Table 3.
Univariate and multivariable analysis of genetic risk factors for overall and leukemia-free survival among 641 patients with primary myelofibrosis
| Overall survival | ||
|---|---|---|
| Variables | Univariate analysis P-value (HR, 95% CI) | Multivariable analysis P-value (HR, 95% CI) |
| Revised cytogenetic risk model a | <0.001 | <0.001 |
| Very high risk karyotype | < 0.001 (3.6, 2.6–5.1) | < 0.001 (2.5, 1.7–3.5) |
| Unfavorable karyotype | <0.001 (1.9, 1.4–2.5) | <0.001 (1.9, 1.4–2.5) |
| Favorable karyotype | Reference | Reference |
| ASXL1-mutated | <0.001 (2.1, 1.7–2.6) | <0.001 (1.6, 1.3–2) |
| SRSF2-mutated | <0.001 (2.6, 1.9–3.3) | <0.001 (2.2, 1.7–2. |
| U2AF1Q157-mutated | <0.001 (2.6, 1.8–3.6) | 0.002 (1.9, 1.4–2.7) |
| EZH2-mutated | 0.2 (1.3, 0.8–1.9) | |
| IDH1 or IDH2-mutated | 0.07 (1.6, 0.9–2.6) | |
| Driver mutational status | <0.001 | <0.001 |
| JAK2 | <0.001 (2.3, 1.7–3.1) | <0.001 (2.2, 1.6–3.0) |
| MPL | 0.003 (2.3, 1.5–3.6) | 0.03 (1.6, 1.1–2.6) |
| Triple negative | <0.001 (2.9, 1.9–4.3) | <0.001 (2.3, 1.5–3.5) |
| Type 2/like CALR | 0.1 (1.6, 0.9–2.7) | |
| Type 1/like CALR | Reference | Reference |
| Type 1/like CALR absent | <0.001 (2.3, 1.7–3.1) | <0.001 (2.0, 1.5–2.8) |
| DIPSS b | <0.001 | < 0.001 |
| High | <0.001 (8.3, 5.2–13.3) | <0.001 (4.6, 2.8–7.4) |
| Intermediate-2 | <0.001 (5.6, 3.6–8.6) | <0.001 (4.2, 2.7–6.5) |
| Intermediate-1 | <0.001 (2.9, 1.9–4.5) | <0.001 (2.6, 1.7–4.1) |
| Low | Reference | Reference |
| Leukemia-free survival | ||
| Variables | Univariate analysis P (HR, 95%CI) | Multivariable analysis P (HR, 95%CI) |
| Revised cytogenetic risk model | <0.001 | 0.002 |
| Very high risk karyotype | <0.001 (4.6, 2.3–9.5) | 0.04 (2.4, 1.02–5.5) |
| Unfavorable karyotype | 0.005 (2.3, 1.3–4.1) | 0.0009 (2.7, 1.5–4.9) |
| Favorable karyotype | Reference | Reference |
| ASXL1-mutated | <0.001 (2.6, 1.6–4.1) | 0.004 (2.1, 1.3–3.4) |
| SRSF2-mutated | <0.001 (3.9, 2.3–6.7) | <0.001 (4.3, 2.5–7.5) |
| U2AF1Q157-mutated | 0.8 (1.1, 0.4–3.1) | |
| EZH2-mutated | 0.06 (2.0, 0.9–4.2) | |
| IDH1 or IDH2-mutated | 0.005 (3.1, 1.4–6.7) | |
| Driver mutational status | 0.04 | |
| JAK2 | 0.4 (1.3, 0.7–2.4) | |
| MPL | 0.4 (1.5, 0.6–4.0) | |
| Triple negative | 0.005 (2.9, 1.4–6.2) | |
| Type 2/like CALR | 0.1 (0.9, 0.3–3.5) | |
| Type 1/like CALR | Reference | |
| Type 1/like CALR absent | 0.2 (1.5, 0.8–2.6) | |
| Platelets <100 × 109/l | 0.007 (2.5, 1.5–4.2) | 0.002 (2.3, 1.3–4.0) |
| Circulating blasts ≥2% | <0.001 (3.3, 2.0–5.3) | 0.001 (2.6, 1.6–4.3) |
| DIPSS b | 0.005 | |
| High | 0.002 (7.2, 2.5–20.4) | |
| Intermediate-2 | 0.001 (4.9, 1.9–12.5) | |
| Intermediate-1 | 0.04 (2.7, 1.03–7.3) | |
| Low | ||
The values in bold indicate a significant P-value (<0.05)
ASXL1 additional sex combs like 1, SRSF2 serine/arginine-rich splicing factor 2, U2AF1 U2 small nuclear RNA auxiliary factor 1, EZH2 enhancer of zeste homolog 2, IDH1/2 isocitrate dehydrogenase 1/2, JAK2 Janus kinase 2, CALR calreticulin, MPL myeloproliferative leukemia virus oncogene
a Revised cytogenetic risk stratification: “very high risk (VHR)”—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, +21, or other autosomal trisomies, not including +8/+9; “favorable”—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including—Y; “unfavorable”—all other abnormalities (reference in the text)
b DIPSS, Dynamic International Prognostic Scoring System uses five independent predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 109/L, circulating blasts ≥1% and constitutional symptoms (reference in the text)