with PSA were excluded, the FAB classification no longer contributed independent prognostic information. Based on the results of this multivariate analysis, a simple scoring system was devised for predicting the survival of patients with MDS. A score of unity was allocated to each of the following parameters: bone marrow blasts greater than or equal to 5%, LDH greater than 200 U/I, hemoglobin less than or equal to 9 g/dl, and platelets less than or equal to 100 x 10(9)/I. As a function of their total score, patients were divided into three risk groups (group A, score 0; group B, score 1-2; group C, score 3-4), which differed significantly in both survival and rates of leukemic transformation. The cumulative survival 2 years after diagnosis was 91% in group A, 52% in group B, and 9% in group C (p less than 0.00005). The actuarial risk of transformation to acute myeloid leukemia at 2 years was 0, 19, and 54%, respectively (p less than 0.05). The inclusion of LDH enzyme levels qualified this scoring system for an accurate assessment of patients with CMML whose prognosis is viewed too favorably when rated by other scores. Furthermore, this score was able to identify those patients with RA and RARS who, without showing an excess of marrow blasts, have an unfavorable prognosis.

Adolescent↗
PubMed1991

[Therapy of multiple myeloma by allogeneic bone marrow transplantation].

Multiple myeloma of IgG kappa type was diagnosed in a 42-year-old man with bone pains, dyspnoea on exertion and increasing drowsiness. Six chemotherapy cycles extending over 14 weeks and consisting of 15 mg/m2 melphalan intravenously on day 1 and 60 mg/m2 prednisolone orally on days 1-4 produced a partial remission. As the HLA-identical sister of the patient was willing to donate bone marrow, an allogeneic marrow transplantation was planned. After 7 days' conditioning treatment (hyperfractionated whole-body irradiation with 12 Gy, chemotherapy with 70 mg/m2 melphalan and 60 mg/kg cyclophosphamide), 4.2 x 10(8) nucleated cells of donor marrow were infused per kg recipient body-weight through a central venous catheter. Despite prophylaxis with short-course methotrexate and cyclosporin, an acute graft-versus-host reaction of grade II-III occurred on day 26, though it settled almost completely after treatment with daily 2 mg/kg prednisone and monoclonal interleukin-2 receptor antibodies (B-B10, daily 10 mg). On day 100 after the marrow transplantation, marrow puncture showed the picture of complete remission with normal regeneration of haemopoietic cells. Allogeneic marrow transplantation may therefore be considered as a new and promising mode of treatment for younger patients with multiple myelomas.

Acute Disease↗
PubMed1991

Granulocyte colony-stimulating factor (G-CSF) treatment in a neutropenic leukemia patient with diffuse interstitial pulmonary infiltrates.

Adult respiratory distress syndrome (ARDS) in patients suffering from acute leukemia usually occurs during chemotherapy-induced neutropenia. In addition, intensified chemotherapy with high-dose cytosine arabinoside and mediastinal irradiation may contribute to the development of ARDS. This complication is usually refractory to conservative treatment with antibiotics, steroids, and mechanical ventilation. In this report, we describe a 25-year-old patient with acute lymphoblastic leukemia who developed ARDS during the phase of chemotherapy-induced neutropenia. Subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) at doses of 300-600 micrograms/day led to a prompt increase of peripheral granulocyte counts. With resolution of neutropenia, respiratory function gradually improved, and mechanical ventilatory support was stopped after 2 weeks. From this observation we surmise that the application of G-CSF may be an effective therapeutic approach for preventing the fatal outcome of ARDS in leukemia patients with bone marrow aplasia.

Adult↗
PubMed1991

Serum erythropoietin concentrations in patients with myelodysplastic syndromes.

Medullary dyserythropoiesis with reduced production of erythrocytes is an early and consistent feature of myelodysplastic syndromes (MDS). The mechanism underlying the disturbed red cell proliferation and maturation is presently unknown. In order to study the role of erythropoietic growth factors, we determined by radioimmunoassay the serum concentrations of immunoreactive erythropoietin (Epo) in 42 non-transfused patients with primary and secondary MDS. Their median hemoglobin concentration at the time of Epo measurement was 9.1 g/dl (range, 5.7-14.6). Compared with the control group, 83% of the MDS patients had increased serum Epo levels, ranging from 26-4530 mU/ml. Although in the entire patient population an inverse relationship between serum Epo and hemoglobin concentrations was noted (r = -0.35; p = 0.02), Epo titers differed markedly between patients at comparable degrees of anemia. In 7 patients presenting with a hemoglobin concentration between 5.9 and 11.9 g/dl, excessive elevations of Epo levels (greater than 500 mU/ml) were found. In contrast to previous observations, serum Epo concentrations were not shown to correlate with the percentage of erythroblasts in the bone marrow. There was, however, a significant relationship between the Epo activity and the degree of medullary dyserythropoiesis, as assessed by morphological criteria (p less than 0.01). From these data we conclude that the anemia in MDS is not due to an endogenous Epo deficiency. The marked variability of Epo production in these disorders is not fully explained by the degree of anemia, but may also reflect inherent abnormalities of the myelodysplastic erythropoiesis.

Adolescent↗
PubMed1991

Treatment of advanced myelodysplastic syndromes with recombinant interferon-alpha 2b.

We examined the efficacy and toxicity of recombinant interferon-alpha 2b (rIFN-alpha 2b) in 10 previously untreated patients with advanced myelodysplastic syndromes. Morphological subtypes were refractory anaemia with excess of blasts (RAEB) in 4, RAEB in transformation (RAEB/T) in 3 and chronic myelomonocytic leukaemia (CMML) in 3 cases. IFN was administered subcutaneously at increasing doses of 1 to 3 x 10(6) IU per day. The median duration of therapy was 6 months (range, 3 to 14). 2 patients, both with a diagnosis of CMML, achieved a complete and partial remission, respectively. In the complete responder, remission could be maintained for 9.5 months by daily administration of 1 x 10(6) IU IFN. The other patients were classified as failures, although in 4 cases a decrease of bone marrow blasts was noted and none of the patients progressed to overt leukaemia while being treated with IFN. During the study, all patients with RAEB and RAEB/T showed a moderate to severe reduction in peripheral leukocyte and platelet counts, requiring premature termination of IFN therapy in 5 cases. Despite adequate supportive measures, 2 patients died of pneumococcal pneumonia and gastrointestinal bleeding, respectively. In 1 patient, IFN therapy had to be stopped because of neurologic toxicity (polyneuropathy). From these data we conclude that rIFN-alpha 2b at the doses and schedule tried is not a useful treatment for advanced myelodysplastic syndromes. Patients with CMML, however, may be an exception and should further be considered as candidates for therapeutic trials with rIFN-alpha 2b.

Acetaminophen↗
PubMed1991

[The influence of the duration of infusion on the acute toxicity of amphotericin B. Comparison of two hour versus four hour infusions].

A prospective, randomized, double-blind crossover study was performed to compare the incidence and severity of amphotericin-B-induced acute toxicity (chills, fever, nausea and vomiting) after two- and four-hour infusions in 33 leukemic patients with suspected or microbiologically proven systemic fungal infections. Each patient was treated in an alternating fashion of two- and four-hour infusions every other day. Toxicity was graded according to modified WHO-criteria. Evaluation of 264 infusions revealed no difference between the two schedules neither in incidence nor severity of acute toxic reactions. These data indicate that amphotericin B given over 2 hours is equally well--or poorly (!)--tolerated than the four-hour regimen.

Adult↗