The provocative title stems from the recent International Blood Transfusion Symposium in Groningen, The Netherlands held under the auspicies of the World Health Organization (WHO), International Society of Blood Transfusion (ISBT) and Council of Europe (CoE). Transfusion medicine is a new discipline which has a wide remit. As defined recently, transfusion medicine deals with that part of the healthcare system which undertakes appropriate provision and use of human blood resources; transfusion practice is therefore a collective activity linking the blood donor with the patient. Transfusion medicine occupies areas in which it is deemed to be important or even essential that medical practitioners contribute to this bridging process. The broad issues and complex practices are presented in the masterly Introduction by the WHO's Assistant Director General with emphasis on education and multidisciplinary facets involving transfusion medicine. The challenging subjects are dealt in great details with a wealth of personal experience by 24 experts from the U.K., France, The Netherlands, U.S.A., Australia, Germany, Sweden, WHO and the Council of Europe. This is a comprehensive yet concise state of the art presentation involving donor and delivery system, ethics and legal elements, effects of modern techniques, importance of management and the future directions in this new economic environment. The book has been divided into four sections which discuss both the facts and the fiction.

Neuere Entwicklungen in der Molekulargenetik sowie die Notwendigkeit, unanfechtbare Beweise zu liefern, haben zu immer schnelleren Fortschritten auf dem Gebiet der H{mogenetik in der Gerichtsmedizin gef}hrt. Dieser Band enth{lt die Beitr{ge mit neuesten Erkenntnissen, die hierzu auf dem Kongre im September 1991 in Mainz vorgetragen wurden. Im Zentrum steht die Frage der forensischen Anwendung bzw. Andwendbarkeit der DNS-technologischen Forschung. Einige Artikel befassen sich mit Standardisierungs-, Artefakt- und Identifikationsproblemen bez}glich menschlicher ]berreste. Auch ethische und juristische Gesichtspunkte werden diskutiert.

Following the major breakthroughs in the and frequent and thorough exchange of treatment of acute leukemias in the seven- information. Hence, it was felt that a spe- ties by the introduction of intensive combi- cial series of symposia should be devoted to nation regimens, therapeutic progress has "Pharmacokinetics and Management of slowed down and the impression of stagna- Relapsed and Refractory Disease" comple- menting the established meetings on "Prog- tion may even have occured. In contrast, the knowledge about the biology of leu- nostic Factors and Treatment Strategies" kemias is rapidly expanding and allows new which will proceed in parallel. It was the insights into the pathophysiology of the aim of the international symposium disease. Further improvements also come "ACUTE LEUKEMIAS - Pharmacokine- from a better understanding of the pharma- tics and Management of Relapsed and cokinetics and pharmacodynamics of cyto- Refractory Disease" to provide an update static drugs and their mechanisms of action. of the present knowledge in this area and to Hence, novel treatment modalities can be stimulate further developments. As a sign developed on a more solid basis and ration- for the closing distance between countries al. These achievements need to be comple- and the development of effective world- mented by effective eradiation wide cooperation this symposium emerged of residual disease or its permanent control and new from the joint efforts of the German AML approaches have been derived from recent Cooperative Group and the M. D.

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.

With great pleasure I welcome you to the City of Groningen. In more than one way there is cause for celebration. Today marks the third lustrum of the annual international sympo sium on blood transfusion, organized by the Rode Kruis Bloedbank Groningen-Drenthe. In my opinion it has been a remarkable initiative of the Bloedbank, to start organizing a scientific conference, as it did, in 1976. It meant, among others, that in case of success the initiative would grow to be an annual item on the international congress calen der. It also meant that a possible third lustrum would coincide with the celebration of the 950th anniversary of the City of Groningen. I am happy to note that the initiative has been successful: over the past fourteen years the Rode Kruis Bloedbank Groningen-Drenthe has succeeded in organizing an annual symposium on blood transfusion, with a different theme each year, and with an average attendance of 250 participants from some 26 countries world-wide. The platform created with the special formula of the symposium, for science and industry, has been well balanced and beneficial to both. Mr. Chairman, ladies and gentlemen, I like to compliment the organizers with the success that they have attained. Allow me to men tion the name of just one person, in whom I like to thank everyone who has been involved in creating the annual Bloedbank-symposia: my warm congratulations to Dr. Smit Sibinga and his staff."

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well."

We are pleased to present our readers the proceedings of the International symposium on "New Aspects of Human Polymorpho- nuclear Leukocytes" which was held in Freiburg im Breisgau, FRG, from October 26-28th, 1989. The meeting provided an unique framework for close interaction between scientists from various disciplines, including bioche- mistry, biology, physiology, pathology, clinical chemistry, hematology, gynecology, surgery, intensive care medicine, nephrology, rheumatology, and infectious diseases. We would like to express our gratitude and appreciation for all those who have stimulated, encouraged, and supported us to hold the symposium in Freiburg. This endeavor could not have been possible without the generous financial support of Asid- Bonz (Boblingen), Bayer AG (Leverkusen), Bayropharm GmbH (Koln), Baxter (Munchen), Ciba-Geigy (Wehr/Baden), Cilag GmbH (Sulzbach), Fresenius AG (Oberursel), Gambro (Martinsried), Gry-Pharma GmbH (Kirchzarten), Hoechst AG (Frankfurt), Hospal (Nurnberg), Knoll AG (Ludwigshafen), Lederle-Cyanamid (Wolfratshausen) , E. Merck (Darmstadt), MSD Sharp and Dohme GmbH (Munchen), Pfizer GmbH (Karlsruhe), and Kabi/Pfrimmer (Erlangen). We are indebted to Mrs. I. Szkibik for her invaluable ass i- stance both with the organization of the meeting and the pre- paration of the manuscripts.

The first International Meeting on Apheresis was held in Dyon in 1984. At the congress it became clear that both the technical and therapeutic sides developed very rapidly and it appeared fruitful to bring together the investigators of the different countries working in the areas. At that time immunology had come to pervade many clinical specialities, and hemapheresis, especially plasmapheresis was considered a therapeutic tool in many immunological diseases which hitherto had proved to be fatal. New methods to identify certain antibodies and circulating immune complexes in the serum and the possibilities to remove them from the blood by several techniques (filtration, centrifugation, immunoabsorp tion) led to an almost uncontrolled use of plasma exchange in a variety of diseases. Since then the technical possibilities of this technique were further recognized, as was the impact of immunology on many diseases, and the possibilities to collect specific components for therapeutic pur poses. But also we became aware of the limited contributions of anec dotal data on successes or failures of apheresis as adjuvant treatment. Therefore international prospective studies were initiated to make critical assessment possible of apheresis in various diseases."

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte. The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy."

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."

The theme of this 14th International Symposium on Blood Transfusion is closely related to the work and scientific contributions of the Dutch cryobiology pioneer Dr. Herman W. Krijnen of the Dutch Red Cross Central Laboratory. Dr. Krijnen was known and respected in the national and interna tional blood transfusion community as an extremely competent scientist and a beloved and admired colleague. Dr. Krijnen was intentionally honoured with the invitation to open this symposium on cryopreservation and low temperature biology in blood transfusion and be the guest of honour at this event. Unfortunately, Dr. Krijnen suddenly died on the first of June 1989. In honour and mem ory of Dr. Krijnen this symposium will therefore be dedicated to him. Since the lOth International Symposium on Blood Transfusion in 1985 highlighted the theme of "Future developments in blood banking," major changes have occurred in the blood banking world. Most of these changes were forced upon the Blood Banks by the fear of spreading AIDS through contaminated donations. This not only led to the wide spread testing of blood, but also to a more appropriate counselling of the community and the blood donors in specific. Additionally, virus inacti vation techniques were introduced for those components derived from multiple donations and intended for a regular transfusion in haemophi lia patients and others."

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.

Proceedings of a Workshop sponsored by the Commission of the European Communities as advised by the Committee on Medical and Public Health Research and the Committee on Bioengineering Evaluation of Technology Transfer and Standardization

With this symposium the Red Cross Blood Bank Groningen-Drenthe affirms its well known reputation as an organizer of symposia of high standard and quality. Several important aspects of bloodbanking have been discussed in the past. The Blood Bank here is a specialist in its own field. Administrative processes in respect of the donor, information processes, the preparation of the blood and the laboratory process are automatized. New developments in these fields are undeway that you will certainly identify and investigate. I do hope that you will come to conclusions from which we can learn and get better results. As general manager of the Development and Investments Company for the Northern Netherlands - NOM - for several reasons I am very much interested in the outcome of this symposium. In the first place I am proud that the Red Cross Blood Bank Groningen Drenthe is doing its utmost to be excellent in regard of research, education and bloodprocessing. In being so, the Blood Bank can produce spinn-offs for healthservices and the related industry."

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.

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.

In 1628 William Harvey published his discovery of the existence of the microcirculation which he deduced from careful anatomical and physiological study. Thirty-three years later, Malpighi confirmed the presence of capillaries through direct microscopical observation. Subsequent scientific advance has been slow, and in view of the fact that microvascular in the genesis and expression of many pathophysiology may be implicated diseases, our know ledge of human microvascular function is surprisingly limited. This ignorance attests to the difficulty of studying something that is both minute and inaccessible without disturbing the quantity that is being measured. In the last fifteen years, however, direct techniques have been developed for studying human microvascular pressure, flow and permeability. These methods have provided new insights into human microvascular function in health and disease. At the same time there has been a steady growth of new indirect techniques based on a w ide range of physical principles that reflect some or other aspect of microvascular function.

Proceedings of the Tenth Annual Symposium on Blood Transfusion, Groningen 1985, organized by the Red Cross Blood Bank Groningen-Drenthe

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.