A 65-year-old man has splenomegaly, leukocytosis (WBC 90,000), and peripheral blood shows numerous mature lymphocytes with smudge cells. Flow cytometry reveals CD5+, CD19+, CD23+, CD20 dim, surface Ig dim, FMC7-. The CLL International Prognostic Index (CLL-IPI) incorporates which molecular marker as the STRONGEST adverse independent prognostic factor?
- A TP53 mutation/deletion (del17p) ✓
- B IGHV unmutated status
- C ZAP-70 positivity by flow cytometry
- D Trisomy 12 by FISH
Explanation
In the CLL International Prognostic Index (CLL-IPI), TP53 mutation/deletion (del17p or TP53 mutation) carries the highest independent hazard ratio for overall survival (~3.8) among all biological variables, including IGHV mutation status, serum beta-2 microglobulin, Binet/Rai staging, and IGHV. Del17p and TP53 mutations predict resistance to chemoimmunotherapy (fludarabine-based regimens) and mandate upfront targeted therapy with ibrutinib or venetoclax+obinutuzumab. IGHV unmutated status is prognostically adverse but has a lower hazard ratio; ZAP-70 is a surrogate for IGHV unmutated status and is less precise; trisomy 12 has intermediate prognosis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.