Chapter 1. Blood Cell Malignancies: Disease Characteristics and Epidemiology
1.1. Leukemias
Acute Lymphocytic Leukemia
Chronic Lymphocytic Leukemia and Related Diseases
Acute Myeloid Leukemia
Chronic Myeloid Leukemia and Myelodysplastic Syndromes
1.2. Lymphomas
Hodgkin’s Disease
The Broad Spectrum of Non–Hodgkin’s Lymphoma
1.3. Myeloma and Plasmacytoma
Chapter 2. Oncogenes, Translocations, and Surface Antigens: Keys to Diagnosis
and Rational Therapy
2.1. Chromosomal Alterations as Defining Signs
2.2. Computer-Assisted Cytogenetic Diagnostics: Invaluable Aids for Therapy
Selection
2.3. Lymphocyte Surface Antigens as Diagnostic Markers and Therapy Targets
2.4. A Limited Role for
In Vivo Imaging
2.5. Molecular Biology for Diagnosis and Monitoring of Hematological Malignancies
Chapter 3. Current Therapies and Unmet Need
3.1. Small Molecules
Steroids
Alkylating Agents
Mitotic Spindle Modulators
Antimetabolites
DNA Hypomethylating Agents and Histone Deacetylase Inhibitors
3.2. Proteins and Antibodies
Enzymes
Monoclonal Antibodies
3.3. Acute Lymphocytic Leukemia
3.4. Chronic Lymphocytic Leukemia
3.5. Acute Myeloid Leukemia and Acute Promyelocytic Leukemia
3.6. Myelodysplastic Syndromes
3.7. Chronic Myeloid Leukemia
3.8. Hodgkin’s Disease
3.9. Non–Hodgkin’s Lymphoma
Rituxan
The Bexxar Regimen
Zevalin
3.10. Myeloma and Plasmacytoma
Chapter 4. Newly-Approved Drugs and Candidates in Development
4.1. New Formulations
Marqibo: A Liposomal Vincristine
A New Formulation of Aminopterin
Ceplene plus Interleukin-2
4.2. Nucleotide Analog Antimetabolites
Clofarabine
Next in Line: Dacogen
Arranon (Nelarabine)
4.3. New Alkylating Agents
Cloretazine
Treanda (Bendamustine)
4.4. Protein Kinase Inhibitors
BMS-354825 and AMN-107: Overcoming Gleevec Resistance?
Sorafenib
Lestaurtinib
Tandutinib
VX-680
4.5. Topoisomerase Inhibitors
Pixantrone
Banoxantrone
Annamycin
Elsamitrucin: A Natural Compound
4.6. Histone Deacetylase Inhibitors
PXD-101
Merck’s SAHA (Suberanilohydroxamic Acid)
4.7. New Mechanisms, New Uses
Fodosine: A New Hope for T-Cell Malignancies
Farnesyltransferase Inhibitors
-Zarnestra
-Sarasar
ABT-510
Telik’s Telintra
An Emerging Strategy: Heat Shock Protein Inhibitors
Noscapine
Aplidine
Potential Use Extensions for Proleukin
Two Broader Uses for Trisenox
Velcade in Mantle Cell Lymphoma
SDX-101: A New Application for an Old Nonsteroidal Anti-Inflammatory Drug
Pharmacyclics’ Xcytrin: Second Uses in Blood Malignancies
4.8. Small-Molecule Immune Modulators
Celgene Corporation’s Revlimid: A Thalidomide Analog for Myelodysplastic
Syndromes
Ziopharm’s Follow-Up Candidates on Trisenox
Talabostat
4.9. Antisense Drugs
Genasense
MG-98
LR3001: A New c-myb Antisense Drug
GTI-2040
SPC-2996
4.10. Vaccines, Cell Therapies, and Protein Immunostimulators
Stimulated Autologous T Cells
Gene Therapy with Transduced Autologous Cells
GVAX: An Adoptive Immunotherapy
An Anti-Idiotype Vaccine for Non–Hodgkin’s Lymphoma
PR1 Antigen Elicits Cellular Immune Response against Myeloid Leukemia Cells
LymphoRad: A Radiolabeled B-Cell Stimulator
4.11. Monoclonal Antibodies
The HuMax Series
Lintuzumab
AVE-9633
An Antibody-Targeted Immunotoxin
Chapter 5. Structure of the Hematological Cancer Market and Its Perspectives
Chapter 6. Company Profiles
6.1. Actinium Pharmaceuticals, Inc.
6.2. BioCryst Pharmaceuticals, Inc.
6.3. Celgene Corporation
6.4. Cell Genesys, Inc.
6.5. Cell Therapeutics, Inc.
6.6. Genencor International, Inc.
6.7. Inex Pharmaceuticals Corporation
6.8. Lorus Therapeutics, Inc.
6.9. Pharmion Corporation
6.10. Vion Pharmaceuticals, Inc.
References
Glossary
Index
List of Figures
Figure 1.1. B-Cell Cancers by Cell Development
Figure 1.2. Cancer Deaths by Gender, United States, 2004
Figure 1.3. The “Philadelphia Chromosome” Translocation
Figure 3.1. Prevention of Methylation-Induced Gene Silencing through Inhibition of DNA Methyltransferase Using Nucleoside Analogs
Figure 3.2. DNA Methyltransferase and Histone Deacetylase Enzymes Synergize to Prevent Access of Transcription Factors to DNA by Condensing Chromatin
Figure 4.1. The Chemical Structure of Thalidomide and Lenalidomide
Figure 4.2. Potential Antigen Targets for Immunotherapy in Leukemia
Figure 4.3. Activation and Proliferation of Patient T Cells by Autologous Chronic Lymphocytic Leukemia Cells before (Pre Rx) and 6 Months after (Post Rx) Infusion of Ad-CD154–Transduced CLL Cells
List of Tables
Table 1.1. Incidence and Annual Deaths from Main Types of Leukemias, United States, 2004
Table 3.1. FDA-Approved Monoclonal Antibody Drugs for Leukemia and Lymphomas
Table 3.2. Rituxan Adoption Rates in Non–Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia
Table 5.1. Drug Candidates with Submitted New Drug Applications or in Confirmed Active Phase III for Hematological Cancers
Table 5.2. New Chemical Entities in Top Clinical Stages I/II or II for Hematological Cancers
Table 5.3. Monoclonal Antibodies, Antisense Oligonucleotides, Cell Therapies, and Immunotoxins in Top Clinical Stages I, I/II, or II for Hematological Cancers
