Emerging concepts in the management of the malignant haematological disorders.
A comprehensive review of novel cytoreductive agents is presented. Such novel agents may be found among chemical compounds directed against specific molecular targets (cytostatics) or within the biological substances selectively aimed at the malignant clone (immunotherapy). It is stated that the purposes of immunotherapy in general are to generate a T-lymphocytic response against the tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system of the tumour-bearing host by DNA and/or RNA manipulation with subsequent interference with the signalling pathway in the tumour cells. Some immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene replacement therapy, suicide gene therapy, antisense oligonucleotides, alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most likely, a sequence of different treatment modalities will be used in the future comprising an initial debulking by means of standard chemotherapy and/or irradiation followed by target unspecific immunotherapy (polyclonal immunoglobulins, GvL effect etc.) and finally target specific elimination of residual tumour, probably with repeated use of the minimum effective pharmacologic dose (MEPD) of the agents used. In contrast, the current use of high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD) and associated severe organ toxicity, and high rates of secondary malignancies will probably be substituted in the future. An effective supportive treatment will be highly necessary, especially related to prevention and treatment of infections.
Haematology Department L 4042, Rigshospital, Copenhagen, Denmark.
V
V
Jønsson
C G
CG
Gemmell
A
A
Wiik
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000191:economics / Q000209:etiology / Q000601:surgery / Q000628:therapy*; D006801:Humans; D010166:Palliative Care
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents