This volume provides a comprehensive review of resistance induced by photodynamic therapy (PDT) in tumor cells. Understanding the underlying mechanisms in this process leads to the improvement of therapeutic modality, in combination with chemotherapy, immunotherapy, and radiotherapy. Photodynamic therapy is a minimally invasive therapeutic procedure that can exert a selective or preferential cytotoxic activity toward malignant cells. The procedure involves administration of an intrinsically non-toxic photosensitizing agent (PS) followed by irradiation at a wavelength corresponding to a visible absorption band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Studies reveal that PDT can be curative, particularly in early stage tumors and this volume explores the potential of PDT, but also reveals strategic approaches to overcome resistance in tumor cells.

Thesocietalburdenofcancerisoneofthemajorpublichealthchallengesofour time. Yetthatburdenisnotequallysharedbyall. Troublingdisparitieshave been documented not only by racial/ethnic group but also by social class, insurancestatus,geography,andahostofotherdimensions. Furthermore, suchdisparitiesrepresenttheendresultofaconstellationofforcesstemming frominsideandoutsidethehealthcaresystem. Manycancerdisparitiesshould bepreventable. Fewhaveattemptedtocapturethebreadthanddepthofthedimensionsof cancerdisparitiesfrombothclinicalaswellaspublichealthperspectives. To addressthisneed,wepresentthisvolumeto: broaden concepts of disparities beyond traditional discussions of race/ ethnicitytoexplorehow,where,andwhytheyoccur; focusoncancerdisparitiesintheUS,whilecitingsomemajorexamplesfrom abroad; analyzecertainmajorcancerswithrespecttodisparities,withemphasison socioeconomicposition; examinethesourcesofdisparitiesfrombothinsideandoutsidethehealth caresystem; identifyinitialinterventionsthatattempttoreduceandeliminatethesed- parities;and identifyissuesthatdeserveattentionwithrespecttofutureresearch. Ourmonographaddressescancerdisparitiesacrossthecontinuum(fromp- vention to mortality and by the domains of social inequality). We begin by exploringbroaddimensionsuchasdefinitionsofdisparities,datasystems,the roleofgenesandenvironment,andtheroleofworkandoccupationincancer disparities. Thenwemoveintospecificchallengesincancerdisparitiessuchas tobaccouseandlungcancer,breastcancer,colorectalcancer,prostatecancer, cervicalcancer,melanoma,andhepatocellularcarcinoma. Wethenconcludewith someavenuestoaddresscancerdisparities,includingpolicyandadvocacy,health v vi Preface communication, overcoming barriers to cancer care, and community-based approaches. Oureffortsarefarfromexhaustive,buttheyrepresentoneofthe firstattemptstoaddresscancerdisparitiesfromsuchacomprehensiveperspective. Thisvolumereflectstheworkofanumberofnationalexpertsincancer disparities. Many are members of the Executive Committee of the Cancer Disparities Program-in-Development of the Dana-Farber/Harvard Cancer Center. Still others are also investigators in the National Cancer Institute Community Network Program MassCONECT (Massachusetts Community NetworkstoEliminateCancerDisparitiesthroughEducation,Researchand Training). Also,thisvolumeupdatesandexpandsaearlier2005monographon thetopicpublishedinthejournalCancerCausesandControl. Allauthorsare dedicatedtothegoalofeliminatingcancerdisparitiesandIamindebtedto them. IamparticularlygratefultoRachelWarren,TerraZipoyrnSnider,andDr. ClaudiaArriggfortheirunendingencouragementandsupport. Itismyhope thatthismonographrepresentsanothercontributiontowardhelpingallpeople enjoytheirhighestattainablestandardofhealth. Boston,MA HowardK. Koh,MD,MPH Contents PartI DimensionsofCancerDisparities 1 Defining,Investigating,andAddressingCancerInequities: CriticalIssues...3 NancyKrieger,KarenM. Emmons,andDavidWilliams 2 CancerDisparities:DataSystems,Sources,andInterpretation...29 BarbaraD. Powe,AhmedinJemal,DexterCooper, andLokieHarmond 3 Genes,Environment,andCancerDisparities...49 AlexandraE. Shields,StephanieM. Fullerton,andKennethOlden 4 WorkandOccupation:ImportantIndicatorsofSocioeconomic PositionandLifeExperiencesInfluencingCancerDisparities...83 GlorianSorensen,GraceSembajwe,AmyHarley, andLisaQuintiliani PartII SpecificChallengesinCancerDisparities 5 DisparitiesinTobaccoUseandLungCancer...109 HowardK. Koh,LorisElqura,andSarahMassinShort 6 SocioeconomicStatusandBreastCancerDisparities...137 SherrieFlyntWallington,OtisW. Brawley, andMichelleD. Holmes 7 DisparitiesandColorectalCancer...161 EricC. Schneider 8 DisparitiesinProstateCancer...179 OtisW. BrawleyandSherrieFlyntWallington vii viii Contents 9 DisparitiesandCervicalCancer...203 MarceladelCarmenandTeresaDiaz-Montez 10 MelanomaandPrimaryHepatocellularCarcinoma...227 ChristopherA. Aoki,AlanGeller,andMoonS. Chen PartIII SomeAvenuestoAddressCancerDisparities 11 Interventions,Policy,andAdvocacy...259 DeborahKleinWalkerandChristineM. Judge 12 HealthCommunicationandCommunicationInequalities inAddressingCancerDisparities...277 K. ViswanathandKarenM. Emmons 13 OvercomingBarrierstoCancerCare:PatientandPublic Perspectives...299 KarenDonelan 14 Community-BasedApproachestoCancerDisparities...317 BarbaraGottlieb Index...359 Contributors ChristopherA. Aoki DivisionofGastroenterologyandHepatology, DepartmentofInternalMedicine,SchoolofMedicine,Universityof California,Davis,CA OtisW. Brawley AmericanCancerSocietyandEmoryUniversity,Atlanta,GA MarceladelCarmen DivisionofGynecologicOncology,Massachusetts GeneralHospital,HarvardMedicalSchool,Boston,MA MoonS.

This volume brings together the key research issues in clinical and laboratory science relating to metastasis in prostate cancer. It is especially suitable for those in the field, whether physicians and/or scientists, and whether in active research or in training, who wish to broaden their understanding, with regard to their own discipline, and also to another. It is also a resource for those whose research is in metastasis, but in diseases other than prostate cancer. The intention of this volume is to help to empower those who seek to further exploit the potential for translational research in this field.Written by a team of internationally recognised experts, coverage ranges from the most fundamental aspects of the molecular biology of metastasis, to the patient in the clinic. The therapeutic approaches range from conventional drug design to immunogene therapy.

This new work on oral complications of cancer chemotherapy is edited by two dentists who have made pioneering contributions in this previously neglected area. Their efforts have established the invaluable role of the dentist in oncologic research and cancer patient management. The editors have collected nine chapters that will be of interest to dentists and dental hygienists, oncology nurses, and all physicians treating cancer patients with chemo therapeutic agents. Background chapters on oral complications of cancer chemotherapy, the pharmacology of chemotherapeutic agents, and principles of infection management and prevention set the stage for more specific chapters focusing on prevention and treatment of chemotherapy induced oral and dental disorders. Valuable contributions to the supportive care of the cancer patient are contained in this book. A full comprehension of this book, coupled with an appreciation for advances in other areas of supportive care, such as antiemetic therapy and pain control, will allow all those involved in cancer treatment to be more successful. Peter H. Wiernik, M.D. Emil Frei, M.D."

The hybridoma technique for producing monoclonal antibodies developed by Drs. Kohler and Millstein in 1975 revolutionized the field of tumor immunology. It is now clear that there are antigens associated with or restricted to human neoplasms that have biologic significance. Monoclonal antibodies have already been demonstrated to have great immunodiagnostic value, and it is anticipated that they will become a component of our therapeutic armamentarium. Most investigators in the field, however, feel the true potential of monoclonal antibodies in cancer therapy remains to be determined. Clearly the most encouraging results have been witnessed in the treatment of hematologic malignancies. This volume of Cancer Treatment and Research explores the current state of the art of immunoconjugate therapy of hematologic malignancies. The first chapter, authored by Drs. Rosen and Kuzel, reviews the current status of radioimmunotherapy of lymphoma. Results of clinical investigations utilizing radiolabeled immunoconjugates in B-cell lymphomas, T-cell lym- phomas, and Hodgkin's disease are discussed. In addition, obstacles to effective antibody therapy are highlighted and toxicities are summarized. Chapter 2, written by Drs. Sgouros and Scheinberg, critiques the treat- ment of leukemia with radiolabeled monoclonal antibodies. In this chapter, the unique features of leukemia that make it particularly suitable for radio- immunotherapy are discussed, an overview of selected clinical trials is presented, and a treatment planning approach to radioimmunotherapy in- corporating biologic and physical parameters is reviewed.

Volume 12 in this series explores the latest experimental and clinical uses of stem cells in the treatment of disease and of injuries and reviews methods for isolating multipotent endothelial-like cells from human adipose tissue and discusses clinical applications in cell therapy and regenerative medicine.

The book is organized in five parts: Cancer Stem Cells, Pluripotent Stem Cells, Dendritic Stem Cells, Regenerative Medicine and General Applications. The first section includes chapters on histamine in the neural and cancer stem cell niches and emerging concepts of stem cell organization in the normal lung and in lung cancer. The section on Pluripotent Stem Cells includes discussion of the differentiation of dendritic cells from human induced pluripotent stem cell and the molecular mechanisms involved in reprogramming human somatic cells to generate induced pluripotent stem cells. Additional chapters cover the differentiation of induced pluripotent stem cells into functional cardiomyocytes, characteristics of satellite cells and multipotent adult stem cells in the skeletal muscle. The section on Dendritic Stem Cells explores the critical role of notch signaling in the differentiation and function of dendrite. Other chapters cover hypertensive emergencies in children after stem cell transplantation and overcoming the radio resistance of lung cancer stem cells. The section on Regenerative Medicine reports on experiments on improved renal revascularization in pigs using stem cells and phenotypic correction of murine Hemophilia A using cell-based therapy. The concluding section, General Applications, discusses such topics as methods in mathematical modeling for stem cells, as well as molecular and functional characterization of human adipocytes.

Like its eleven predecessors in the series," " this volume stands out for its comprehensive approach, its roster of some 51 expert contributors representing a dozen different countries and its up-to-date review of leading-edge technology and methods.

A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (Velcade (TM)) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, genitour inary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

Transferring hematopoietic stem cells and immune cells has continued to be a promising therapeutic alternative and a fascinating area of cell biology as well as a field of persistent procedural problems. This explains why substantial parts of basic research on cell growth and differentiation, immune tolerance and antitumor effects, gene transfer, minimal residual disease and supportive care have settled around clinical transplantation in hematology and oncology. This second volume updates the current role of allogeneic and autologous transplantation in leukemias, lymphomas and solid cancers, including controversial strategies and novel experimental approaches. Outstanding representatives of leading groups guarantee first-hand information and indicate how we can work and cooperate more effectively to the benefit of our patients.

A comprehensive state-of-the-art summary of breast cancer research and treatment by leading authorities. The book's many distinguished contributors illuminate the biology and genetics of breast cancer, including what is known about the hereditary breast cancer genes, BRCA1 and 2, the cutting-edge cytogenic approaches, and the biology of breast cancer metastasis. In addition, the authors describe current and future methods of breast cancer treatment in depth, and discuss environment and diet as risk factors for the disease. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics constitutes an excellent reference and resource for all those clinical and experimental oncologists, as well as genetic counselors nurses, who need to understand the latest developments in breast cancer biology, risk, and treatment.

The field of genito-urinary oncology is rapidly evolving at virtually every level. Significant advances have been made in our understanding of the molecular and cellular events which contribute to the generation of GU malignancies. At the same time, similar advances have been made in the clinical arena which have improved the diagnosis and treatment of urologic cancers. This volume attempts to summarize those advances which most impact us as clinicians, and has been divided into three sections. Section One, `Diagnostic advances: the use of molecular medicine in the diagnosis and prognosis of GU malignancies', details how epidemiologic studies and new molecular techniques are impacting our ability to diagnose and treat GU tumors. Section Two, `Surgical and radiation advances', details the recent major advances in the treatment of organ-confined cancers. Section Three, `Medical advances', addresses major issues in the treatment of metastatic disease. This volume will serve as a compendium of the advances, both at the basic science and clinical levels, which are currently impacting practicing oncologists and urologists.

This book provides an up-to-date comprehensive overview of the exciting new developments shaping the current and future practice of radiation oncology. Advances in treatment planning and delivery, in biological targeted therapies combined with radiation and in functional and molecular imaging are all covered in a single volume. All of these advances are discussed by leading experts in the field and with a critical evaluation of their clinical relevance throughout.

In recent decades eicosanoids have been attracting an increasing amount of attention as a result of their important physiological roles in many areas of biology and medicine. The eicosanoids comprise the prostaglandins, thromboxanes and leukotrienes and are products of arachidonic acid, an essential polyunsaturated fatty acid stored in tissue phospholipids. Disturbances of eicosanoids and their metabolic products play a regulatory role in many types of cell injuries and diseases. One of the most exciting areas of eicosanoid research pinpoints their participation in the control of cell proliferation and differentiation. Eicosanoids form a link between different fields of research into such areas as cancer, inflammation and radiation-induced injury. This link provided the impetus for the development of the conference series of which the present volume represents the proceedings of the Second International Conference, held in Berlin in October 1991.

The title of this monograph, Brain Tumor Research and Therapy, is the name of the Conference itself, which had its inaugural meeting in the United States in 1975 andhas since progressed to the international scale. In Japan, the first conference ofits kind was organized by Dr. Takao Hoshino and me and was held at Nikko in 1980, hence its name, the Nikko Conference on Brain Tumor Research and Therapy. Though it started as a small, closed meeting, the conference has grown considerably, and in 1992 it was reorganized as the Japanese Conference on Brain Tumor Research and Therapy and was opened to all neurosurgeons and neuropathologists interested in the study of brain tumor problems and who are participating in this field. The main purpose of the Conference on Brain Tumor Research and Therapy is the candid and informed discussion of the most up-to-date developments in basic re search and clinical treatment of brain tumors. The 3rd Japanese Conference on Brain Tumor Research and Therapy was held at Nasu (Tochigi Prefecture), Japan, in No vember 1994. It was a great honor to welcome many distinguished guests from over seas who kindly attended each session and made valuable contributions.

This book provides a comprehensive, highly readable overview of our current knowledge of the molecular pathology of basal cell and squamous cell carcinomas. The chapters present the newest findings in epidemiology, photocarcinogenesis, genetics, immunology and molecular pathology of these epithelial skin tumours. Topics include the importance of the hedgehog/patched/smoothened/GLI, p53, PDGF, or TGF-b signalling pathways as well as the relevance of papilloma virus infections, apoptosis, DNA-repair and telomerase.

There have been significant advances in the treatment of sarcomas in the past several years. Further, different clini cal treatment programs are being advocated in different areas including surgery alone, surgery with preoperative or post operative chemotherapy, surgery with different radiotherapy modalities, with each investigator espousing his own treat ment program. On the other side, there is the question of whether these treatment programs are offering better results or whether the natural history of sarcomas has changed. The International Symposium on Sarcomas was held at Innisbrook Resort, Tarpon Springs, Florida, October 8-10, 1987. This was the first international symposium to date involving all of the disciplines treating sarcomas including pathologists, orthopaedic surgeons, general surgeons, medical oncologists, pediatric oncologists, and radiation oncol ogists. The Symposium brought together a number of special ists working in the clinical field of sarcomas for a presen tation of their specific treatment programs and their results. The presentations were followed by panel discussions to stimulate educational debate as to the different forms of treatment for sarcomas and to formulate some conformity in control of disease, control of spread, and ultimate function for the patient. James R. Ryan, M.D."

Over one hundred contributions detail advances in the molecular and cellular biology of eicosanoid production, as well as their role in signal transduction. One of the most exciting developments explored within this collection of articles is the expression of the novel isoform of cyclooxygenase (cox-2), which may play a large role in the development of anti-inflammatory drugs.

As in CANCER CHEMOTHERAPY 1, this volume brings to the reader highlights in three different areas of cancer therapeutics: new concepts and models; drug classes; and clinical settings. Topics were chosen because of their timeliness or probable current impact in cancer treatment. Authors were selected on the basis of their ability to provide a critical overview of specific subjects and their involvement in original work. I shall review the aims of this second volume, and then elaborate on the scope of its con tents. The principal aim of the volumes on cancer chemotherapy in the' Cancer Treatment and Research' series, as stated in the preface to the first volume, is to assemble in a concentrated form selected ingredients of chemothera peutic progress. These ingredients are to include concepts in therapeutic strategy, pre-clinical studies, development of major classes of compounds, identificatlon of new directions and of landmarks of clinical progress. Thus we do not foresee overlap with series which provide an yearly update of chemotherapy in an encyclopedic manner, or reviews of cancer chemother apy. Unlike those publications, our volumes are not intended to seek a place in shelves as a reference manual. It is this Editor's hope that persons repre senting various biomedical disciplines will seek the' Cancer Treatment and Research' chemotherapy volumes to survey advances in the field at regular intervals.

NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.

A long time has passed since the war act on Cancer declared by former USA president Nixon, almost half a century ago. Today, after so many years of feverish research and uncountable efforts worldwide, the end of the war appears far as ever, whereas the fight is leading researchers to newer and newer battlefronts while frontiers in bioscience are continuously being surpassed. In this scenario, "The Selfish Cell" is a script record of the most important strategic points gathered during these years of war, with the goal to provide solid ground onto which to step ahead for future assaults against this terrible disease. At the same time, it is an attempt to shift the debate on cancer toward a more peaceful and possibly productive semantic terrain, where to reflect with the aid of superior wisdom to finally get out of that terrible chaos of fight and death dominating our days. In this perspective, "The selfish cell" becomes an occasion for reflecting the limits of our human selfishness and their consequences on both our social and natural environment.

This volume provides insight into recent developments on experimental and clinical strategies for cancer gene therapy. Gene Therapy of Solid Cancers: Methods and Protocols guides readers through protocols on gene therapeutic strategies in combination with helpful technical notes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Gene Therapy of Solid Cancers: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Breast cancer is not only a burning public issue, but very soon we shall see genetic testing for a woman's predisposition to breast cancer. Many women will be demanding to know their degree of risk and will need counselling to cope with that information. This book is particularly aimed at primary health care professionals, including physicians, medical assistants, nurses and counsellors, who daily deal with questions from women concerned about their risk of developing breast cancer. To answer such questions, this book has combined a guide to identifying women at higher risk to breast cancer, with a balanced review of approaches which aim to reduce that risk. The book provides practical general measures which may reduce risk for women at average risk. For women at clearly increased risk various protective options with different levels of efficacy and acceptability are discussed. Central to the book is the patient-centered view. We need to face reality that it still will take many years before the current clinical trials of preventive measures provide meaningful results. Meanwhile, women who seek to diminish their risk of breast cancer need all the available information. They must be given full responsibility to make an informed decision on their own health care. Reducing Breast Cancer Risk in Women is a practical handbook, technicalities have been deliberately kept to a minimum, making it concise and easy to read.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfor tunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung can cer, genitourinary cancer, pediatric oncology, etc. Second, by asking emi nent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

Blood Stem Cell Transplantation conveys the excitement that accompanies the newest developments in hematopoietic stem cell transplantation. Some of the applications that stand to impact this field most significantly are based on recent advances in the biological sciences, as demonstrated by the chapters on gene therapy, on the detection of minimal residual disease using molecular techniques, and on the use of radioimmunoconjugates targeting lymphoma and leukemia-associated antigens. Others are the results of clinical observations - e.g., the association between graft-versus-host- disease (GVHD) and durable remissions that have led to creative clinical experiments such as donor leukocyte infusions (DLI). Attempts to unravel the biological events that underlie the responses seen in patients with relapsed chronic myelogenous leukemia treated with DLI are likely to provide the basis for future refinements in this clinical approach. Hopefully, improved response rates and reduced toxicity will result. The power of the immunologic response in controlling malignant disease is underscored in the chapter on post-transplant immunotherapy. The complex immunologic process that results in clinical GVHD may be dissected and engineered to provide clinical benefits that include, in addition to its antineoplastic effects, the amelioration of its clinical manifestations. Better control of GVHD with less global immunosuppression will facilitate the use of mismatched and unrelated donors. This area of investigation perfectly illustrates the continued interplay between the laboratory and the clinic. The continued cross-fertilization of ideas between immunologists, molecular biologists and clinical investigators is likely to yield important advances in this field for years to come. Possible applications of stem cell transplantation continue to grow with the identification of alternative sources of stem cells and the potential to engineer and/or expand the graft. Although the use of unrelated and mismatched donors continues to increase, the possibilities associated with umbilical cord blood transplantation are legion, especially if stem cells can be expanded ex vivo to provide grafts for full-sized adults. Using techniques in which contaminating malignant cells may be eliminated from autografts through positive selection, autologous transplantation may prove highly effective, especially when coupled with post-transplant immunotherapy. Some of these same methodologies have helped facilitate the use of autologous grafts for transplantation in patients with chronic myelogenous leukemia without allogeneic donors. Advances in the supportive care of transplant patients, including the pretransplant identification of those at risk from pulmonary complications and the use of cytokines to speed engraftment, have reduced morbidity and mortality to such a degree that it is appropriate to consider high-dose therapy and stem cell reconstitution in patients with nonmalignant diseases. The impressive advances that have occurred in transplantation for thalassemia are described by pioneers in their area of investigation. The burgeoning field of transplantation for autoimmune disorders, including its immunobiologic basis and soon-to- be-realized clinical potential, is also summarized. Continued progress in the use of high-dose therapy with stem cell rescue for the treatment of pediatric tumors, which derives in part from improved supportive care, is detailed. The sobering voice of the health care economists underscores the necessary limitations to our seemingly unbridled imagination. Cost- consciousness and financial know-how will need to be reflected in future study designs. Given the seemingly endless applications of our technology, strategies to insure its cost-effectiveness will be necessary. Continued financial support for laboratory investigation and for the clinical experiments they generate will be required if we are to go forward. Blood Stem Cell Transplantation lays the foundation for many of these future advances; it is incumbent upon us all to insure its realization.