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Grundlagen: Ziel der Studie war es, die Raten und Qualität an Remissionen durch den primären Einsatz einer Purinantagonistentherapie sowie deren Dauer oder Verlängerung durch eine Interferonerhaltungstherapie bei B-CLL-Patienten zu bestimmen, Zudem sollten Verträglichkeit und langfristige Behandlungsergebnisse (Zeit bis zur Wiederbehandlung, progressionsfreies Überleben und Gesamtüberleben) bestimmt werden. Methodik: In einer multizentrischen Phase-II-Studie wurden zwischen 1995 und 2001 74 Patienten mit B CLL mit 6 Zyklen Fludarabin (25 mg/m² iv x5d q28d, x6) und anschließend Intron-A Erhaltungstherapie (3x3 MU/w durch 1 Jahr) behandelt. Die Einschleusungskriterien umfaßten weitgehend die Behandlungsindikationen nach den NCI-Kriterien, die Remissionsbeurteilung erfolgte nach den NCI-Kriterien von 1988 bzw. 1996 unter Einschluß von Ultraschall, CT und Knochenmarksuntersuchung. 73% der Patienten waren chemonaive, 24% hatten ≤2 Regime an Vorbehandlung (unter Ausschluß anthrazyklinhältiger Medikation) erhalten. Ergebnisse: Bei chemonaiven Patienten konnte in 20,8% eine CR, in 6,3% eine PRnod und in 50% eine PR erzielt werden. Die CR- und Gesamt-Remissions-Rate waren mit jener vorbehandelter Patienten (CR 18,8%) vergleichbar. Im Gegensatz dazu konnte bei Patienten mit Resistenz oder im Relaps nach Remission auf Fludarabin mit einer weiteren Chemotherapie nur mehr in 57% eine Remission und in keinem Fall eine CR erreicht werden. Das beste Ansprechen auf die Behandlung war im peripheren Blut, der geringste Response in Milz und Knochenmark zu beobachten. Mittlere Responsedauer, TTF und Zeit bis zur Wiederbehandlung betrugen 19,6, 23,4 , und 36,9 Monate. Das mediane Überleben ist noch nicht erreicht (mittleres Überleben: 44,1 Monate). Schlußfolgerungen: Angesichts der bestehenden Vorbehandlung bei etwa einem Viertel der Patienten sowie der Verwendung sensitiver Diagnostik (NCI 1996) können die Remissions-und CR-Raten als zufriedenstellend und die durch die Kombination mit Fludara und Intron-A erzielten Intervalle bis zur Wiederbehandlung als gut bezeichnet werden. Das Konzept der Präservation der Lebensqualität unter gleichzeitigem Versuch der Remissionserhöhung/Verlängerung wird in einer Studie mit oralem Fludara und Intron-A als Nachfolgeprotokoll ab Frühjahr 2001 weiterverfolgt. [ABSTRACT FROM AUTHOR]

Grundlagen: Für die adäquate Anwendung von anti-CD20-Anti-körper(Mabthera)-Therapien bei CLL stellen die Findung klinisch tolerabler Dosierungsschemata und die Aufklärung der Wirkprinzipien Voraussetzungen für eine erfolgreiche Mono-, aber auch rational begründete Kombinationstherapie dar. Methodik: In einer monozentrischen Phase-I/II-Studie wurden Patienten mit therapierefraktärer B CLL und Behandlungspflicht nach den NCI-Kriterien mit Mabthera in einschleichender und subsequent progressiv gesteigerter Dosierung behandelt. In Parallele zur Analyse der klinischen Wirksamkeit wurden Analysen zum Mechanismus der Wirkung durchgeführt: Ergebnisse: 1) Lymphozytenkinetik im Blut (PBL): Alle Patienten zeigten über den Verlauf von 6wöchentlichen Behandlungszyklen eine deutliche Reduktion der Gesamtleukozyten (100 + 19G/L vs. 32 + 10 G/L). Der maximale zytoreduktive Effekt war während aller Zyklen innerhalb 1h zu beobachten (delta: 44,8+16,2), während innerhalb von 24 h eine partielle Erholung der Leukozytenzahl eintrat (delta +30%). 2) CD20-Expression und Bindung von Mabthera: Basale CD20-Expression, Bindung von Mabthera und Veränderung der CD20-Expression unter Behandlung wurden mit Antikörpern gegen CD20-Oberflächenepitop, murines FAB-Fragment und intrazytoplasmatisches CD20-Epitop in IF-Doppelfärbungen bzw. Western Blot bestimmt. Dabei konnten im 1. Zyklus in vitro, nicht aber in vivo progrediente Beladbarkeit der CLL-Zellen mit Mabthera sowie Abnahme der intrazytoplasmatischen CD20-Färbung nachgewiesen werden. Im Gegensatz zur Erholung der Leukozytenzahl war in 24 h kein rescue der CD20-Expression peripherer B-Zellen nachweisbar. 3) Biologische Auswirkungen der Mabthera-Behandlung: Triple-Färbungen mit PI/AnnexinV und CD19 belegen die Induktion von Apoptose parallel zur Elimination der Leukozytenzahlen im PBL. Schlußfolgerungen: Auch unter geringsten in vivo Dosen von Mabthera (50 mg/m²) treten in 1 h massive Reduktionen der Lymphozyten und Induktion von Apoptose und in 24-h-Dissoziation von CD20-Expression und der Lymphozytenkinetik auf. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).

A patient is reported with a history of several years of chronic urticaria, transient fever, arthralgias and secondary systemic amyloidosis. A biopsy of an urticarial lesion showed necrotizing vasculitis and amyloid deposits in the eccrine sweat glands. Amyloid A deposits were also detected in kidney and rectum biopsies. This patient is likely to represent a variant of the Muckle-Wells syndrome (chronic relapsing urticaria, fever, arthralgia, deafness and renal amyloidosis). Hitherto undescribed is the presence of a necrotizing vasculitis as cause of the urticarial rash; further investigation will determine whether or not this finding represents the rule rather than an exception.

Proto-oncogenes, the normal equivalents to the transforming genes of mammalian tumorigenic retroviruses, are implicated in essential biological processes of normal human cells, like differentiation and proliferation. In vivo and in vitro studies clearly demonstrate that activation of proto-oncogenes with subsequent transformation in tumorigenic oncogenes plays an important role in induction and acceleration of the malignant disease, and also determines metastatic spread and development of resistance to chemotherapy in certain neoplasias. Investigation of these genes and analysis of their activation state should routinely be introduced in staging of hematological neoplasias, thus contributing to refinement of histopathological classification, clearer discrimination between reactive and neoplastic conditions and understanding of pathophysiological processes. Furthermore, impact on definition of high risk patients and novel therapeutic concepts based on a better definition of tumour biology may be expected from these studies. "Molecular cytology" combines detection of oncogenetic mRNA and the relevant oncoprotein on the single cell level by using "mRNA-in situ hybridization" and immuno-histochemistry. Application of this technique will allow to determine the mechanisms regulating the expression of oncogenes to define functional heterogeneity of tumour cell subsets and to clarify the relevance of minimal residual disease.

The number and distribution of reactive cells in more than 100 non-Hodgkin lymphomas (NHL) were evaluated in situ in cryostat sections. The results were compared with histological and clinical findings. 40% of the T cell content of normal lymphatic tissues was found in tissues of B-cell NHL. This corresponds to a mean of 2 X 10(4) reactive T-cells/microliter tumour tissue. The numerical density of natural killer (NK) cells within tumours was similar to that of normal lymphatic tissues (0.5 X 10(4) cells/microliter). The distribution of the reactive cells within the tumours was diffuse except in the case of centroblastic/centrocytic lymphomas. On evaluation of the different histological entities a significant correlation was obtained between number of helper/inducer (TH) cells, TH:T-suppressor (Ts) ratio and prognostically favourable histological subgroups. Furthermore, independent of histological criteria, a close correlation was found between a high number of TH-cells, a high TH:Ts ratio and a favourable clinical course (p less than 0.04). NK-cell infiltration was present to a markedly higher extent in tissues of patients with generalized disease as compared with localized disease (p less than 0.03). Low-grade malignant NHL contained significantly more NK cells than high-grade malignant NHL, as was the case also in treated, as opposed to untreated patients. These findings together suggest that reactive cells influence tumour growth via local interactions. However, tissue distribution and infiltration density of T-cell subpopulations and NK cells were clearly different. Thus, in tumour tissues different and independent immunoregulatory mechanisms seem to be associated with these two lymphocyte subsets.

Rhabdomyolysis is usually known to the anaesthetist, who may be confronted with this acute, life-threatening complication during anaesthesia. However, also the medical specialist ought to be familiar with the clinical picture of malignant hyperthermia, since rhabdomyolysis may occur as a late post-anaesthetic complication. Even in oligo-symptomatic and protracted cases of malignant hyperthermia, the case history, electromyogram, exclusion of other possible causes of rhabdomyolysis and, if possible, muscle biopsy contribute to the confirmation of the diagnosis. If a muscle biopsy is not available then a platelet bioassay may substantiate the diagnosis.

Immunological markers important for the diagnosis of the following subtypes of Non-Hodgkin lymphomas (NHL) are discussed: lymphocytic lymphomas (i.e.: B-CLL, immunocytic NHL, prolymphocytic- and hairy cell leukemia), NHL derived from follicular center cells (centrocytic, centroblastic/centrocytic and centroblastic NHL), lymphomas with blastoid appearance (various forms of lymphoblastic and "large cell" NHL) and disorders of T lymphocytes (NHL) of peripheral T cells and T gamma lymphocytosis with neutropenia). In these disorders, the patterns of leukocyte surface antigens like T1 (CD5), Tac (CD25), CALLA (CD10), FMC7, Tü1 and Tü33 as well as staining for the terminal transferase (TdT) and of dendritic follicular cells have been examined by investigating specimens of a large group of patients. Apart from the diagnostical value, these evaluations have contributed to a better understanding of normal B cell differentiation whereas the role of marker studies as independent prognostic factors requires additional prognostic studies. Finally, the value of immunoperoxidase or alkaline phosphatase staining of cryostat sections of bone marrow biopsies is emphasized, which allowed the diagnosis and classification of 74% of 92 NHL studied by this technique.