Chronic lymphocytic leukemia (CLL)-Then and now

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Chronic lymphocytic leukemia (CLL) management has transformed since the 1970s.
• Prognostic markers have advanced from clinical staging to include IGHV mutational status, FISH, and gene sequencing.
• Therapeutic strategies have shifted from chemotherapy to targeted agents and immunotherapy.

Purpose of the Study:

• To review major advancements in CLL prognostication.
• To summarize key developments in CLL therapy.
• To provide historical context for current CLL understanding and treatment.

Main Methods:

• Literature review of key studies and clinical trials in CLL.
• Analysis of historical and recent data on prognostic markers.
• Overview of therapeutic evolution in CLL treatment.

Main Results:

• Prognostication refined by IGHV, FISH, BCR stereotypy, and mutations (NOTCH1, TP53, etc.).
• Therapy evolved from chlorambucil to chemo-immunotherapy (FCR), targeted agents (Ibrutinib, Idelalisib), and novel antibodies (Obinutuzumab).
• Emerging therapies include Bcl2 antagonists (Venetoclax) and CAR-T cells.

Conclusions:

• Significant progress in understanding CLL biology and patient stratification.
• Targeted therapies and novel agents have dramatically improved CLL treatment outcomes.
• Continued research promises further advancements in CLL management.