Klaus Abbrederis

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine

&NA; In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty‐eight in‐patients with cancer pain received a short‐term infusion lasting 2–42 days, and 8 out‐patients underwent long‐term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P < 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5–48 mg (median 19 mg) of morphine was required daily, significantly (P < 0.001) less than the 10–90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long‐term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low‐dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: Results of the austrian multicenter phase II study

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNalpha) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m2, following an initial reduction of WBC to less than 20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in 3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNalpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

SummaryWe investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1–2×106 units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

A randomized study comparing interferon (IFNα) 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.

Interferon-α 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)a-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 ]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 IFNa 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 IFNa alone or in combination with LD ara-C or HU.

Acute lymphocytic leukemia. Cytochemistry and ultrastructure.

SummaryCytochemical methods allow the distinction of a peculiar-PAS and β-glucuronidase positive-type of acute leukemia, which, according to previous authors, is termed acute lymphocytic leukemia (ALL). The cytochemical pattern suggests poor differentiation, which is confirmed by electron microscopic investigations. Degenerating mitochondria seem to be peculiar for this cytological type of acute leukemia. The special clinical features observed in ALL in adults include a distinctly better prognosis, a special sensitivity towards Vincristin, L-asparaginase, and glucocorticoids as well as the tendency to develop leukemic meningosis.ZusammenfassungAuf Grund zytochemischer Untersuchungen läßt sich ein besonderer-PAS- und β-Glukuronidase-positiver-Typ unreifzelliger Leukämien abgrenzen, der auch als akute lymphatische Leukämie bezeichnet wird (ALL). Das zytochemische Muster, ebenso wie die elektronenmikroskopische Erscheinung, sprechen für eine geringe zytologische Differenzierung. Degenerationsformen der Mitochondrien scheinen für die ALL typisch. Klinische Besonderheiten dieser Leukämieform betreffen eine deutlich bessere Prognose und eine besondere Empfindlichkeit gegenüber Vincristin, L-Asparaginase und Glukokortikoiden und die Neigung zur Ausbildung einer Meningosis leukaemica.

Die Differenzierung menschlicher Blutlymphozyten mit immunologischen Methoden

In 47 patients with acute lymphoblastic leukemia surface markers were evaluated on mononuclear cells of the peripheral blood as well as in some cases on bone marrow lymphocytes. The lymphocytes were characterized by their binding capacity for sheep red blood cells, the demonstration of Fc-receptors, complement receptors as well as surface immunoglobulins. In 6 of 23 untreated patients the blasts bound sheep red blood cells spontaneously (T-ALL), in two of these six cases the lymphoblasts had simultaneously receptors for complement. In a further patients the lymphoblasts had complement- and Fc-receptors. The blasts of 16 of 23 patients were negative in respect to the markers tested (O-ALL). By comparing two groups of patients--one with positive cells, one unreactive--the clinical features differed: the marker positive group showed a predominance of male patients, 5 of 7 patients had a massive mediastinal mass and the remission rate was lower than in the group with positive blasts. 24 patients in remission under maintance treatment had a decreased percentage of rosette forming lymphocytes as well as lymphocytes with surface immunoglobulins and Fc-receptors. There existed some correlation between the percentage of rosette forming lymphocytes and the clinical course: patients with complications had lower percentages of rosette forming lymphocytes than patients with a favourable course.

Unreifzellige Leukämien im fortgeschrittenen Lebensalter

SummaryWe conducted an investigation of 186 randomly selected acute adult leukemia patients in order to examine how far age and subtype of leukemia can be correlated with survival rate. The diagnosis of leukemia was established by cytochemical and cytomorphological techniques. There was an increased frequency of acute myelogenic leukemias in older patients. The age group of the 61–90 year old showed a significant decrease in the survival rate, but at the same time in this age group there was a higher frequency of leukemia types with poor prognosis. Early deaths were correlated with advanced age of patients. There were no long time survivors (with survival rates longer than 4 years after diagnosis) above the age of 57.

Zur Typenverteilung, Alters- und Geschlechtsdisposition der akuten Leukämien des Erwachsenen

Zusammenfassung204 Fälle akuter Leukämien bei Erwachsenen wurden zytochemisch untersucht und klassifiziert. 48,5% davon waren akute myeloische Leukämien. Auf die akute lymphatische Leukämie entfielen 12,3%, auf die Monozytenleukämie 10,8%, auf die Promyelozytenleukämie 9,3%, auf undifferenzierte Formen 8,8% und auf die myelomonozytäre Leukämie 6,4%. Der Rest waren seltene Formen. 58,9% der Patienten waren männlichen, 41,1% weiblichen Geschlechts. Besondere Geschlechtsdispositionen wiesen die akute lymphatische Leukämie (72% Männer, 28% Frauen) und die Monozytenleukämie (33% Männer, 67% Frauen) auf. Die akute lymphatische Leukämie erwies sich vor allem als Erkrankung des jugendlichen Erwachsenen, die akute myeloische und besonders die Monozyten- und die myelomonozytäre Leukämie traten hauptsächlich im höheren Alter auf. Bei Beurteilung des Therapieerfolges muß dies berücksichtigt werden.Summary204 cases of acute leukemia of adults have been investigated cytochemically and classified. 48,5% were identified as acute myeloid leukemia. Except a few patients with rather rare cytological forms of leukemia 12.3% of the cases were classified as acute lymphatic leukemia, 10.8% as monocytic, 9.3% as promyelocytic, 8.8% of the patients had cytochemically undifferentiated and 6.4% had mixed myelomonocytic forms of leukemia. 58.9% of the patients were of male, 41.1% of female sex. Special sex disposition was observed in acute lymphatic leukemia (72% male, 28% female) and in monocytic leukemia (33% male, 67% female). Among all cytological forms of acute leukemia the highest incidence was found in the age range of 60 to 70 years. In contrast the highest frequency of acute lymphatic leukemia was observed among young people (20 to 30 years). Acute myeloid and especially monocytic and myelomonocytic leukemias are mainly found among patients of 50 to 70 years of age.

Cytochemische Untersuchungen an den Rundzelleninfiltraten bei chronischen oder protrahiert verlaufenden Virus-Hepatitiden

ZusammenfassungIn den „Rundzelleninfiltraten“ bei chronischen und persistierenden Hepatitiden läßt sich auf Grund histochemischer Untersuchungen (unspezifische Esterase mit Naphthol-AS-Acetat mit und ohne NaF-Hemmung, saure und alkalische Phosphatase, Naphthol-AS-D-Chloroacetat-Esterase, Sudanschwarz B-Färbung, Perjodsäure-Schiff-Reaktion (PAS) und Methylgrün-Pyronin-Färbung) folgender Befund erheben: In den Zentren der entzündlichen Infiltrate liegen Ansammlungen von Lymphocyten, welche den hauptanteil der Infiltrate ausmachen. Die Infiltrate wachsen peripher durch eine Abschmelzung von Leberzellen. Die v. Kupfferschen Zellen bleiben bestehen und werden in die Randbezirke der Infiltrate einbezogen. In diesen Bezirken finden sich häufig auch einige Neutrophile und wenige Monocyten. Auch Plasmazellen lassen sich überwiegend in diesen Bereichen nachweisen. Schließlich können noch Venolen und Gallecapillaren identifiziert werden. Eine Beteiligung von Fibroblasten läßt sich nicht sicher erfassen.SummaryInvestigations on the cellular composition of “round cell infiltrates” of the liver in chronic and persistent hepatitis were performed using various histochemical methods. (Nonspecific esterase using naphthol-AS-acetate as substrate with and without added NaF, naphthol-AS-D-chloroacetate-esterase, acid and alkaline phosphatase, Sudanblack B-stain, periodic acid-Schiff reaction and methylgreen-pyroninstain.) The following results were obtained: The central parts of the infiltrates are mainly composed by small round cells exhibiting a cytochemical pattern similar to that of lymphocytes. The infiltrates enlarge by peripheral growth replacing necrotic acinar cells; the v. Kupffer cells persist and are included in the peripheral parts of the infiltrates. In these regions few neutrophils and rarely monocytes are seen. Plasma cells are also mainly localized in this region. Many venoles and biliary ductuli were identified within the infiltrates. The methods used did not permit an unequivocal identification of the role of the fibroblasts in infiltrate formation.