ABSTRACT

Introduction 872 Cytotoxic chemotherapy 872 History 872 Pharmacology of individual agents 872 Combination chemotherapy 878 Biologic therapy 878 Introduction 878 Interferon 878 Monoclonal antibodies 880 Radioimmunotherapy 883 High-dose chemotherapy with stem cell transplantation 884 History 884 High-dose chemotherapy 884

Methods of collection of hematopoietic stem cells 884 Source of stem cells 885 Efficacy 886 Miscellaneous therapies 887 Thalidomide and its analogues 887 Proteasome inhibitors (bortezomib) 888 Newer approaches 889 Vaccines 889 Newer monoclonal antibodies 889 Antisense therapy 889 Cytosine-phosphorothioate-guanine (CpG) oligonucleotides 889 Key points 889 References 889

Lymphoproliferative disorders are disseminated in nature and hence therapy for the lymphoid malignancies has shown an increasing shift away from local therapy and toward systemic therapy. For a long time, cytotoxic chemotherapy has been the mainstay of systemic therapy for the lymphoid malignancies, but increasing knowledge about the basic molecular biology of these illnesses has resulted in the increasing use of agents targeted against key metabolic pathways responsible for carcinogenesis. In this chapter we will discuss the basic principles of action of the various individual chemotherapeutic agents, the rationale of combining two or more individual agents together, the concepts of high-dose chemotherapy with stem cell support, the newer targeted agents including monoclonal antibodies and small molecules that affect key intracellular pathways, and finally look at agents that are currently being investigated.