Due to eligibility criteria not all patients with the disease under investigation can be recruited for therapeutic studies. Thus, the external validity of study results cannot per se be taken for granted. The representativity of the admitted patients is the most relevant determinant for external validity and has to be assessed. As an example we examined the representativity of the patients recruited for the German multicenter study group for adult acute lymphoblastic leukemia (ALL) (GMALL). Lacking nationwide ALL incidence figures available in Germany, a methodology was developed to estimate incidence figures, too. All relevant study groups, hospitals, and diagnostic labs were asked to provide data about patients with ALL newly diagnosed between 1997 and 1998. A matching procedure was developed, as heterogeneous databases had to be pooled and checked for duplicates. Age- and sex-specific incidences of ALL were estimated and compared with the number of patients recruited for the GMALL in the same time period. The purpose was to develop a methodology for estimating incidence figures and evaluating the representativity of patients of the GMALL. The combination of various data sources allowed estimation of reliable incidence data for ALL in Germany. Comparisons with the incidence figures for ALL in other countries and crosschecks within Germany confirm our results. Sixty-two percent of all ALL patients in Germany were admitted to the GMALL study. The recruitment rate of more than 60% of the annual incidence of ALL to the GMALL suggests a high external validity as well as an impact of the study on the patterns of treatment and referral of ALL in adults in Germany. There is no selection bias of patients admitted to the GMALL compared to those patients not included in the study.

Die akute lymphatische Leukämie macht etwa 20% der akuten Leukämien des Erwachsenenalters aus. Die Gesamtinzidenz liegt bei 3–4 Fällen/100.000 pro Jahr wobei der Häufigkeitsgipfel im Alter unter 10 Jahren liegt. Die Symptome der ALL sind eher unspezifisch und resultieren meist aus der Durchsetzung des Knochenmarks mit unreifen lymphatischen Blasten und der entsprechenden Suppression der normalen Hämatopoese. Alle anderen Organe können jedoch ebenfalls einen leukämischen Befall aufweisen. Obwohl in den meisten Fällen lymphatische Blasten im Differenzialblutbild erkennbar sind, ist eine Knochenmarkpunktion mit entsprechenden Spezialuntersuchungen für den Ausschluss bzw. die Bestätigung einer ALL unverzichtbar. In den vergangenen Jahrzehnten wurden erhebliche Fortschritte bei der Behandlung der ALL gemacht und sie gehört zu den wenigen disseminierten malignen Erkrankungen, die allein durch Chemotherapie geheilt werden können. Die Heilungsrate konnte von <10% vor 1980 auf nunmehr 30–40% verbessert werden. Der folgende Artikel bietet eine Übersicht über aktuelle diagnostische Verfahren, therapeutische Möglichkeiten, einschließlich der Stammzelltransplantation, über Prognosefaktoren und gibt einen Ausblick auf zukünftige Konzepte für Diagnostik und Therapie.

The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients.

Substantial progress in immunological and molecular analyses has now enabled most cases of acute leukemia to be classified as myeloid or lymphoid differentiated neoplasms [1]. In spite of these sophisticated methods, which have completed routine morphological and cytochemical studies, a certain number of acute leukemias remain unclassified [2]. This group of acute undifferentiated leukemias, mostly referred to as AULs or null-AL(L)s, can be characterized by the absence of morphological and cytochemical features for myelomonocytic differentiation at light microscopic level, lack of reactivity with anti-T-cell antibodies (Leu-1, OKT 11), and negativity for expression of the CD 10 antigen or cytoplasmic or surface immunoglobulin [3]. Some of these leukemias display myeloid surface antigens, alone or together with early B- or T-lymphoid surface markers, suggesting myeloid or bilineage differentiation [4]. It still remains unclear, however, whether these myeloid markers reflect true myeloid differentiation or are due to aberrant marker expression [5].

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.

Ein Überblick einschlägiger Therapiestudien bei AML des Erwachsenen zeigt keine durchbruchartigen, wegweisenden Therapiefortschritte in den 80er Jahren. Diese liegen bereits in den 70er Jahren, etwa bei einigen wirksamen Induktionsregimen. Fortschritte in diesem Jahrzehnt sind nur in kleinen Schritten zu erwarten. Der klinischen Forschung obliegt es, die einzelnen Therapiekomponenten und neue Elemente sorgfältig auf ihre Wirksamkeit zu prüfen, um diese besser additiv einsetzen zu können. Eine Standardisierung der Therapie ist dabei unumgänglich, vielfach auch ein randomisierter Vergleich. So konnte in unserer multizentrischen Studie erstmals die Rolle der monatlichen Erhaltungstherapie geklärt werden. Ebenso konnte eine bessere Beurteilung einer speziellen Immuntherapie ermöglicht werden.

Analyses of the cellular DNA content were carried out in 446 patients with newly diagnosed acute myeloid (AML) and lymphoblastic (ALL) leukemias in order to assess the frequency of DNA aneuploidies and its relation to immunologic and morphologic subtypes as well as its prognostic relevance. Based on high resolution FCM analyses and standardized reference measurements, DNA aneuploidies were identified at a similar frequency in children and adults with AML (38.0% and 40.0%) and ALL (40.0% and 37.4%). In AML aneuploid DNA stemlines were significantly less frequent in FAB-M 1 cases as compared to the other morphologic subtypes (p less than 0.05), whereas the degree of DNA aneuploidy was significantly lower in M 1 and M 2 leukemias as compared to the M 4 and M 5 subgroups (p less than 0.05). In ALL non-T/non-B and C-ALL revealed a higher frequency of DNA aneuploidies than T- and Null-ALL cases (p less than 0.05). No differences in the response to induction therapy were found between patients with and without DNA aneuploidy in children or adults with AML or ALL. In the childhood ALL trial BFM 79/81, however, a significantly higher frequency of long term remissions was observed in children with DNA aneuploidy (0.91 versus 0.66 at five years, p = 0.053). A similar though not significant tendency was also revealed from the AML studies BFM 78 in children and 78/81 in adults. In the subsequent studies these differences could not be confirmed at present, possibly because of the considerably shorter observation time.

The number of antibody molecules on individual erythrocytes was counted in A1, A2, A3 B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A1. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A1>A2>Ax>A3B. When compared to the average for total A1 adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A1 adult red cells was 5.6±3×104, while A2 had 0.85±0.35×104 molecules, thus showing a significant quantitative variation.

In 1978 a study group was formed in the Federal Republic of Germany for the treatment of acute lymphoblastic leukemia (ALL) und acute undifferentiated leukemia (AUL) in adults. A modified form of an intensive induction and consolidation regimen successful in children with ALL [1] was used. The objective was to determine whether a prolonged remission induction and the addition of the drugs cyclophosphamide, cytosine-arabinoside and 6-mercaptopurine to the more conventional drugs for induction therapy of ALL, vincristine, prednisone, daunorubicin and L-asparaginase would improve the longterm results. It was hoped that a large number of hospitals would participate and that, with a sufficient number of patients uniformly treated, it would be possible to determine prognostic factors and to identify risk groups. This report concerns the design of the study, the toxicity of the therapeutic regimen and the first results.