CLL with del(17p) TP53 Loss MCQ — NEET PG Practice Question | NEETPGAI
CLL with del(17p) TP53 Loss
medium
stethoscope Medicine
A 62-year-old man presents with progressive fatigue, night sweats, and massive splenomegaly. Peripheral blood smear shows mature lymphocytes with smudge cells. Flow cytometry confirms CD5+CD19+CD23+ kappa-restricted B-cell clone (Matutes score 5). FISH panel reveals the abnormality marked **A** in the diagram. Which of the following is the MOST appropriate first-line therapeutic approach for this patient?
A. Ibrutinib monotherapy
B. Chlorambucil with observation
C. Bendamustine-rituximab (BR)
D. Fludarabine-cyclophosphamide-rituximab (FCR)
Explanation
Why Ibrutinib monotherapy is right
The abnormality marked A is del(17p13.1) with TP53 loss, the worst prognostic marker in CLL (median OS 2–3 years with chemoimmunotherapy). TP53 loss abolishes the G1/S checkpoint and DNA damage-induced apoptosis, conferring RESISTANCE TO CHEMOTHERAPY (fludarabine, cyclophosphamide, bendamustine) and anti-CD20 monoclonals alone. BTK inhibitors like ibrutinib (420 mg daily) are the standard first-line choice for del(17p) CLL, as they bypass the defective apoptotic machinery and induce cell death through alternative pathways. The iwCLL 2018 and NCCN 2024 guidelines explicitly recommend BTK inhibitors or BCL2 inhibitors (venetoclax + obinutuzumab) for del(17p) disease, avoiding chemotherapy entirely.
Why each distractor is wrong
Fludarabine-cyclophosphamide-rituximab (FCR): This is the classic chemoimmunotherapy regimen, but it is CONTRAINDICATED in del(17p) CLL because TP53 loss confers resistance to DNA-damaging agents and chemotherapy-induced apoptosis. FCR is ineffective and harmful in this setting.
Bendamustine-rituximab (BR): Like FCR, bendamustine is a DNA-alkylating agent. TP53 loss prevents apoptosis in response to DNA damage, making BR ineffective and inappropriate for del(17p) disease.
Chlorambucil with observation: Chlorambucil is an older alkylating agent with poor efficacy in CLL and is particularly ineffective in del(17p) disease. Observation without active therapy is inappropriate for a symptomatic patient with advanced Rai stage III/IV disease and bulky lymphadenopathy.
High-YieldNEET PG
del(17p) TP53 loss = AVOID chemotherapy; use BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) or venetoclax + obinutuzumab as first-line.
iwCLL 2018 Guidelines; NCCN CLL 2024
Practice similar questions
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.
