Interferon-alpha for the treatment of elderly patients with chronic myeloid leukaemia.

The present retrospective analysis is based on data of 213 patients with chronic myeloid leukaemia (CML). They were treated with interferon (IFN)alpha-2C (Berofor) at daily doses of 3.5 MU subcutaneously (s.c.), alone or in combination with low-dose ara-C or hydroxyurea, according to four consecutive studies of the Austrian CML Study Group. Comparisons were made between 41 patients aged > or = 60 years and 172 younger patients. The elderly patients (median: 64 years; range: 60-73) showed similar pretreatment characteristics compared with the younger group, but included a higher percentage of Sokal Stage three (51 vs 20%). Median observation periods were similar (38 vs 39 months), whereas the duration of IFNalpha treatment was shorter in the elderly group (median 57 vs 42 weeks). The rate of overall haematological responses (73 vs 78%) and complete haematological response (44 vs 54%), was similar in both cohorts. Differences seen in partial (5 vs 12%) and complete cytogenetic response (10 vs 13%), were not statistically significant, but a tendency in favour of the younger cohort had to be noted. Summing up, in elderly patients acceptable rates of haematological and cytogentic response can be expected after treatment with IFNalpha alone or in combination with LD ara-C or HU.

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Spontaneous and conA-induced suppressor lymphocytes: a comparative study.

Suppressor monocytes, Concanavalin A(ConA)-induced suppressor T cells, and short-lived suppressor lymphocytes have been describe in humans. The present study was performed to evaluate spontaneous suppression in a test system similar to that employed for the demonstration of ConA-induced suppressor cells: Lymphocytes were either stimulated by ConA (= induced suppressor cells) or immediately mitomycin-treated (= spontaneous suppressor cells). Both preparations were tested for their capacity to suppress mitogen-induced proliferation of autologous cells. Depletion of monocytes or B lymphocytes did not affect spontaneous suppression. The active cells were short-lived in vitro. Therefore the net increase in suppressor activity generated by preculture with ConA is in part related to a loss of spontaneous inhibitory activity in the control cultures kept without mitogen. Spontaneous suppressor cell activity was comparable to that of ConA-induced suppressor cells.

Normal suppressor-cell activity in systemic lupus erythematosus. A study on 26 cases.

Suppressor-cell activity of 26 SLE patients suffering from active disease was compared to that of 15 healthy controls. ConA-induced and spontaneous suppression was evaluated. The mitogen-driven proliferation of normal allogeneic cells was significantly impaired by ConA-induced as well as spontaneous suppressor cells. However, no difference in suppressor-cell activity could be demonstrated between SLE patients and controls.

[Encouraging results with cytostatic therapy in metastasizing breast cancer (author's transl)]. / Erfolge der zytostatischen Therapie beim metastasierenden Mammakarzinom.

58 women with metastatic breast cancer, non-responsive to hormone therapy, were treated with a modified CMF regimen. After progression the combination of adriamycin and vincristine was used. With CMF the response rate was 41% (10% complete remissions, 31% partial remissions), 38% showed no change, whilst progression of the disease was observed in only 21% of patients. The median duration of remission was about 8 months. Progression of the disease was treated by a combination of adriamycin and vincristine and remissions were obtained in 24% of cases. The median survival time of our patients from the time of tumour metastasis was 18.6 months and was dependent on the results of treatment.

[Surface glycoproteins of normal and malignant leukocytes]. / Oberflächenglykoproteine an normalen und malignen Leukozyten.

This study aimed to evaluate the molecular weight distribution patterns and the quantitative expression of surface glycoproteins (S-GP) of various differentiation stages of human leucocytes. S-GP were first exposed by treatment with neuraminidase; subsequently they were labelled by galactose-oxidase treatment followed by reduction with 3H-sodium borohydride. Labelled S-GP were separated on polyacrylamide gels in the presence of SDS and were visualized by means of fluorography. A total of 8 major S-GP bands with apparent molecular weights of 230 000, 215 000, 200 000, 185 000, 175 000, 150 000, 125 000 and 110 000 daltons were identified. All of these S-GP were already expressed at the level of pluripotent myelopoietic stem cells but different in their relative expression during further cellular maturation.

[Results of cytostatic polychemotherapy in non-Hodgkin lymphomas]. / Ergebnisse der zytostatischen Polychemotherapie bei Non-Hodgkin-Lymphomen.

109 patients with advanced stage non-Hodgkin lymphomas were treated with cytostatic chemotherapy. 91 of these patients were classified according to the Kiel classification as having lymphomas of low-grade malignancy, whilst the remaining 18 had lymphomas of high-grade malignancy. The primary treatment in low-grade malignant lymphomas was a combination of chlorambucil and prednisone: in case of progression or therapeutic failure more aggressive schedules (COP, C-MOPP, HOP, CHOP, BACOP) were used. Patients with high-grade malignant lymphomas were treated in the first instance according to these aggressive schedules. Although no complete remissions were achieved, 25 out of the 47 patients with CLL responded with a partial remission to chlorambucil/prednisone, whilst 12 out of 19 non-responders to this schedule reacted favourably to COP. The results in 10 patients with immunocytic lymphomas were of a similar order. Better results were achieved in patients with germinal centre tumours: 9 out of the 11 patients with centrocytic lymphomas and all 20 patients with centrocytic-centroblastic tumours responded with a complete or partial remission. Of 18 patients with high-grade malignant lymphomas, 5 responded with a complete remission, 8 with a partial remission.

[T-cell lymphoma (author's transl)]. / T-Zell-Lymphome

The percentage of T- and B-lymphocytes was determined by means of surface markers in 190 patients suffering from various lymphoproliferative disease. Characteristic T-cell lymphomas were diagnosed in 8 patients: 2 of these patients suffered from acute leukaemia, 2 from lymphoblastic lymphoma, 3 from mycosis fungoides and one from the Sézary syndrome. The clinical course of the disease in these patients, the clinical picture and the results obtained with various surface markers and with unspecific mitogens are described and discussed.

[T-lymphocytes and their function in Hodgkin's disease]. / T-Lymphozyten und ihre Funktion beim M. Hodgkin.

In untreated patients with Hodgkin's disease the percentage of T-lymphocytes was significantly reduced in comparison to healthy controls independent of the stage of the disease. The absolute number of T-lymphocytes was also reduced in most patients. The response of lymphocytes after PHA-stimulation was diminished parallel with the skin reactivity: Normal results were obtained in early stages and with favorable histological types whilst low values were found in stages III and IV and in unfavourable histological types. A correlation between the percentage of T-lymphocytes and the PHA-stimulation was found in early stages, but not in stages III and IV. There was also a correlation between the absolute number of T-lymphocytes and skin reactivity. The percentage of DNA-synthesizing lymphocytes was significantly higher than in normal blood. The highest values were found in stages III and IV and in unfavourable histological types. After radiation therapy the T-lymphopenia, the diminished PHA-stimulation as well as anergy was more pronounced than after chemotherapy.

[Essential mixed cryoglobulinemia with kidney involvement]. / Essentielle gemischte Kryoglobulinämie mit Nierenbeteiligung

Essential mixed cryoglobulin associated with rapidly progressive glomerulonephritis has been observed in a 64-year-old patient. The cryoglobulin consisted of monoclonal IgM-kappa and polyclonal IgG and displayed rheumatoid-factor activity. The antinuclear antibody test was negative. In the immunofluorescent method renal biopsy showed positive staining for IgG; IgM and the early and late complement components. The rheumatoid factor activity of the renal IgM deposits was demonstrated by binding of fluorescent aggregated IgG. There is thus evidence that the vasculitis observed in essential mixed cryoglobulin is caused by IgM-IgG complexes. The differentiation of essential mixed cryoglobulin from lupus nephritis with cryoglobulins is discussed.

[Acute lymphatic leukaemia in children: re-examination after remission of at least five years (author's transl)]. / Akute lymphatische Leukämie im Kindesalter. Nachuntersuchungen nach einer Remissionsdauer von mindestens 5 Jahren.

Full remission of more than five years was observed in nine of 24 children with acute lymphatic leukaemia. They had been treated by a scheme similar to the Pinkel VII one, and all had been discharged from treatment. The immune status, bone marrow, radiological, neurological and psychosomatic studies, as well as various laboratory tests indicated that in seven of the children the findings, are essentially normal. But two children have lasting severe organ damage, portal fibrosis in one and bilateral intracerebral calcification in the other, both presumably due to the methotrexate treatment.

[Prolymphocytic and hairy cell leukemias as special forms of chronic lymphatic leukemia]. / Prolymphozytäre und Haarzellen-Leukämie als Sonderformen der chronischen lymphatischen Leukämie.

Cytochemical and immunological studies were performed on "hairy" cells from 5 patients. The results, primarily the detection of surface immunoglobulins after incubation in immunoglobulin-free medium support the hypothesis that hairy cells are B-cells. Further parameters for B-cell lineage are the failing suppression of unspecific esterases by NaF, the presence of tartrate-resistant acid phosphatase and the absence of phagocytic capacity and glass adherence (skin window). A lysozyme could not be demonstrated. Of two patients with prolymphocytic leukemia one was characterized as T- and one as B-cell leukemia. Therefore, the prolymphocytic leukemia has to be discussed as intermediate form of ALL and CLL. In both patients the therapeutic results were discouraging with cytostatics (e. g. chlorambucil), splenectomy is considered as the treatment of choice.

[Humoral and cellular immune mechanisms in venous occlusive lung diseases]. / Humorale und zelluläre Immunmechanismen bei veno-okklusiver Erkrankung der Lunge.

In a 73-year-old female patient, pulmonary veno-occlusive disease was diagnosed by the typical histological findings in the lung. Immunofluorescence studies showed granular deposits of IgG and C1q in the lung, suggesting immune complex deposition and complement activation by the classical pathway. Furthermore, the presence of lymphocytes sensitized against collagen was demonstrated using the leukocyte migration inhibition system. These results demonstrate the significance of humoral and cellular immune mechanisms in the pathogenesis of this disease.

[Differentiation of non-Hodgkin's lymphoma: immunological, cell-kinetic, and physical methods (author's transl)]. / Zur Differenzierung von Non-Hodgkin-Lymphomen.

Some aspects of division and cell density, expression and motility of certain surface structures were studied on lymphocytes of non-Hodgkin's lymphoma of high and low degrees of malignancy. The neoplastic lymphocytes of the two lymphoma types differed in these aspects.

Insoluble PHA- A B-cell mitogen in man?

Blood lymphocytes of normal individuals and of patients with chronic lymphocytic leukemia were evaluated for their blastogenic response to insoluble PHA. In at least preferential stimulation of normal B-lymphocytes was observed, whereas leukemic lymphocytes were almost insensitive. This result supports the hypothesis of a functionally defective B-lymphocyte population in chronic lymphocytic leukemia.

[Blast crisis in chronic myeloid leukemia. Results with vindesine and prednisolone]. / Blastenkrise der chronischen myeloischen Leukämie. Ergebnisse mit Vindesin-Prednisolon.

Nine patients with blast crises of chronic myeloid leukaemia were treated with a combination of vindesine and prednisolone. Vindesine, 2 mg/m2, was administered intravenously on two successive days each week and prednisolone, 60 mg/m2, orally once daily. Blast crises were divided into myeloblastic and lymphoblastic ones using cytochemical parameters as well as detection of terminal deoxynucleotidyl transferase. Complete remission was achieved in four patients, partial remission in one patient; in four patients treatment was unsuccessful. According to cytochemical findings, a therapeutic success was obtained in three of four patients with lymphoblastic and two of four patients with myeloblastic crises whereas no response to the treatment was seen in one patient with an undifferentiated type. Side effects of the therapy were frequent, but of only low degree and never led to interruption of treatment. On the basis of these results and from experience reported in the literature, the combination of vindesine and prednisolone can be recommended as the therapy of choice in blast crises of chronic myeloid leukaemia.

[A method for the detection of suppressor lymphocytes and its clinical use]. / Eine Methode zum Nachweis von Suppressorlymphozyten und ihre klinische Anwendung.

Suppressor cells play a major role in immune regulation and supervision. Unspecific suppressor cells can be stimulated by Concanavalin A (ConA) in a concentration of 1-50 micrograms/ml. Absorbed pooled human AB serum is the optimal serum source. Monocytes are necessary to induce suppressor cells. Preincubation of lymphocytes abolishes the suppressor cell inducibility. Different ConA incubation periods show two suppressor peaks, the first on day 0-1, the second on day 4-6. It is concluded, therefore, that we deal with two populations of suppressor cells. The first of these seems to resemble the spontaneous in vivo suppressor level, needs not to be activated by ConA but is rapidly inactivated without permanent antigeneic stimulus. The second peak consists of suppressor cells which are activated by a ConA stimulation of at least 3-4 days. Another conclusion can be drawn from these data: The conventional control system for the ConA induction of suppressor cells is not the optimal one, because the spontaneous suppressor cells are not included within this system, although they perhaps give a better insight into the actual immune status.