Risk factors for evolution to MPN-BP
| Risk factor . | Comments . | Reference . |
|---|---|---|
| Clinicopathologic | Cumulative incidence >20 y for MPN-BP: 3.8%, 6.8%, and 14.2% in ET, PV, and PMF, respectively, in contemporary series from the Mayo clinic; evolution to overt MF phenotype often precedes MPN-BF in PV; in post-PV MF, high circulating CD34 counts; platelet count <100 × 109/L implicated in MPN-BP; median age at diagnosis: 61, 60, and 65 y for PV, ET, and MF, respectively | 12,15,16,19,33,95,96 |
| MPN subtype | ||
| PMF | ||
| Post-ET MF | ||
| Post-PV MF | ||
| Cytoreductive agents | Controversy regarding leukemogenic potential of hydroxyurea in the MPNs, which is not supported by evidence from large retrospective series | 15,19,,,,-24 |
| Phosphorus-32 | ||
| Chlorambucil | ||
| Piprobroman | ||
| Busulphan | ||
| Laboratory parameters | Blasts ≥3% + platelets <100 × 109/L indicates high risk for MPN-BP; blasts ≥10% + platelets <50 × 109/L indicates accelerated disease/very high risk for MPN-BP; transfusion dependency; WBC >30 × 109/L; WBC >15 × 109/L + age >61 y + abnormal karyotype (in PV) | 13,14,17,-19 |
| Circulating blasts | ||
| Anemia | ||
| Leukocytosis | ||
| Thrombocytopenia | ||
| Molecular/genetic | Unfavorable karyotype in DIPSS-plus: +8, −7/7q, i(17q), −5/5q−, 12p−, inv(3), and 11q23 or chromosome 5, 7, or 17p abnormalities indicates >6× risk of MPN-BP | 18,26,27,29,,-32 |
| Unfavorable karyotype (PMF) | ||
| 17p deletion | ||
| Mutations | ||
| ASXL1, IDH1/2, EZH2, SRSF2 | ||
| TET2, TP53 | ||
| Absence of CALR (in PMF) | ||
| ≥2 mutations | ||
| Germ line duplication of ATG2B/GSKIP* | ||
| Prognostic scoring systems (PMF) | In DIPSS, high risk for evolution to MPN-BP indicated by 7.8 for intermediate-2–risk disease and 24.9 for high-risk disease when compared with low risk; in DIPSS-plus, unfavorable karyotype + platelet count <100 000/uK indicates high risk for MPN-BP; MIPSS70 very high-risk category: 23% developed MPN-BP (HR, 13.3) when compared with low risk | 25,28 |
| Higher-risk DIPSS score | ||
| DIPSS-plus score | ||
| High-risk MIPSS70 score | ||
| Very high-risk MIPSS70-plus score† |
| Risk factor . | Comments . | Reference . |
|---|---|---|
| Clinicopathologic | Cumulative incidence >20 y for MPN-BP: 3.8%, 6.8%, and 14.2% in ET, PV, and PMF, respectively, in contemporary series from the Mayo clinic; evolution to overt MF phenotype often precedes MPN-BF in PV; in post-PV MF, high circulating CD34 counts; platelet count <100 × 109/L implicated in MPN-BP; median age at diagnosis: 61, 60, and 65 y for PV, ET, and MF, respectively | 12,15,16,19,33,95,96 |
| MPN subtype | ||
| PMF | ||
| Post-ET MF | ||
| Post-PV MF | ||
| Cytoreductive agents | Controversy regarding leukemogenic potential of hydroxyurea in the MPNs, which is not supported by evidence from large retrospective series | 15,19,,,,-24 |
| Phosphorus-32 | ||
| Chlorambucil | ||
| Piprobroman | ||
| Busulphan | ||
| Laboratory parameters | Blasts ≥3% + platelets <100 × 109/L indicates high risk for MPN-BP; blasts ≥10% + platelets <50 × 109/L indicates accelerated disease/very high risk for MPN-BP; transfusion dependency; WBC >30 × 109/L; WBC >15 × 109/L + age >61 y + abnormal karyotype (in PV) | 13,14,17,-19 |
| Circulating blasts | ||
| Anemia | ||
| Leukocytosis | ||
| Thrombocytopenia | ||
| Molecular/genetic | Unfavorable karyotype in DIPSS-plus: +8, −7/7q, i(17q), −5/5q−, 12p−, inv(3), and 11q23 or chromosome 5, 7, or 17p abnormalities indicates >6× risk of MPN-BP | 18,26,27,29,,-32 |
| Unfavorable karyotype (PMF) | ||
| 17p deletion | ||
| Mutations | ||
| ASXL1, IDH1/2, EZH2, SRSF2 | ||
| TET2, TP53 | ||
| Absence of CALR (in PMF) | ||
| ≥2 mutations | ||
| Germ line duplication of ATG2B/GSKIP* | ||
| Prognostic scoring systems (PMF) | In DIPSS, high risk for evolution to MPN-BP indicated by 7.8 for intermediate-2–risk disease and 24.9 for high-risk disease when compared with low risk; in DIPSS-plus, unfavorable karyotype + platelet count <100 000/uK indicates high risk for MPN-BP; MIPSS70 very high-risk category: 23% developed MPN-BP (HR, 13.3) when compared with low risk | 25,28 |
| Higher-risk DIPSS score | ||
| DIPSS-plus score | ||
| High-risk MIPSS70 score | ||
| Very high-risk MIPSS70-plus score† |
DIPSS, Dynamic International Prognostic Scoring System; HR, hazard ratio; MIPSS, Mutation-Enhanced International Prognostic Score System; WBC, white blood cell.
Associated with a familial MPN phenotype with high risk of MF and MPN-BP evolution.
Unfavorable karyotype in MIPSS70-plus: any abnormal karyotype other than normal karyotype or sole abnormalities of 20q−, 13q−, +9, chromosome 1 translocation/duplication, or sex chromosome abnormality other than −Y.