Lonial Myeloma Therapy

Pursuing the Plasma Cell
2008
ISBN: 978-1-59745-564-0
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 670 Seiten, eBook

Reihe: Contemporary Hematology

Therapeutic options for patients with myeloma have dramatically changed over the past 10 years. Beginning with the advances in therapy resulting from the use of high-dose therapy and autologous bone marrow or stem cell tra- plant, we have more than doubled the median survival for patients as a whole, and have now have a wealth of different biology -based treatment approaches for our patients in all disease stages. This book represents state-of-the-art information from many of the leaders in the plasma cell disorders world. Sections focusing on disease pathogenesis and biology, chemotherapy-based approaches, immune -based therapies, currently approved novel agents, developing targets, supportive care, and other plasma cell disorders provides a comprehensive collection and an excellent resource in this time of rapid change in clinical and preclinical disease knowledge. It is important to realize that these changes did not occur in a vacuum. Partnerships between academic institutions, the pharmaceutical industry, patient advocacy groups, the National Cancer Institute, community onco- gists, and ultimately our patients worked closely together to realize these advances, and to effect the radical changes in therapy we have witnessed over the past few years. This book would not have been possible without contri- tions from each of the gifted scientists and clinicians who worked tirelessly to prepare their individual chapters all the while maintaining commitment to the scientific and clinical mission of advancing care.

Zielgruppe

Professional/practitioner

Autoren/Hrsg.

Lonial, Sagar

Inhaltsverzeichnis

Biologic Consideration and Myeloma.- Staging in Multiple Myeloma.- Epidemiology of Multiple Myeloma.- Basic Biology of Plasma Cell Dyscrasias: Focus on the Role of the Tumor Microenviroment.- Biology-Based Classification and Staging of Multiple Myeloma.- Cytogenetic Abnormalities in Multiple Myeloma: The Importance of FISH and Cytogenetics.- Historical and Cytotoxic Agent-Based Therapies for Myeloma.- Role of Autologous Stem Cell Transplantation in Multiple Myeloma.- Maintenance Therapy in Multiple Myeloma.- Therapy for Patients not Eligible for Autologous Transplant.- Current Role of Anthracyclines in the Treatment of Multiple Myeloma.- Immune-Based Therapies.- Allogeneic Transplantation for Multiple Myeloma.- Immunobiology and Immunotherapy of Multiple Myeloma.- Antibody and Other Immune-Based Therapies for Myeloma.- Existing Novel Agents.- Thalidomide in Patients with Relapsed Multiple Myeloma.- Thalidomide: Induction Therapy.- The Role of Bortezomib in the Treatment of Relapsed and Refractory Multiple Myeloma.- Bortezomib as Induction Therapy in Patients with Multiple Myeloma.- Lenalidomide in Relapsed or Refractory Multiple Myeloma.- Lenalidomide for Initial Therapy of Newly Diagnosed Multiple Myeloma.- Current and Future Targets.- The Role of Heat Shock Protein 90 as a Therapeutic Target for Multiple Myeloma.- The PI3 Kinase/Akt Pathway as a Therapeutic Target in Multiple Myeloma.- The Mammalian Target of Rapamycin and Multiple Myeloma.- CDK Inhibitors in Multiple Myeloma.- Fibroblast Growth Factor Receptor 3 and Multiple Myeloma.- Histone Deacetylase Inhibitors in Multiple Myeloma.- Death Receptors in Multiple Myeloma and Therapeutic Opportunities.- Proteasome Inhibitors as Therapy in Multiple Myeloma.- Supportive Care.- Pathophysiology of Bone Disease in Multiple Myeloma.- Anemia and Erythropoeitic Growth Factors in Multiple Myeloma.- Percutaneous Vertebroplasty and Balloon Kyphoplasty for the Treatment of Acute Painful Pathologic and Nonpathologic Fractures.- The Role of Anatomic and Functional Imaging in Myeloma.- Management of Multiple Myeloma Patients with Renal Dysfunction.- Other Plasma Cell Disorders.- Waldenstrom's Macroglobulinemia.- AL (Immunoglobulin Light-Chain) Amyloidosis.- POEMS Syndrome and Other Atypical Plasma Cell Disorders.- Monoclonal Gammopathy of Undetermined Significance.

Leseproben

Chapter 3 Basic Biology of Plasma Cell Dyscrasias: Focus on the Role of the Tumor Microenviroment (S. 23-24)

Marc S. Raab and Kenneth C. Anderson

Introduction

B-cell development involves several mechanisms of remodeling Ig genes: VDJ recombination, somatic hypermutation, and Ig heavy chain (IgH) switch recombination. Once matured, B-cells reside in secondary lymphoid tissues. Antigen interaction induces proliferation and differentiation to lymphoblasts, leading to the generation of short-lived pregerminal center plasma cells. An antigen-activated lymphoblast entering a germinal center undergoes a unique modification of Ig genes through sequential rounds of somatic hypermutation and antigen selection, as well as by IgH switch recombination. Postgerminal center B-cells may become plasmablasts that have successfully completed somatic hypermutation and IgH switching before migrating to the bone marrow (BM), where stromal cells enable terminal differentiation into nonproliferating long-lived plasma cells. 1 , 2

Multiple myeloma (MM) is a malignant disease of terminally differentiated B-cells that may be preceded by a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). This is present in 1% of adults over the age of 25 years, the prevalence increasing with age. MGUS cells, like MM cells, secrete a monoclonal immunoglobulin and progress to malignant MM at a rate of 1% per year. Compared to MM, MGUS is characterized by a lower tumor burden (intramedullary tumor cell content less than 10%) and the absence of osteolytic lesions. Another disease related to aberrant plasma cells is amyloidosis, which shares most of the pathologic features of MGUS except that the secreted monoclonal immunoglobulin forms pathological deposits in various tissues.

Myeloma Genetics: A Brief Overview

Both MGUS and MM are characterized by the accumulation of transformed plasma cells at multiple sites in the BM. These cells show a marked karyotypic complexity with gains and losses of whole chromosomes, nonrandom chromosomal translocations causing dysregulation of genes at the breakpoints, and point mutations of genes, all contributing to disease pathogenesis. 6 , 7 In addition, small focal lesions of the MM genome as well as epigenetic changes have recently been identified 8 – 11 Briefly, MM patients can be subdivided into two groups based on the pattern of chromosomal gains and losses.

12 Approximately 55% of patients have a hyperdiploid karyotype (number of chromosomes 48–74) with trisomies of odd-numbered chromosomes including 3, 5, 7, 9, 11, 15, 19, and 21. The remaining cases (summarized as the nonhyperdiploid group) consist of patients with hypodiploid, near-diploid, pseudodiploid, or near-tetraploid chromosome numbers with less than 48 or more than 74 chromosomes.