The myelodysplastic syndromes pose important clinical and scientific chal lenges which in recent years have attracted growing interest within haemato oncology and molecular genetics. Their potential as a model for the study of human leukaemogenesis makes this one of the most exciting fields in contemporary haematology. Rapid progress towards understanding these disorders had created the need for international interdisciplinary communi cation. In order to fulfil this need the First International Symposium on Myelodysplastic Syndromes was organized in Innsbruck, Austria, in June 1988. The substantial number of excellent speakers and of participants manifested the great international interest on the topic. The present volume consists of the contributions of most of the speakers at this Symposium. We wish to thank all those who submitted their manus cripts. G. ]. Mufti Franz Schmalzl Contents Classification and Cytopathology of Myelodysplastic Syndromes The Classification of Myelodysplastic Syndromes J. M. Bennett . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Classification of Myelodysplastic Syndromes in Clinical Practice: of Subtypes Frequency G. Flandrin . . . . . . . . . . . . .: . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Pathogenesis of Anaemia in the Myelodysplastic Syndrome A. Jacobs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Immunological Abnormalities in the Myelodysplastic Syndrome T. J. Hamblin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Pediatric Experiences in Myelodysplastic Syndrome H. Gadner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Myelodysplastic Syndromes in Childhood: Description of 11 Cases E. T. van't Veer-Korthof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 The Value of Cytochemical Investigations in the Diagnosis of the Myelodysplastic Syndromes F. Schmalzl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Enzyme Cytochemical Studies in Myelodysplastic Syndromes A. De Pasquale and D. Quaglino . . . . . . . . . . . . . . . . . . . . . . . . ."

Die j{hrlichen H{mophilie-Symposien befassen sich mit neuen Erkenntnissen aus der Grundlagenforschung und Klinik der H{- mophilie, verwandter angeborener und erworbener Blutungs- krankheiten und thrombophiler Diathesen. Diese Veranstaltun- gen verfolgen das Ziel, unter Mitwirkung kompetenter Modera- toren und Referenten aller involvierten Fachdisziplinen, [rzten und Wissenschaftler aus dem zentraleurop{ischen Raum aktuelle Erkenntnisse und Erfahrungen zu vermitteln und eine stetige Verbesserung der Krankenversorgung zu bewirken. Die Hauptthemen des vorliegenden Bandes sind auf therapiebe- dingte Gef{hrdungendurch Virusinfektionen und nicht-infek- ti|se Nebenwirkungen gerinnungsaktiver Plasmapr{parate ge- richtet. Im Vordergrund stehen dabei H{ufigkeit, Verlauf, Verh}tung und Therapie der HIV-Infektion, H{ufigkeit und Verh}tung der Hepatitis B- und C-Infektion sowie Behand- lungswege der Hemmk|rperh{mophilie. In weiteren Hauptthemen werden angeborene bzw. heredit{re thrombophile Diathesen, insbesondere Protein C- und Antithrombin III-Mangelzust{nde sowie neue, vor allem molekularbiologische Fortschritte in der h{mostaseologischen Diagnostik verhandelt. Den Abschlu~ bildet eine Serie freier Vortr{ge }ber spezielle klinische Probleme bei angeborenenund erworbenen H{mostasest|rungen.

To give an update in the field of haemostasis scientists and clinicians fromoverseas and European countries met to dis- cuss the new trends in pathophysiology and clinical impli- cations. This book is devoted to the interactions of endo- thelial functions, tissue factors, coagulation inhibitors and haemostasis as well as detection and prophylaxis of thromboembolism. Data are presented of significant new re- search work on molecular and clinical approaches to diseases in haemostasis.

The clinical and experimental effects of cytokines have been realized for a long time. The clinical effects of tumor necrosis factor were noted almost 100 years ago. The basic biological effects of interferons and the hemopoietic growth factors have been known for more than 20 years. Given the basis of modern molecular biotechniques, information concern ing the mediators of cellular interactions is expanding almost exponentially. New principles in the regulation of cell growth, microenvironment, immune response, and malignancy are being discoverd right now. New therapeutic options are becoming available and have, in some areas, already crossed the threshold of clinical application. However, the way forward might be more complicated than we are in a position to recognize today. Some of the first optimistic expectations have not yet been fulfilled. Nevertheless, we are experiencing a revolution in medicine. To contribute to this process and to stimulate scientific communi in this field, we have initiated the international symposia on cytokines cation in hemopoiesis, oncology and aids. Major contributions from the first sym posium are published in this book. We thank all the authors for their contri butions, particularly those from the Hannover Medical School, who have worked hard to realize the congress and prepare these proceedings. We also thank the pharmaceutical companies whose support made this book possible. Finally we thank Professors Deicher, Poliwoda, and Riehm, heads of the Departments of Hematology and Oncology, Immunology, and Pediatric Hematology and Oncology, respectively, who encouraged us and gave us their firm support."

Since the introduction of new anthracycline derivatives and anthrachi none analogues a few years ago, aclacinomycin A (Aclarubicin) has become an established agent for the treatment of hematologic malig nancies. A special symposium was therefore held during the congress of the German Society of Hermatology and Oncology in Hannover in October 1989 to provide an up-to-date overv.iew. Leading experts from the United States, Sweden, and Germany reported on the results being obtained with aclacinomycin A, alone or combined with other agents, in patients with acute leukemias and myelodysplastic syndromes. This book is based on their contributions. As regards single-agent treatment, aclacinomycin A in myelodys plastic syndromes is dealt with, as well as its application in older patients with acute myeloid leukemia. Four contributions are devoted to the use of aclacinomycin A in combination with conventional or intermediate dose cytosine arabinoside or etoposide in patients with relapsed or refractory acute myeloid leukemia. The results reported indicate that aclacinomycin A has substantial activity in the treatment of hematologic malignancies. In summary, this book provides a valuable update on the current status of aclacinomycin A as used by experts in the treatment of he matologic malignancies."

The third volume of "Advances in Forensic Haemogenetics" contains the th scientific contributions presented at the 13 Congress of the International Society for Forensic Haemogenetics, held on October 19-21, 1989 in New Orleans, USA. The conference was organized and chaired by Dr. Herbert Polesky from Minneapolis. He and the local organizing committee which consisted of our friends and colleagues (J. Soubrada, L.R.Bryant, Dale D.Dykes, Ch.Harrison, P.Newall and R. Walker) deserve the thanks of our Society for a very successful meeting. Herb Polesky has also contributed a great deal to the preparation of this book. The contributions to the conference covered all fields of forensic haemo genetics, but an outstanding highlight of this conference was the application ofDNA-polymorphisms to paternity and to the identification of stains. This included basic lectures on biostatistical approaches as well as on molecular biology and many new technical approaches to our general and special aims. Forensic haemogenetics has now merged into a new discipline without having lost its original identity. On behalf of the Executive Committee of our Society I would like to extend my thanks to the authors of the articles contained in this book and to Springer-Verlag for having made such a quick publication possible. The volume should give the reader a picture of the state of the art and a survey of the most recent developments in the field of forensic and general haemo genetics.

Acute leukemia a quite homogenous disease failed to break through the sound barriere of when untreated reveals a substantial hetero unsatisfactory cure rates even in special sub geneity in its response to therapy. While cure groups. While new protocols including more is achieved in a certain proportion of pa effective supportive care show some increase tients other cases prove to be highly resis in the initial response rates and certain im tant. The curability is superior in acute provements in the long-term results, no ben lymphoblastic (ALL) than in acute myeloid eficial effect on the relapse rate during the (AML) leukemia and - within both type- first 1 Y2 years emerged from any of these higher in children as compared to adults. regimens. Thus, high chances for cure are The two age groups and cell types can be presently restricted to children with ALL further subdivided into prognostic groups and to lesser proportions children with by special diagnostic features. Thus, in AML and adults with ALL and AML.

You see things, and sa)' why? But I dream 1hings that never were, and I say, 11'hy 110t? George Bernhard Shaw Far ahead of his time, June 1st, 1909, Alexander Maximov communicated in a lecture, given in the Charite in Berlin, the fundamental knowledge, that there exists a lymphoid hemopoetic stem cell. Alexander Friedenstein explained that during the following years, Maximov also showed that the idea of interaction between hemopoetic cells and their stroma to be one of the most significant experiences. Monoclonal antibodies, recombinant DNA technics and the improvement of tissue culture models are the major developments to improve our possibilities to clarify growth and differentiation functions of hemopoetic cells. During the last two decades it was shown that soluble products, released from T cells, were not only involved in inducing B cells to produce specific immunoglobulin secretion after antigen stimulation. Furthermore, lymphokines together with other cytokines regulate the growth and differentiation of hemopoetic cells. As I have learned from Dick Gershon, our knowledge of the cellular basis for immunoregulation has come a long way since 450 B.C. Thucydides comments on the possible role of immune response in controlling the Black Death. Dick Gershon speculated that no scientific interest for these interesting observations was put forth at that time. Perhaps the problems, the Athenians were having with the Spartans, converted money from basis research into the military budget.

It is usual to associate megaloblastic anemia with folate or cobalamin deficien- cies. However, this notion, even if true in most cases, is too restricted. Megalo- blastosis in blood may also be observed in blood diseases without vitamin defi- ciency, and also after treatment with certain antineoplastic agents; in these con- ditions, the mechanisms vary with the etiology. On the other hand, folate or cobalamin deficiency may induce various clinical or biochemical disturbances without - as yet - macrocytic megaloblastic anemia. That the biochemical basis of megaloblastosis is the same in folate and cobal- amin deficiencies is due to the close metabolic interrelationships between thse two vitamins. However, the role of cobalamin deficiency in folate metabolism is still a matter of debate. Morphological abnormalities such as macrocytosis in peripheral blood and megablastosis in bone marrow, long considered to be the best indices of vitamin deficiency, are not always constant. Indeed, the improved diagnostic methods often lead to an early diagnosis of deficiency before the appearance of the usual hematological abnormalities.

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Publication of papers presented at the 12th International Meeting for Forensic Haemogentics Wien 1987. Topics covered included: Formal genetics, population genetics, biochemistry and serology of nearly all hereditary blood group poly- morphisms. Also several reviews of e.g. enzyme polymor- phisms; problems and aspects of the application for paternity testing; extensive articles on forensic stain information with numerous new methods and description of artifacts; polymorphisms in body fluids; quality control methods; use of biostatistics in forensic haemogentics.

For the first time, the proceedings of our biennial congress of the Society for Forensic Haemogenetics will be published by Springer-Verlag Berlin Heidelberg New York. The different areas of research now include cellu- lar allotypes, i. e. not only the traditional red cell antigens, but also those of white cells and platelets. Plasma isoproteins and intracellular isoenzy- mes, DNA polymorphisms (restriction length fragment and banding), and biostatistics are further topics in our Society. They also deserve our special attention in the future. The practical applications comprise paren- tage testing, stain analysis, population genetics, molecular biology and other immunogenetic aspects. The 11th Congress in Copenhagen was an excellent opportunity to pre- sent our broad spectrum of scientific activities at an international forum. Among the many outstanding lectures from different parts of the world, D. A. Hopkinson's contribution on genetic variation of human enzymes and H. Matsumoto's lecture on immunoglobulin allotypes in China should be mentioned here and also L. Bolund's communication on DNA. An optimal exchange of scientific information was achieved by the arrangement of main lectures, poster sessions and workshops. The Con- gress president Dr. Klavs Henningsen deserves our special thanks for his efforts in the excellent organization of this congress.

Chromosome abnormalities of cancer cells have been recognized for a long time, and have generally proven to be a highly specific marker ofmalignancy. The contri- butions collected in this book, "Tumor Aneuploidy", cover several major aspects of present knowledge conceming the occurrence and clinical significance of chromo- some abnormalities as delineated by karyotype analyses or measurements of the cellular DNA content. Certain non-random clonal chromosome losses, deletions and translocations ap- pear to represent primary genetic lesions of malignancies and reflect their clonal origin. Secondary intraneoplastic genetic evolution is suggested by major clonal ab- normalities of chromosome number and cellular DNA content. Both types of ge- netic changes have been reaching great relevance in cancer medicine, today. Although the Philadelphia chromosome was first discovered in chronic myelo- cytic leukemia (CML), by Nowell and Hungerford in 1960, new banding techniques developed in the 1970's were needed to identity this abnormality as a translocation between chromosomes 9 and 22 (t(9; 22)). Soon thereafter, further non-random translocations were detected and attributed to special diseases like t(8; 21) and t(15; 17) to acute myeloid leukemias (AML) and t(9; 22), t(4; 11), t(8; 14) to acute lymphoblastic leukemia (ALL).

Discovery and Relative Importance of Continuous Arteriovenous HemofIltration Lee W. Henderson Continuous arteriovenous hemofiltration (CAVH) has seen a brisk upswing in popularity in Europe since its introduction by Dr. Kramer and colleagues from Gottingen, West Germany in 1977 [1]. In the United States, the technique re- ceived approval as a clinical tool from the Food and Drug Administration in April 1982. This approval flowed, in no small measure, from the extensive expe- rience reported from Europe and in particular West Germany [e. g. , 2, 3]. Reports of its clinical utility now have begun to appear in the United States [4]. Removal of excess total body water using synthetic membranes in an extracor- poreal circuit dates back to the work of Alwall and the artificial kidney that he designed which permitted utilization of a hydrostatic pressure gradient to moti- vate water flow across the membrane [5]. Kolffs original rotating drum with its unencased membrane required an osmotic driving force [6]. Hemofiltration, the use of the filtration process to remove uremic solutes with the artificial kidney, in analogy with the glomerulus, was reported in 1967 [7]. This was made possible by the availability of synthetic membranes with far higher hydraulic permeability (approximately 10 times higher) than conventionally used cellulosic hemodialysis membrane. Specific applications of these "high flux" membranes to the removal primarily of excess total body water followed shortly thereafter [8].

H. J. Meiselman From the theoretical studies of Dr. Skalak, it is clear that white cells can significantly influence the pressure-time profile of a red cell/white cell suspen sion, and that the presence of even a small amount of relatively rigid white cells can have a profound effect on the filtration pressure during the latter portion of a filtration experiment. Conversely, white cell effects, regardless of their relative rigidity, are shown to have only minimal effects during the very early (i. e., 0-2 seconds) phases of the filtration process. Dr. Chien's experimental data support these theoretical studies, in that white cells of different mechan ical properties exhibit different pressure-time curves; pressure-time data for mixtures of leucocytes show shapes which can be predicted from the behavior of relatively homogeneous cell populations. The insensitivity of the very early portions of the filtration process to white cells is again reflected in the calculations made by Dr. Hanss. Using the nominal dilutions, white cell concentrations and the total volume of filtered cell suspension, he indicates that usually less than 1 pore out of 100 is liable to blockage by white cells. He thus concludes that, at the 1% accuracy level, initial filtration data should not be affected by mechanical pore blockage by white cells. Experimental studies by Dr. Lowe and Dr. Stuart question the WBC insensitivity of the early portion of the filtration process. Using a constant flow system, Dr."

Die Entwicklung neuer thrombolytisch wirksamer Medikamente einer- seits und ein rascher, auch technologisch bedingter Fortschritt moderner Gefasschirurgie andererseits sind notwendige Grunde, um den Wert der medikamentosen Thrombolyse erneut abzufragen. Der potentielle Nut- zen der Wiedereroffnung eines thrombotisch verschlossenen Gefasses muss in einem vertretbaren Verhaltnis zu den potentiellen Gefahren des Verfahrens stehen. Dabei hat sich gezeigt, dass die angiographisch erwie- sene Wiedereroffnung eines Gefasses u.V. nur ein vorubergehender Teil- erfolg ist und in die Beurteilung des Verfahrens unbedingt der langfristi- ge Nutzen, etwa die Haufigkeit postthrombotischer Syndrome oder die Letalitat nach Herzinfarkt, mit einbezogen werden mussen. Vnerlasslich ist daruber hinaus die Analyse der Komplikationen. Dieser Aufgabe hat sich eine Gruppe der auf diesem Gebiete erfah- rensten europaischen Kliniker gestellt und beim Deutschen Hamatolo- gen-Kongress 1983 in Munster in Vortragen und einem langfristig vorbe- reiteten Tischgesprach eine kritische Analyse der derzeitigen Situation gegeben. Vielleicht stellt dieses Buch eine Art abschliessender Wertung der ersten Generation von Thrombolytika - Streptokinase, Vrokinas- dar, wo die zweite Generation - Gewebe-Aktivatoren des fibrinolyti- schen Systems - eben in die klinische Erprobung eingefuhrt werden. Die Herausgeber sind den Autoren fur die konzise und kritische Dar- stellung ihrer Themen zu Dank verpflichtet.

In June 1984 a total of 169 physicians, scientists and students assembled in the now familiar and much-loved lair in the Wilsede Luneberg Heath near Hamburg, Germany, for the sixth biennial conference on Modern Trends in Human Leukaemia. This meeting, conducted by Prof. Rolf Neth in his own inimitable style, has established itself as one ofthe major events in the all too crowded programme of international conferences on leukaemia, cancer and related topics. Some may ponder why, with its "rustic" setting - flies, equine deposits, and lack of easy exit -, Wilsede has such an irresistible and persistent lure for so many of the world's top practitioners ofleukaemia research? The an- swer is, I suspect, a cocktail of Rolfs extraordinary charm, the pleasure of meeting friends and colleagues in a uniquely informal and relaxed atmo- sphere and the special style of the proceedings themselves, which focus on the evaluation of ideas and hypotheses rather than the cataloguing of data.

Almost a hundred years passed from the time of the first description of an intracranial aneurysm by Morgagni in 1761 to the year 1859, when Sir William Withey Gull arrived at the conclusion that haemorrhage in the subarachnoid space is caused by ruptured aneurysms. The introduction of lumbar puncture by Quincke 1891 and cerebral angiography by Moniz 1927 made it possible to establish the diagnosis of haemorrhage and its source. In recent decades the problems of treatment have come into prominence, first of all because of the inadequacy of conservative methods of treatment in most of the cases, and from surgical experience and its limitations which became apparent before very long. Because of the erratic development of neurosurgery and vascular surgery, above all, since the technique of microsurgery has been used, the entire removal of the source of haemorrhage has become a possibility, even though there were still quite different views taken regarding the most convenient time for surgical intervention, apart from the prevailing local conditions 134, 143, 144,261. In an up-to-date plan of treatment of subarachnoid haem orrhage (SAH) conservative measures are appropriate for bridging the pre-operative period, and must be considered the only solution in those cases in which the source of haemorrhage cannot be found. As far as the effectiveness of such conservative therapy is con cerned, the rate of re bleeding and the mortality provide sufficient comment.

Das Buch berichtet tiber das 1. Hauptthema der 28. Jahrestagung der Deutschen Gesellschaft flir Hamatologie und Onkologie 1983 in Mtinster. Der Zeitpunkt flir eine neue Bestandsaufnahme der Therapie der akuten Leukamien ist gtinstig, da ei- nige, in den 70er Jahren konzipierte Fortschritte inzwischen auf ausreichender Beobachtungszeit der behandelten Patienten beruhen. Die hier mitgeteilten und daB das diskutierten Ergebnisse aus maBgeblichen Zentren und Studien zeigen, Nahziel der kompletten Remission heute bei der Mehrzahl der Patienten zu er- reichen ist und daB dieses das Erreichen des Femziels Heilung flir einen Teil der Pa- tienten bedeutet. Dieser Teil erscheint bei lymphatischem Zelltyp groBer als bei myeloischem und innerhalb der Zelltypen bei Kindem groBer als bei Erwachsenen. Auf dem Weg bis hierher findet sich zunachst der therapeutische Durchbruch bei der Akuten Lymphatischen Leukamie des Kindes mittels Kombinations-Chemo- therapie und prophylaktischer antileukamischer Behandlung des Zentralnervensy- stems. Ihm folgten zahlreiche kleine Schritte der besseren Nutzung der verfligba- ren Chemotherapie durch ihre Intensivierung und Risiko-Anpassung. Parallel hier- zu wurde die Knochenmark-Transplantation hoch entwickelt. Die Immuntherapie fand konsequentere Formen. Wesentliche Altemativen und Modifikationen der Therapie akuter Leukamien befinden sich noch in Erprobung durch vergleichende Studien. Zuktinftiger Fortschritt ist zu sehen in einer Senkung der Frtihletalitat durch rechtzeitigen Therapiebeginn und verbesserte Supportivbehandlung, in der Entwicklung neuer, nicht kreuzresistenter Schemata zur Ausweich-Chemotherapie und ihre Einbeziehung in die primare Induktions- oder Konsolidierungs-Chemo- therapie, schlieBlich in der Erkennung von Risiko-Gruppen auch bei akuter mye- loischer Leukamie und einer Risiko-adaptierten Therapie oder Altemativ-Therapie.

In this issue of Hematology/Oncology Clinics, guest editors Drs. Kimmie Ng and Benjamin L. Schlechter bring their considerable expertise to the topic of Colorectal Cancer. Despite tremendous progress in the management of this disease, many questions and controversies remain regarding screening, adjuvant therapy for resected colon cancers, targeted therapies and immunotherapy for patients with advanced disease, surgical management, and more. In this issue, top experts in the field address provide clinicians with the tools to individualize management and optimize care for this growing patient population. Contains 13 relevant, practice-oriented topics including screening for colorectal cancer; hereditary colorectal cancer; disparities in colorectal cancer; microbiome in colorectal cancer; impact of diet and exercise on colorectal cancer; colorectal cancer in younger adults; and more. Provides in-depth clinical reviews on colorectal cancer, offering actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field. Authors synthesize and distill the latest research and practice guidelines to create clinically significant, topic-based reviews.

The hemodynamic significance of the flow properties of blood was put into perspective only during the past decade. Advances in modern technologies today allow the quantitative analy- sis of the fluidity of blood and its components under conditions approximating the flow in vivo, particularly those in the microcirculation. The hematocrit is the most important of the determinants of blood fluidity (reciprocal value of blood viscosity); acute increases in the hematocrit exert deleterious effects on circulation and oxygen transport owing to impaired fluidity of blood. High viscosity of plasma due to hyper- or dysproteinemias initiates the microcirculatory dysfunctions in hyperviscosity syndromes. Furthermore, the fluidity or deformability of red cells might be critically diminished and therefore cause redistribution of blood elements and adversely affect the resistance to flow within the microvessels. In low- flow states blood fluidity most likely becomes the key determinant for microvessel perfu- sion, overriding the neural and local metabolic control mechanisms operative at physiological conditions to adjust blood supply to tissue demand. Microcirculatory disturbances are there- fore encountered whenever driving pressures are reduced, as in shock or hypotension, and distal to stenoses of macrovessels, but also in hemoconcentration due to plasma volume con- traction, polycythemia, leukemia, and dysproteinemia. Based on experimental studies exploring the possibilities and limitations, with regard to improving the fluidity of blood by reducing the hematocrit, the concept of intentional hemo- dilution has been introduced to clinical medicine.

Levy, 10 Po: General Summary of the Meeting 507 Subject Index 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 515 1 Also special Lecture for the Wilsede Joint Meeting on Pediatric Oncolo- gy II 2 Were also presented in the Wilsede Joint Meeting on Pediatric Oncology II 3 Presented in the Wilsede Joint Meeting on Pediatric Oncology II xv Participants of the Meeting Anders, Fritz, Genetisches Institut der Universitaet, Heinrich-ButT-Ring 58-62,6300 Giessen, Federal Republic of Germany Bauer, Georg, Institut fuer Virologie im Zentrum fUr Hygiene, Hermann- Herder-Strasse 11,7800 Freiburg, Federal Republic of Germany Bell, Richard, Medical Oncology University Hospital, 75 East Newton Street, Boston, MA 02062, USA Bernhard, Silke, Dahlem-Konferenzen, Wallotstrasse 19, 1000 Berlin 33, Federal Republic of Germany Bister, Klaus, Max-Planck-Institut fUr Molekulare Genetik, Ihnestrasse 63-73, 1000 Berlin 33, Federal Republic of Germany Blattner, William A. , Family Studies Section, Environmental Epidemiology Branch, National Cancer Institute, Landow Building, Rm. 4C18, 7910 Woodmont Avenue, Bethesda, MD 20205, USA Boiron, Michel, Institut de Recherches sur les Leucemies et les Maladies du Sang, Universite Paris VII, Hopital Saint-Louis, 2 Place du Docteur-Four- nier, 75475 Paris Cedex 10, France Boniver, Jacques, Institut de Pathologie B 23, Laboratoire d'Anatomie, Pathologique, 4000 Liege, Belgium Bornkamm, Georg W. , Institut fuer Virologie im Zentrum fuer Hygiene, Hermann-Herder-Strasse 11,7800 Freiburg, Federal Republic of Germany Burgess, Antony W.