Novel agents and strategies for treatment of p53-defective chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is a common leukemia with a highly variable natural history. A subset of patients with high-risk CLL rapidly progress to develop symptomatic disease requiring treatment. Over-represented in this group are those who have a deletion of 17p13.1, the chromosomal location of the tumor suppressor gene P53. Of all prognostic factors examined in CLL, del(17p13.1) has a superior predictive value for poor response to conventional therapy. In this article we review the current published data on prognostic factors relevant to treatment in CLL. We next provide therapeutic recommendations for patients with del(17p13.1) that are available to oncologists in general practice. Chemoimmunotherapy, alemtuzumab, or high-dose corticosteroids are all effective as initial therapy for these patients, but progression is generally rapid. If allogeneic immune therapy is to be considered, it should be approached as part of initial or first salvage therapy. The investigational agent flavopiridol has also demonstrated clinical activity in this subset of patients. Identification of small molecules and new treatment approaches for patients with del(17p13.1) is a major focus of several investigators. Selection of therapy based on high-risk genomic features represents an appropriate treatment approach supported by currently available published data.
Grever
Michael R
MR
Division of Hematology-Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. michael.grever@osumc.edu
Lucas
David M
DM
Johnson
Amy J
AJ
Byrd
John C
JC
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand / Q000627:therapeutic use; D002886:Chromosomes, Human, Pair 17; D003131:Combined Modality Therapy; D005419:Flavonoids / Q000627:therapeutic use; D017353:Gene Deletion; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D005419:Flavonoids; D010880:Piperidines; D016159:Tumor Suppressor Protein p53; D023201:CD40 Ligand; D000074323:Alemtuzumab; C077990:alvocidib