Triple A Plus (AAA+) Survival Prediction Model for Essential Thrombocythemia: Analysis Involving 7308 Patients

Survival prediction models in essential thrombocythemia (ET) include the International Prognostic Scoring System (IPSET) and the more recently introduced triple-A (AAA) prognostic score. The latter enlists age and absolute neutrophil (ANC) and lymphocyte (ALC) counts as risk variables. In the current study, a Mayo Clinic discovery cohort of 658 patients with ET was used to identify AAA-independent risk variables. Accordingly, multivariable analysis-derived HRs (95% CI) were 15.7 (8.4-29.5) for age > 70 years (8 points); 4.2 (2.3-7.5) for age 50 to 70 years (2 points); 1.8 (1.2-2.5) for ANC >= 8 x 10(9)/L (1 point); 1.4 (1.03-1.9) for ALC < 1.7 x 10(9)/L (1 point); 1.8 (1.2-2.6) for absolute monocyte count (AMC) >= 0.5 x 10(9)/L (1 point); 1.8 (1.2-2.3) for male sex (1 point); 1.8 (1.3-2.4) for arterial hypertension (1 point); and 1.6 (1.2-2.3) for arterial thrombosis (1 point). HR-weighted scoring enabled a 4-tiered risk classification: ultra-low (0-1 points; N = 94; median survival 42.7 years), low (2-4 points; N = 297; 23 years), intermediate (5 points; N = 66; 17.3 years), and high (6-14 points; N = 201; 10.8 years). Time-dependent predictive performance at 20/25 years favored AAA(+) (AUC 0.92/0.91) vs. AAA (0.86/0.86) vs. IPSET (0.81/0.84). The AAA(+) risk model was subsequently validated by two external cohorts from Israel (N = 5968) and Italy (N = 682). In the cohort from Israel, disease-specific mortality was assessed by comparing observed survival to an age- and sex-matched reference population, which suggested near-normal life expectancy in ultra-low risk patients. The current study highlights host-related factors as the primary determinants of longevity in ET and provides a composite risk score (AAA(+)) that is based on complete blood count-derived parameters and host-related factors. Predictive performance of the new model was shown to be superior to that of IPSET and AAA.