Over the past decade, better understanding of the biology and pathogenesis of various neoplastic disorders, as well as improved supportive care measures and better understanding of the mechanisms of action of therapeutic agents, have led to significant advances in the treatment of a number of malignancies. This has been particularly true for lymphoproliferative disorders where better diagnostic techniques have allowed improved classification and definition of distinct biological subtypes. This has led to identification of tumour-specific targets and as a result, agents with the ability to discriminate between normal and neoplastic cells have been developed.
Monoclonal antibodies targeting specific tumour-related surface antigens have been under investigation in the treatment of both haematological malignancies and solid tumours. However, antibody-based immune therapy has been particularly successful in treating lymphoid neoplasms and a number of these agents have been effective in achieving responses in a variety of B- and T-cell disorders. One of these new antibodies, alemtuzumab, is a humanised monoclonal antibody against CD52, a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is highly expressed on normal T and B lymphocytes and on a large proportion of malignant lymphoid cells, but not on haematopoietic progenitor cells. Alemtuzumab has demonstrated significant activity against a number of T-cell malignancies that have traditionally been difficult to treat.
Mature T-cell leukaemias are relatively uncommon neoplasms that are derived from mature or post-thymic T cells . Their tissue counterparts are T-cell lymphomas. These and other T-cell disorders such as peripheral and cutaneous T-cell lymphomas account for a relatively small percentage of lymphoid malignancies (Table 18.1) . Significant geographical and racial differences in the incidence of these disorders have been reported with a higher incidence in East Asia and in individuals of native American descent in Mexico, central and south America . With the availability of modern immunophenotypic and molecular tools, a better distinction of these disorders from their B-cell counterparts has been possible. Similarly, identification of recurrent cytogenetic and molecular abnormalities has shed further light on the pathogenesis of these neoplasms.
Table 18.1WHO classification of mature T and natural killer (NK) neoplasms |Favorite Table|Download (.pdf) Table 18.1 WHO classification of mature T and natural killer (NK) neoplasms
T-cell prolymphocytic leukaemia
T-cell large granular cell leukaemia
Aggressive NK cell leukaemia
Adult T-cell leukaemia/lymphoma
Primary cutaneous anaplastic
Large cell lymphoma
Extranodal NK/T-cell lymphoma, nasal type
Enteropathy-type T-cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Angioimmunoblastic T-cell lymphoma
Peripheral T-cell lymphoma, unspecified
Anaplastic large cell lymphoma
Neoplasms of uncertain lineage
Blastic NK cell lymphoma
In general, T-cell lymphomas and leukaemias are an aggressive group of neoplasms and respond poorly to traditional therapeutic modalities. However, recent development of new therapeutic agents such as alemtuzumab and the reasonable efficacy of nucleoside analogues such as cladribine, 2'deoxycoformycin (DCF) ...