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Bei 50 Patienten mit primarer Panmyelopathie wurde der Erythrocytenumsatz mit Hilfe der Cr51-Markierung untersucht. In den meisten Fallen ergab sich eine masige Verkurzung der Erythrocytenlebenszeit, wahrend sich nur in der Minderzahl der Falle eine absolute Senkung der Produktionsrate eindeutig nachweisen lies. Die Anamie ist also im allgemeinen durch einen beschleunigten Erythrocytenabbau bei relativer Insuffizienz des erythropoetischen Knochenmarks bedingt. Aus den Reticulocytenzahlen konnen bei Panmyelopathien keine sicheren Ruckschlusse auf den peripheren Erythrocytenumsatz gezogen werden.

ZusammenfassungBei gesunden Versuchspersonen wurde eine Radiochrommarkierung der Erythrozyten in vitro und in vivo durchgeführt und der Aktivitätsverlauf im Blut, sowie über Herz, Milz und Leber beobachtet. Die dabei gewonnenen Normalwerte und die prinzipiellen Unterschiede der beiden Methoden werden vor allem in Hinblick auf ihre Anwendung in der klinischen Diagnostik besprochen.

ZusammenfassungDie Aufnahme und Bindung von DFP32 durch rote Blutzellen wurde in vitro untersucht. Dazu wurden Kaninchenerythrozyten unter verschiedenen Bedingungen mit der genannten Substanz inkubiert. Die Aufnahme in Abhängigkeit von der zugesetzten DFP32-Konzentration zeigt einen zweiphasischen Verlauf, der als Ausdruck verschiedenartiger Bindungsprozesse zu deuten ist. Die spezifische Bindungskapazität der Kaninchenerythrozyten liegt etwa bei 0,2 μg DFP32/ml. Die darüber hinaus aufgenommene Substanz läßt sich in vitro und in vivo in 6 Stunden weitgehend wieder aus den Zellen eliminieren, so daß man annehmen kann, daß auch die nach In-vivo-Markierung beobachtete Frühelution des DFP32 auf einer „unspezifischen” Bindung des Stoffes an die Erythrozyten beruht. Retikulozyten können etwas mehr DFP32 aufnehmen als reife rote Blutkörperchen. Die Bedeutung dieser Befunde für die Erythrozytenmarkierung mit DFP32 als Methode der Erythrozytenlebenszeitbestimmung wird diskutiert.

Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow target with cyclosporin A (CyA; 0.5 microgram/ml) or with a monoclonal anti-gamma-(immune) interferon (IFN-gamma) antibody. Both effects were highly correlated. The data indicate that (a) endogenous elaboration of IFN-gamma may contribute to decreased colony formation in allogeneic bone marrow transplant recipients, and (b) CyA may induce a gradual release of the progenitor cell pool from IFN-gamma-mediated suppression.

In a first small study the chlorinated hydrocarbons present in the bone marrow of haematologically normal persons and of 6 randomly selected patients with severe aplastic anaemia have been identified and quantified by glass-capillary gas chromatography. We found great interindividual differences in the concentrations of these compounds both within the control group and within the patient group, but no definite difference between the two groups. So far, we have been unable to detect known toxic concentrations of chlorinated hydrocarbons in any of our samples, which could have supported the idea of a deficiency in the metabolism of these chemicals in some patients with aplastic anaemia.

The aim of the study was to improve remission quality through application of an intensified induction therapy successful in childhood ALL; in a modified form for patients of 15-35 years and in a reduced form for patients of greater than 35-65 years with ALL or AUL. The 8-week induction therapy consists of two phases. In phase I, prednisone, vincristine, daunorubicin, and L-asparaginase are given and in phase II, cyclophosphamide, cytosine-arabinoside, and 6-mercaptopurinee. As CNS-prophylaxis, intrathecal methotrexate, and CNS-irradiation with 24 Gy are used. After 3 months a re-induction therapy similar to the induction therapy is given with dexamethasone and adriamycin instead of prednisone and daunorubicin and without L-asparaginase. Maintenance therapy with 6-mercaptopurin and methotrexate follows over a period of 2 years. Since the formation of the study group in 1979 up to 30.06.81, 170 patients from 25 hospitals with newly diagnosed ALL or AUL were treated according to the protocol. Up to 30.11.81, 162 patients had completed treatment and were evaluable. Of these, 77.8% achieved complete remission, 80.7% in the age group 15-35 years and 68.3% in the age group greater than 35-65 years. The median survival time for all patients was 24 months and for the 126 patients with complete remission the median has not yet been reached (last observation 31 months). The median remission duration is 20 months. Prognostic factors for remission duration are (1) the number of chemotherapy courses required to reach complete remission, (2) the immunological subtype, (3) age and (4) initial leukocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

The current status of the prospective German multicenter study on the therapy of chronic myelogenous leukemia (CML) is reported. After three years 188 of the projected 300 patients have been randomized. The duration of the study will be 8 years. The clinical characteristics of the randomized patients correspond well to those reported in the literature. Risk factors are distributed equally in both arms. One problem is the relatively high drop-out rate of about 12% thus far. Survival curves for the two treatment arms will be presented, although at present the number of patients having reached the end of the chronic phase is too small to allow definitive evaluation.

The case of an immunoblastic lymphadenopathy with a leukaemoid reaction has been observed. All the clinical, serological and histological features described by previous authors were present. In addition, there were more than 1000000/mul nucleated peripheral cells, consisting of mature and a few immature granulocytes, a small number of normoblasts and many lymphocytes, "immunoblast-like" lymphoid cells and plasma cells. Polyclonality of the latter was demonstrated by serological methods. Spontaneous remission occurred and was apparently enhanced by the application of corticosteroids.

For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.

Two patients treated for acute leukaemia with BCNU, cyclophosphamide and cytosin-arabinoside are reported, in whom pulmonary fibrosis developed and progressed during therapy. The development of lung fibrosis during combined treatment, together with serological exclusion of other diseases known to be associated with pulmonary fibrosis, make a causal connection between the treatment and the fibrosis very probable.

A new immunoglobulin preparation (Sandoglobulin) was administered to 20 patients, a total of 49 infusions at a dose averaging 12.6 gamma-globulin per infusion. Twelve patients had congenital or acquired immunoglobulin deficiency, in come of them very severe. A In-vivo recovery, on the basis of an estimated plasma volume, averaged 85% of expected values. Half-life on repeat substitutions was over 20 days. There were no severe side-effects or changes in important biochemical values. In one woman with an antibody deficiency syndrome fever regularly developed after several infusions, but it always fell to normal spontaneously after several hours. In two women followed for some time, both with severe antibody-deficiency syndrome, there was a definite decrease in severity and frequency of pulmonary infections.

Of 75 patients with asplastic anaemia treated between 1968 and 1975, 33 were retrospectively considered as potential candidates for allogenegic bone-marrow transplantation on the basis of their age and severity of marrow failure. The prognosis of these patients with conservative treatment was assessed from parameters obtained at the time of the initial diagnosis. Initial peripheral-blood granulocyte or platelet concentrations were not of porgnostic value. In contrast, initial reticulocyte concentrations, allowed separation of the patients into two groups with poor and good prognosis. Low initial reticulocyte concentrations (less than 10 000/mu1) indicated those patients at extremely high risk of succumbing to their marrow aplasia (there were no survivors 36 months after disgnosis). In contrast, 75% of those patients with more than 10 000 reticulocytes per mu1 at diagnosis survived for 3 years. Initial peripheral-blood reticulocyte concentrations thus appear to indicate the extent of the marrow failure in aplastic anaemia more accurately than granulocytes or platelets. Low initial reticulocyte concentrations may indicate, among patients with severe aplastic anaemia, those for whom allogeneic bone-marrow transplantation should be seriously considered; patients with higher initial reticulocyte concentrations may benefit from conservation treatment.

The pathomechanisms which cause the obliteration of the hemopoietic system in aplastic anemia are poorly understood, the fate of an individual patient unpredictable and the overall prognosis bad.

Drug-induced agranulocytosis comprises a severe selective neutropenia in a hypersensitive individual. The compelling problem in a single case to determine the etiology of agranulocytosis results from multiple drug consumption, use of composed preparations and the unknown relative risk of most of the incriminated drugs. Immune and toxic mechanisms may be involved, however, the underlying pathomechanism does not correlate with typical hematological and clinical features of agranulocytosis. Prognosis is associated with the infectious state of the patient and the duration of the neutropenic phase which reflects the degree of impairment of bone marrow hemopoiesis. After withdrawal of all potentially hazardous drugs treatment of agranulocytosis follows the therapeutical approach in severe neutropenias due to cytostatic drug exposure.

In a retrospective study, total antimicrobial decontamination with strict reverse isolation (ITD) and selective decontamination without isolation (SD) were compared as means of preventing infection in patients with acute leukaemia. Thirty patients were treated with ITD and 34 patients with SD. The surveillance cultures indicated that aerobic gram-negative bacilli and yeast could be equally eliminated effectively in both the groups. The anaerobic flora was only minimally influenced by SD. The incidence of acquired infections was 1.17 per patient in group ITD as compared to 0.85 in group SD. In group ITD, acquired bacterial infections were mostly caused by gram-negative bacilli (63%) whereas in the group SD these microorganisms accounted only for 25% of the infections. In group SD the total number of fever days was significantly lower and the mean duration of pyrexial episodes was substantially shorter. The results indicate that SD is an effective and inexpensive method for preventing gram-negative infections and might be at least as effective as ITD.

From 1967 to 1972, 70 patients with aplastic anemia were observed and followed up to death or at least two years. 3 cases of pure red cell anemia, and 2 cases of amegakaryocytic thrombocytopenia are included. Detailed investigation of drugs taken within 6 months before onset of the disease revealed chloramphenicol in 20, butazones in 11 cases. Acute viral hepatitis preceded the hemopoietic failure in 2 patients. In addition to various combinations of anemia, granulocytopenia and thrombocytopenia, monocytes were diminished in 35 and lymphocytes in 12 cases. Acid serum or sucrose tests were consistently negative. The patients were treated by short-term prednisone, long-term androgens and red cell and platelet substitution as needed. 2 years after onset of the disease, 33 per cent were in partial or complete remission, 30 per cent survived without remission, and 35 per cent had decreased. Correlation of various parameters with remission and survival showed the presence of a subgroup at risque, comprising patients with low marrow cellularity and clinically relevant diminution of all three cell lines at the time of diagnosis. Absolute lymphopenia and increase of plasma cells in the bone marrow were of poor prognostic significance. In this subgroup two years after the onset of the disease only 32 percent survivors and 16 per cent remissions were recorded. There was no conclusive evidence for the therapeutic value of prednisone or androgens in our series. The present situation in severe aplastic anemia requires more effective forms of treatment and justifies experimental therapies like bone marrow transplantation.

Nine patients with anorexia nervosa were studied, who had varying degrees of bone marrow failure ranging from a slight neutropenia to severe pancytopenia. In addition to routine laboratory work bone marrow biopsies were performed at admission and during the course of disease. In four of those patients erythropoietin excretion per 24 hours was measured by the bioassay in the polycythemic mouse at least twice during the course of treatment. At admission most bone marrow showed a marked although varying hypocellularity with grossly apparant background gelatinous material, which appeared to consist of acid mucopolysaccharides. Leukopenia and the changes of the bone marrow morphology reversed to normal after refeeding. Erythropoietin excretion was only elevated in patients who were anemic and returned to normal when the haematocrit reached normal levels. It seems therefore unlikely that an impaired production of erythropoietin or other postulated humoral factors cause the haemopoietic changes in anorexia nervosa. A direct effect of fat or carbohydrate depletion and/or of the increased mucopolysaccharides upon the proliferation of the haemopoietic cells can be suggested, but is an entirely speculative preposition.

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25-60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.

The prevalence of antibodies to human T-lymphotropic virus III was determined in acquired immunodeficiency syndrome (AIDS) risk groups by an enzyme linked immunosorbent assay and confirmatory tests in four different areas in West Germany. Twenty-four of 28 homosexual AIDS patients (86%), 24 of 33 homosexual patients with lymphadenopathy syndrome or AIDS related complex (73%), and 44 of 113 asymptomatic homosexuals at risk for AIDS (39%) were seropositive. In three groups of hemophiliacs, 8 of 35 in 1983 (23%), 25 of 65 in early 1984 (39%), and 19 of 23 in late 1984 (83%) showed positive results. Two sera from 36 polytransfused patients were also positive, whereas 36 selected blood donors, and 32 healthy laboratory and clinical personnel were all negative. Also no human T-lymphotropic virus III antibodies were detected in sera of 187 prostitutes in the Munich area.