MIPSS-PV Scoring System: Purpose and Application in Myeloproliferative Neoplasms
The MIPSS-PV (Myeloproliferative Neoplasm International Prognostic Score System) is a comprehensive risk stratification tool designed to predict survival outcomes and guide treatment decisions in patients with myelofibrosis, particularly focusing on transplantation-age patients with primary myelofibrosis (PMF).
Overview of Myeloproliferative Neoplasm Prognostic Systems
Evolution of Prognostic Models
- Traditional prognostic systems for PV and ET focused primarily on thrombosis risk using age and thrombosis history 1
- For myelofibrosis, risk stratification has evolved from clinical-only models to integrated genetic-clinical models
Established Prognostic Systems for Myelofibrosis
- International Prognostic Scoring System (IPSS) - baseline assessment at diagnosis 1
- Dynamic IPSS (DIPSS) - can be applied at any time during disease course 1
- DIPSS-plus - incorporates cytogenetics, platelet count, and transfusion status 2
MIPSS70 and MIPSS70-plus Systems
Components and Risk Factors
MIPSS70 integrates the following risk factors 3:
Clinical factors:
- Hemoglobin < 100 g/L
- Leukocytes > 25 × 10^9/L
- Platelets < 100 × 10^9/L
- Circulating blasts ≥ 2%
- Bone marrow fibrosis grade ≥ 2
- Constitutional symptoms
Genetic factors:
- Absence of CALR type-1 mutation
- Presence of high-molecular risk mutations (ASXL1, EZH2, SRSF2, IDH1/2)
- Presence of two or more high-molecular risk mutations
Risk Categories and Survival Outcomes
MIPSS70 model defines three risk categories 3:
- Low risk: 5-year OS 95%, median OS 27.7 years
- Intermediate risk: 5-year OS 70%, median OS 7.1 years
- High risk: 5-year OS 29%, median OS 2.3 years
MIPSS70-plus (including cytogenetic information) defines four risk categories 3:
- Low risk: 5-year OS 91%
- Intermediate risk: 5-year OS 66%
- High risk: 5-year OS 42%
- Very high risk: 5-year OS 7%
Clinical Application and Treatment Implications
Treatment Decision Framework
Based on MIPSS70+ version 2.0 risk categories 4, 5:
- Very low/low risk: Observation alone (estimated 10-year survival 56%-92%)
- Intermediate risk: Consider clinical trials (estimated 10-year survival 30%)
- High/very high risk: Allogeneic hematopoietic stem cell transplantation (AHSCT) is preferred (estimated 10-year survival 0-13%)
Practical Implementation
Diagnostic workup:
- Bone marrow examination with cytogenetic studies
- Molecular testing for driver mutations (JAK2, CALR, MPL)
- Screening for high-molecular risk mutations (ASXL1, EZH2, SRSF2, IDH1/2)
Risk assessment:
- Apply MIPSS70 or MIPSS70-plus scoring
- Determine risk category
- Reassess risk periodically using dynamic models
Importance of Genetic Assessment
The European LeukemiaNet guidelines recommend 1:
- Complete genetic assessment for prognostic evaluation at diagnosis
- Cytogenetic studies and classification of CALR mutations
- Screening for non-driver mutations (at least ASXL1 and SRSF2)
Common Pitfalls and Caveats
- Incomplete genetic profiling: Failure to perform comprehensive genetic assessment may lead to inaccurate risk stratification
- Static vs. dynamic assessment: Remember that risk can change over time; DIPSS allows for reassessment during disease course
- Age considerations: MIPSS70 was developed specifically for transplant-age patients (≤70 years)
- Disease evolution: Approximately 15% of ET or PV patients may progress to post-ET/PV myelofibrosis, requiring reassessment 4
- Distinction between prefibrotic and overtly fibrotic PMF: These entities have different presentations and may require different management approaches
The MIPSS-PV scoring system represents a significant advancement in the personalized management of myelofibrosis patients by integrating clinical, cytogenetic, and molecular data to provide more accurate risk stratification and guide critical treatment decisions, particularly regarding the timing of stem cell transplantation.