Lack of efficacy of high-dose intravenous immunoglobulin in autoimmune haemolytic anaemia: a clue to its mechanism.

5 patients with autoimmune haemolytic anaemia (AIHA) of warm type (4 idiopathic, 1 associated with systemic lupus erythematosus and thrombocytopenia) were treated with high doses of i.v. immunoglobulin (IgG; Sandoglobulin; 2.0 g/kg body weight). IgG therapy was ineffective in all 5 cases as indicated by a lack of clinical improvement, continuous signs of accelerated red blood cell (RBC) destruction, and an unchanged survival rate of 51Cr-labelled autologous RBC in 4 patients studied. IgG infused at equivalent doses into 5 healthy volunteers led to an increase of IgG coating of autologous RBC (irrespective of the ABO blood groups) without concomitant changes of haemoglobin, haematocrit or reticulocytes, increase of serum IgM in 3/5, a decrease of serum C4 in 5/5, and a decrease of serum haptoglobin in 2/5 individuals. We conclude that IgG at a dose of 2.0 g/kg body weight is ineffective in AIHA. This may be caused by an increased, though clinically inapparent, interaction of IgG-coated autologous RBC with the mononuclear phagocyte system.

Staging systems for multiple myeloma: a comparison.

In 152 patients with multiple myeloma who had been treated with cytostatic agents the prognostic value of seven staging systems was evaluated: Carbone et al (1967); Acute Leukemia Group B (ALGB) and Eastern Cooperative Oncology Group (ECOG) (Costa et al, 1973); Southeastern Cancer Study Group (SECSG) (1975); Durie & Salmon (1975); Alexanian et al (1975); Merlini et al (1980); British Medical Research Council (1980). The staging systems of the ALGB (Costa et al, 1973) and SECSG (1975), both dividing patients into 'good risk' and 'poor risk' groups, showed significantly different survival curves. Nevertheless, despite statistical significance the observed differences were rather small. In the systems of Carbone et al (1967), Merlini et al (1980), Alexanian et al (1975) and Durie & Salmon (1975) some of the differences in the survival curves were statistically significant while others were not. Our data best fitted into the British Medical Research Council (1980) staging system, the survival curves of all three stages showing significant differences, with median survival time dropping from 83 months in stage A to 52 months in stage B and 26 months in stage C. Nevertheless, none of those systems was clearly superior to single risk factors, especially creatinine and haemoglobin.

IgG therapy in autoimmune haemolytic anaemia of warm type.

Three patients with autoimmune haemolytic anaemia of warm type were treated with high doses of intravenous immunoglobulin (Sandoglobulin). The therapy was ineffective in all three cases. The possible reasons for this therapeutic failure are discussed.

cis-Platinum (DDP) and VP 16-213 (etoposide) combination chemotherapy for advanced non-small cell lung cancer. A phase II clinical trial.

Forty-six patients with non-small cell lung cancer were treated with a combination of cis-platinum, 90 mg/m2 i.v. on day 1 and VP 16-213, 100 mg/m2 i.v. on days 1, 3 and 5. The overall remission rate was 22%, with a median duration of 7 months. Squamous cell and large cell undifferentiated carcinomas responded in 27 and 22% of patients, and seven patients with adenocarcinoma did not respond to chemotherapy. Survival was 7 months for all patients, 11.5 months for responders (7-27+), 8.5 months for patients with stable disease (3-27+) and 5 months for progressive tumours (1-9). Prognosis was adversely influenced by a performance status of less than 80%, a weight loss of more than 10 kg during the last 3 months before start of treatment and a radiologically demonstrable 'major' atelectasis (collapse of at least one superior or inferior lobe of the lung). Only one out of 31 patients with one or more poor prognostic factors came into remission. In contrast, nine out of 15 patients without poor prognostic factors showed objective tumour regression (60% remission rate). Stage and age did not affect the results. Haemotologic and renal toxicity were mild, but poor subjective tolerance (nausea, vomiting, loss of appetite) was prominent.

[Results of drug therapy of inoperable non-small cell lung carcinoma with VP 16-213 (Etoposide) and cis-platin. A phase II study]. / Ergebnisse der Chemotherapie inoperabler nicht-kleinzelliger Bronchialkarzinome mit VP 16-213 (Etoposid) und Cis-Platin. Eine Phase-II-Studie.

Forty-six patients with non-small cell lung cancer were treated with a combination of cis-platinum 90 mg/m2 i.v., day 1 and VP 16-213 100 mg/m2 i.v. on days 1, 3 and 5. The overall remission rate was 22% (10 out of 46 patients) with a median remission duration of 7 months. Squamous cell and large cell undifferentiated carcinomas responded to the chemotherapy with a remission rate of 27% (7 out of 26 patients) and 22% (3 out of 13 patients). Seven patients with adeno-carcinoma did not respond to chemotherapy. The overall survival was 7 months (1-27+). The survival time for patients entering remission was 11.5 months (7-27+), for those with stable disease 8.5 months (3-27+), and for patients with progressive disease 5 months (1-9). Performance status of less than 80%, a weight loss of more than 10.0 kg in the last three months before starting treatment and a "major" atelectasis (collapse of at least one superior or inferior lobe) adversely influenced prognosis. Only 1 out of 31 patients with one or more poor prognostic factors came into remission. In contrast, 9 out of 15 patients (60%) without poor prognostic factors had a remission. Stage, limited versus extensive disease, and age did not affect the results. Hematologic and renal toxicity of the combination were mild, but poor subjective tolerance (nausea, vomiting, loss of appetite) was prominent.

[Indications and clinical aspects of granulocyte transfusions (author's transl)]. / Indikation und Klinik der Granulozytentransfusion.

Granulocyte transfusions (n = 222) were administered to 41 patients with granulocytopenia (less than 500 X 10(6)/1) and antibiotics-resistant infections. The average granulocyte content per transfusion was 2.1 X 10(10), 212 transfusions had been obtained by filter leucapheresis. Infections improved in 25 episodes, and 18 patients survived the 30th day. There was no influence in 18 episodes and only 2 patients survived beyond the 30th day. Extent and duration of bone marrow insufficiency, and type and grade of infection, clearly influenced prognosis. Further prognostically relevant risk factors were age (greater than 60 years) and platelet deficiency (less than 20 X 10(9)/1), as well as liver and renal insufficiency. Adherence to precise guidelines may prevent pointless transfusions.

Clinical and prognostic heterogeneity of non-Hodgkin lymphomas of high-grade malignancy.

Comparison of clinical data of 64 patients with centroblastic lymphoma, 55 patients with immunoblastic lymphoma and 31 patients with lymphoblastic lymphoma not only confirmed the original assumption of high-grade malignancy as proposed by the concept of the Kiel classification but also demonstrated distinct clinical differences, particularly between lymphoblastic lymphoma and the two other entities. Rapid lymph node enlargement as well as steep fall of survival curves within the first year after diagnosis were common characteristics. Bimodal age distribution, predominance of males and early generalization of disease were typical features of lymphoblastic lymphoma; elderly patients and patients with the unclassified subtypes of lymphoblastic lymphoma exhibited the worst prognosis. Whereas patients with centroblastic and immunoblastic lymphomas showed similar distribution of age, sex and initial stage of disease, patients with immunoblastic lymphoma presented more frequently with a reduced performance status and showed a poorer response to radio- and chemotherapy resulting in a worse prognosis discernible after the first year of follow-up. Generalization during course of the disease was significantly more frequent in immunoblastic than in centroblastic lymphoma.

[Discontinuous cell separation as depletion therapy in chronic leukemias]. / Die diskontinuierliche Zellseparation als depletorische Therapie bei chronischen Leukämien.

Blood cell separators have been successfully used in the treatment of chronic leukaemias. With the intermittent flow system Haemonetics model 30, we found it important to collect 150-300 ml buffy coat/cycle in order to obtain a substantial depletory effect. In 2 patients with chronic myeloid leukaemia on short-term leukapheresis and in 1 patient with prolymphocytic leukaemia on long-term leukapheresis we found a definite decrease in the WBC count. 2 of them experienced a transitory improvement of their disease. Only minor side-effects occurred. However, the loss of erythrocytes and plasma albumin necessitated replacement therapy. From our experience the intermittent flow blood cell separator can be successfully used in the treatment of well-defined forms of chronic leukaemia.

[Results of treatment with ABVD in C-MOPP-resistant Hodgkin's disease (author's transl)]. / Behandlungsergebnisse mit dem ABVD-Schema bei C-MOPP-resistentem Morbus Hodgkin.

22 Patients were treated with ABVD, 19 (18 stage IV B 1 stage III B) could be evaluated. No patient with impaired but 7 of 13 patients with intact bone-marrow function achieved a complete remission. A complete remission was also achieved by all 4 patients with a treatment- and disease-free interval but only by 3 of 15 without a free interval. Pretreatment, histology, duration of disease, and age showed no clear prognostic significance with respect to induction of remission. Toxicity was severe especially in patients over 50 years of age. 2 patients discontinued therapy because of gastro-intestinal toxicity. 2 of 8 died of treatment-related causes (1 leukemia, 1 sudden cardiac death). In 3 patients with high-dose mediastinal irradiation a pneumonitis secondary to bleomycin contributed significantly to death. Our results suggest that ABVD is an effective salvage-regimen for some subgroups of MOPP-failures.

[Allergic alveolitis following inhalation of mould spores from pot plant earth (author's transl)]. / Allergische Alveolitis durch Inhalation von Schimmelpilzsporen aus Blumenerde.

Acute exogenous allergic alveolitis with the typical symptoms of unproductive cough, dyspnoea on exertion, fever, loss of weight, headache and limb pains was observed in a 24-year-old bank employee. Leucocytosis was accompanied by raised ESR; pronounced hypoxaemia and marked restrictive ventilatory defects were found. X-ray changes consisted of severely increased fine reticular interstitial shadowing. The differential diagnosis of allergic alveolitis was confirmed by the demonstration of precipitating antibodies in serum against Pullularia pullulans, Trichoderma viride, Cephalosporium acremonium and Aspergillus fumigatus, moulds with an ubiquitous occurrence. Typical changes of alveolitis were found histopathologically and immunohistologically in the lung tissue after a mini-thoracotomy. The source of exposition leading to the disease were pot plant earth and containers in the patient's flat. Moulds could be isolated from these substrates.

The clinical significance of platelet-associated IgG: a study on 298 patients with various disorders.

Platelet-associated IgG (PAIgG) was studied by a quantitative platelet radioactive anti-IgG test (PRAT) in 298 patients. At the time of investigation, 171 patients were thrombocytopenic (platelet count < 100 X 10(9)/l), 127 had normal platelet counts. Patients fell into the following disease categories: Idiopathic thrombocytopenic purpura (ITP) (N = 81), possible ITP (19), acute ITP (9), systemic lupus erythematosus (22), autoimmune haemolytic anaemia of warm-type (18), systemic blood disease (65), liver diseases (35), other (49). A significant elevation of PAIgG was found in all disease categories. There was a significant correlation between PAIgG and the reciprocal values of platelet counts for most disease groups. No relationship was discernible between PAIgG and hypergammaglobulinaemic states (serum IgG > 1.8 g/l). Platelet survival studies (N = 30) revealed that normal and increased values of PAIgG were associated with normal or shortened platelet mean life span. It is concluded that an elevated PAIgG is only one of several factors involved in the development of immunologically medicated thrombocytopenia.

[Therapy results in hairy cell leukemia]. / Therapieergebnisse bei Hairy-cell-Leukämie.

20 patients with hairy cell leukemia were treated between 1966 and 1978. All modalities of treatment for lymphoproliferative disorders have been used in at least some patients. Besides prednisone, vincristine, cyclophosphamide and their combinations as well as irradiation of enlarged spleens, cell depletion was achieved by splenectomy and leukapheresis. Cytostatics had no beneficial effect. Cytostatic therapy exposed some patients to the hazards of severe infections. On the contrary splenectomy lead to the improvement of some blood parameters. Leukapheresis seemed to work nearly identically. The survival of the splenectomized patients was longer than of controls. Because of the variability of the duration of the disease no definite statement could be made concerning the survival of both groups. 12 patients died during the observation period. Splenectomy was followed by one death, 11 patients died of septicemia.

Intensive leukapheresis as initial therapy for chronic granulocytic leukemia.

Intensive leukapheresis has been used as the initial treatment of chronic granulocytic leukemia (CGL) in six patients. The number of leukaphereses ranged from 3 in 7 days to 13 in 39 days (mean, 8 in 22 days). The procedures were well tolerated, and in all patients there was improvement in hematologic values, in most cases with considerable reduction in the peripheral leukocytosis and thrombocytosis and in the proportion of immature granulocytic cells in the circulation. Splenomegaly decreased considerably in the four patients who had more than four leukaphereses. Symptoms of sweating, malaise, and pain due to splenomegaly were rapidly relieved. Problems due to hyperuricemia did not occur, but four patients required blood transfusions for correction of anemia. This method of initial treatment of CGL appears to give more rapid relief of symptoms than does conventional chemotherapy; it incurs no risk of hyperuricemia and lessens that associated with thrombocytosis. In addition, large quantities of granulocyte-rich plasma are made available for the treatment of infections in neutropenic patients. Intensive leukapheresis deserves more widespread evaluation as the initial treatment of CGL.