Chronic lymphocytic leukemia (CLL) - Then and Now
Publication Date
2016
Journal Title
Am J Hematol
Abstract
The field of chronic lymphocytic leukemia (CLL) has witnessed considerable change since the time clinical staging was introduced in clinical practice in 1975. Over the years, the prognostication in CLL has expanded with the addition in late 90s of mutational status of variable region of immunoglobulin heavy chain (IGHV), and chromosomal analyses using fluorescent in-situ hybridization (FISH). More recently, stereotypy of BCR (B cell receptor) and whole exome sequencing (WES) based discovery of specific mutations such as NOTCH1, TP53, SF3B1, XPO-1, BIRC3, ATM and RPS15 further refined the current prognostication system in CLL. In therapy, the field of CLL has seen major changes from oral chlorambucil and steroids prior to 1980s, to chemo-immunotherapy (CIT) with fludarabine, cyclophosphamide, rituximab (FCR) to the orally administered targeted therapeutic agents inhibiting kinases in the B cell receptor (BCR) signaling pathway such as Ibrutinib (BTK inhibitor) and Idelalisib (p110 PI3Kdelta inhibitor) and novel anti-CD20 mAb's (monoclonal antibodies) such as obinutuzumab. This progress is continuing and other targeted therapeutics such as Bcl2 antagonists (Venetoclax or ABT-199) and finally chimeric antigen receptor against T cells (CART) are developed. This review is an attempt to summarize the major benchmarks in the prognostication and in the therapy of CLL. This article is protected by copyright. All rights reserved.
Volume Number
91
Issue Number
3
Pages
330-40
Document Type
Article
EPub Date
2015/12/23
Status
Faculty
Facility
School of Medicine
Primary Department
Hematology/Medical Oncology
Additional Departments
Molecular Medicine
PMID
DOI
10.1002/ajh.24282