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Overwhelming Post-Splenectomy Infection (OPSI or PSS), most frequently caused by encapsulated Gram-positive pathogens, is a complication after splenectomy. Reasons for splenectomy include trauma, or malignant and non-malignant hematologic diseases. OPSI-inducing bacteria are mainly Streptococcus pneumoniae and less frequently Haemophilus influenzae, Neisseria meningitides and Gram-negative bacilli. There exist very efficient--albeit often neglected--strategies, how to prevent infections in patients after splenectomy. These include vaccination, prophylactic antibiotics (always for 3 years during childhood and adolescence) and prompt antibiotic treatment, if an infection is suspected. Patients need to know the nature and likelihood of PSS and they should seek immediate medical attention if they become ill or febrile. Each patient should carry at all times a letter or card documenting the splenectomy. With these measures and precautions, the PSS-risk can be significantly reduced or at best be completely avoided.

The chance diagnostic finding of thrombocytopenia occasionally happens during the course of basic laboratory diagnostics (hemogram). This article explains possible differential diagnoses.

In one centre (the medical department of the University of Ulm), over a period of 25 years, the diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) had been made in 40 patients (27 women, 13 men). The data on these patients were analysed and the findings compared with those reported in the literature. Criteria for inclusion were a positive sucrose haemolysis and acid-serum test. Leading clinical symptoms were anaemia, tendency towards bleeding and infections, haemolysis, abdominal pain and thromboembolism. The age at which main symptoms first appeared was most often in the third and fourth decade of life. The sex ratio of 2:1 (female to male) was unusual. PNH was frequently (in 22 patients) associated with aplastic anaemia. If bone marrow transplantation, at present the only curative procedure, was not possible and there was PNH alone, treatment was supportive and directed at relief of symptoms. The course of the disease was highly variable. Lack fo prognostic criteria made it difficult to define indications for intensive therapeutic measures. While haemolytic crisis and thromboembolism are frequent complications in isolated PNH haematopoetic insufficiency defines clinical outcome in PNH combined with aplastic anaemia.

Eight patients with relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with alpha-interferon and leukocyte transfusions of the bone marrow donor. Six patients responded with disappearance of leukemic cells (Ph1, BCR-ABL) and reestablished donor hemopoiesis. All six patients developed bone marrow hypoplasia and graft-versus-host disease (GvHD). Three of the six patients died of cerebral bleeding, infection and GvHD, respectively. The remaining three patients are alive and well at day 418, 677, 818 after leukocyte transfusions. Two patients relapsed with more advanced disease of CML after BMT and failed treatment. Donor leukocyte transfusions provide an effective therapy for patients with relapsed CML after BMT, but are associated with a high mortality due to bone marrow hypoplasia and GvHD.

A 75-year-old man with angiodysplasia of the sigmoid and rectum and recurrent lower gastrointestinal bleeding episodes, despite repeated endoscopic laser-coagulation, was successfully treated with oestrogen-progesterone. Besides angiodysplasia he had aortic valvular stenosis, monoclonal gammopathy, mild renal insufficiency, and moderate peripheral arteriosclerosis obliterans. Oestrogen-progesterone may be a valuable alternative therapy in elderly patients with repeated bleeding, despite endoscopic coagulation, secondary to gastrointestinal angiodysplasia which cannot be treated surgically, in patients who deny surgery, or with rebleeding after surgery.

In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.

Uncertain gait and weakness on standing, progressing to flaccid paraparesis of both legs, developed in a 76-year-old woman. Proprioceptor reflexes of both legs were absent and there was pallaesthesia up to the pelvic rim. Electromyography pointed to polyneuritis. Administration of prednisone, 1 mg/kg daily for 10 days, was ineffective, as was one-time plasmapheresis. An incomplete tetraparesis developed. Blood white-cell count increased within 2 weeks by 10,400/microliters (52% lymphocytes) to 17,400/microliters. Blood smear, bone-marrow cytology and histology, as well as immunocytology, revealed lymphoplasmocytoid immunocytomas (chronic lymphocytic leukemia). Oral cytoreductive treatment was started with chlorambucil, 0.1 mg/kg daily, and prednisone, 100 mg daily. After 19 days the patient was able to walk with support, after 28 was walking unaided. Treatment was continued over eight cycles (14 days' treatment, 14 days' interval per cycle). 17 weeks after onset of treatment paraesthesias of the legs required renewed administration of chlorambucil, 0.1 mg/kg per day, for 3 months. The patient has now been free of symptoms during a follow-up period of 12 months.

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, 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 September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.

The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.

Interdisciplinary cancer conferences (ICC), which deal with the problems of individual patients, are an appropriate instrument for coordinating interdisciplinary decisions at an early stage and for ensuring adherence to standard diagnostic and therapeutic procedures. As shown by seven-years experience and data from 1225 cases, about 80% of the decisions made by the conference are followed by the responsible physician. Regular meetings at suitable times and locations, effective preparation with information about the problems to be discussed and rapid distribution of written reports to all participants will guarantee a continuing interest in presenting patients at the ICC.

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.

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.

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.

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.