Risk stratification in chronic lymphocytic leukemia
Primary source: International CLL-IPI working group. Lancet Oncol 2015; 16(8): e348-e358
CLL-IPI (Chronic Lymphocytic Leukemia International Prognostic Index, International CLL-IPI Working Group, Lancet Oncol 2016) is an international prognostic index for chronic lymphocytic leukemia. It combines 5 independent risk factors: TP53 status (mutation and/or del17p — 4 points), IGHV status (unmutated — 2 points), β2-microglobulin > 3.5 mg/L (2), stage (Rai I–IV or Binet B–C — 1), age > 65 years (1).
Stratification: 0–1 point — low risk (5-year survival 93%); 2–3 — intermediate (79%); 4–6 — high (63%); 7–10 — very high (23%). The score supports decisions on starting therapy (low risk is often managed with watch and wait), choice of agent (BCR inhibitors vs chemoimmunotherapy), and monitoring intensity.
In the era of targeted therapy (ibrutinib, acalabrutinib, venetoclax), the prognostic value of CLL-IPI has decreased somewhat — high-risk patients can achieve durable remissions on BTK inhibitors. Nonetheless, the score remains a standard stratification tool per ESMO 2023 guidelines.
72-year-old man with newly diagnosed CLL. Binet stage B (lymphadenopathy, no anemia or thrombocytopenia). TP53 unmutated, IGHV unmutated, β2-microglobulin 4.1 mg/L.
TP53 unmutated (0) + IGHV unmutated (2) + β2-microglobulin > 3.5 (2) + Binet stage B (1) + age > 65 (1) = 6 points.
High risk (4–6 points, 5-year survival ~63% in the pre-targeted-therapy era). Management: if criteria for active disease are met (progressive lymphadenopathy, hepatosplenomegaly, cytopenia, B symptoms) — start a BTK inhibitor (ibrutinib, acalabrutinib) or venetoclax + obinutuzumab; chemoimmunotherapy (FCR, BR) is now second-line. If disease is inactive — observation with reassessment every 3 months.
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