Table 2.
Covariate effect in each transition-specific model.
| Covariate | Transition 1: evolution in overt PMF | Transition 2: evolution in AML | Transition 3: death | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
| Clinicala | ||||||
| Male sex | 0.91 (0.44–1.87) | 0.790 | 0.34 (0.08–1.46) | 0.147 | 1.66 (0.64–4.26) | 0.296 |
| Age >65 years | 0.56 (0.25–1.30) | 0.176 | 10.3 (2.33–45.6) | 0.002 | 6.53 (2.38–17.9) | <0.0001 |
| Anemiab | 2.18 (1.01–4.72) | 0.047 | 1.34 (0.31–5.92) | 0.695 | 2.30 (0.88–5.37) | 0.153 |
| WBC > 15 × 109/L | 0.91 (0.29–2.84) | 0.870 | 4.80 (1.22–18.9) | 0.025 | 3.49 (1.35–9.01) | 0.010 |
| Plt > 1000 × 109/L | 1.96 (0.64–5.97) | 0.236 | 0.47 (0.07–3.16) | 0.438 | 1.21 (0.30–4.84) | 0.786 |
| Fibrosis grade 1 | 3.20 (1.08–9.41) | 0.035 | 0.34 (0.09–1.29) | 0.112 | 2.96 (0.82–10.7) | 0.100 |
| Spleen size > 5 cm | 0.59 (0.17–2.05) | 0.404 | 2.59 (0.66–10.2) | 0.175 | 0.79 (0.25–2.53) | 0.694 |
| LDH > 1.5 | 1.58 (0.76–3.30) | 0.221 | 8.13 (1.46–45.2) | 0.017 | 0.84 (0.36–1.98) | 0.687 |
| Abnormal cytogenetics | 1.60 (0.64–4.00) | 0.310 | 6.92 (1.61–29.8) | 0.009 | 1.84 (0.71–4.76) | 0.209 |
| Mutationalc | ||||||
| Driver | ||||||
| JAK2V617F | 0.87 (0.04–17.4) | 0.925 | 0.12 (0.02–6.00) | 0.286 | 0.82 (0.07–10.2) | 0.875 |
| MPLW515L/K | 0.93 (0.06–14.4) | 0.955 | 0.52 (0.01–24.7) | 0.740 | 1.91 (0.21–17.8) | 0.570 |
| CALR | 0.91 (0.06–14.4) | 0.955 | 0.13 (0.02–7.27) | 0.319 | 0.36 (0.04–3.68) | 0.390 |
| Triple negatives | 2.70 (0.10–74.3) | 0.557 | 0.13 (0.00–10.6) | 0.368 | 3.31 (0.23–46.6) | 0.376 |
| Nondriver | ||||||
| HMRd | 3.15 (1.08–9.21) | 0.036 | – | – | 4.62 (2.09–10.2) | <0.0001 |
| HMRe 2 | – | – | 6.62 (1.11–39.3) | 0.038 | – | – |
All transitions assume a Weibull baseline function.
HR hazard ratio, CI confidence interval, Hb hemoglobin, Hct hematocrit, Plt platelets, WBC white blood cell, LDH lactate dehydrogenase, HMR high molecular risk
aMultivariate models also corrected for treatment effect (chemotherapy yes/no; antiplatelets yes/no; anticoagulants yes/no).
bAnemia was defined for values of Hb < 12 g/dL for females and Hb < 13 g/dL for males.
cMultivariate models best fitted with HMR or HMR 2 alternatively.
dHMR, high molecular risk, points to the presence of at least one mutation in any one of ASXL1, EZH2, SRSF2, and IDH1/2.
eHMR 2 means the presence of 2 or more mutated genes among the above. Two or more mutations in the same gene are counted as one.
Significant P-values (P < 0.05) are indicated in bold.