PAGE CONTENTS

Prognosis

Myelofibrosis (MF) involves the clonal proliferation of hematopoietic stem cells in the bone marrow, which leads to cytokine release and bone marrow fibrosis. The prognosis or disease course may vary among patients with MF. While some patients remain stable for long periods with minimal interruptions due to the disease, others may experience rapid disease progression and require regular blood transfusions or drug treatments. In around 10% to 20% of cases, the disease may progress to acute myeloid leukemia.^1-3 The median survival time, which was around 6.5 years before 2007, has improved in the last decade with the introduction of Janus kinase (JAK) inhibitors.⁴

Prognostic Scoring Systems

Several prognostic scoring systems have been developed to predict survival and guide therapeutic decisions. The most common prognostic scoring systems used for the risk stratification of patients with MF are the International Prognostic Scoring System (IPSS), Dynamic International Prognostic Scoring System (DIPSS), and DIPSS-Plus (DIPSS+). Other prognostic models, which consider mutational status and/or cytogenetic information, have been developed to refine the risk stratification. These models include the Mutation-enhanced International Prognostic Scoring System 70 (MIPSS70), MIPSS70-Plus (MIPSS70+), MIPSS70+ version 2.0, and Genetically Inspired Prognostic Scoring System (GIPSS).^5,6

Prognostic Scoring Systems for Basic Risk Stratification of PMF

IPSS

The IPSS was developed in 2009 for risk stratification at the time of initial diagnosis of primary myelofibrosis (PMF). This scoring system incorporates 5 independent predictors of inferior survival⁷:

Age >65 years
Hemoglobin level <10g/dL
Leukocyte count >25×10⁹ /L
Circulating blast cells ≥1%
Presence of constitutional symptoms

The IPSS stratifies patients into 4 different risk groups at diagnosis based on the number of adverse factors: low risk (0 adverse factors), intermediate-1 risk (1 adverse factor), intermediate-2 risk (2 adverse factors), and high risk (3 or more adverse factors). The corresponding median survival times are 135 months, 95 months, 48 months, and 27 months, respectively.⁷

Read more about MF types

DIPSS

The DIPSS is a dynamic risk stratification system that can be used at any point during the course of disease. It was developed using the same prognostic variables as in the IPSS except that 2 points (instead of 1 point) were assigned for hemoglobin <10 g/dL⁸:

Age >65 years (1 point)
Hemoglobin level <10 g/dL (2 points)
Leukocyte count >25×10⁹ /L (1 point)
Circulating blast cells ≥1% (1 point)
Presence of constitutional symptoms (1 point)

The DIPSS stratifies patients into 4 different risk groups: low risk (0 adverse points), intermediate-1 risk (1 or 2 points), intermediate-2 risk (3 or 4 points), and high risk (5 or 6 points). Median survival was not reached in the low-risk group. It was 14 years, 4 years, and 1.5 years in the intermediate-1-, intermediate-2-, and high-risk groups, respectively.⁸

DIPSS+

The DIPSS+ is a modified form of DIPSS that incorporates additional prognostic information from karyotype, transfusion dependence status, and platelet count to predict overall survival in patients with MF⁹:

Age >65 years
Hemoglobin level <10 g/dL
Leukocyte count >25×10⁹ /L
Circulating blast cells ≥1%
Presence of constitutional symptoms
Platelet count <100×10⁹/L
Need for red blood cell transfusion
Unfavorable karyotype (complex karyotype or 1 or 2 abnormalities that include +8, -7/7q-, i[17q], -5/5q-, 12p-, inv[3], or 11q23 rearrangement)

Based on these 8 risk factors, DIPSS+ stratifies patients into 4 risk groups: low risk (no risk factors), intermediate-1 risk (1 risk factor), intermediate-2 risk (2 or 3 risk factors), and high risk (4 or more risk factors). The respective median survival times are 15 years, 6.7 years, 2.9 years, and 1.3 years.⁹

Read more about MF risk factors

Prognostic Scoring Systems for Advanced Risk Stratification

MIPSS70

The MIPSS70 integrates clinical and mutation data to predict survival in patients with MF who are eligible for transplantation (aged ≤70 years). Subsequent versions of the MIPSS70 — MIPSS70+ and MIPSS70+ version 2.0 — incorporate cytogenetic information in addition to clinical risk factors and mutations. An online score calculator is available for the MIPSS70 and MIPSS70+ version 2.0.¹⁰

The MIPSS70 is based on 3 genetic variables and 6 clinical risk factors¹¹:

Absence of a CALR type 1/like mutation
High molecular risk (HMR) category: presence of any HMR mutation, specifically ASXL1, SRSF2, EZH2, or IDH1/IDH2
Presence of 2 or more HMR mutations
Hemoglobin <10 g/dL
Leukocyte count >25×10⁹ /L
Platelet count <100×10⁹ /L
Circulating blasts ≥2%
Bone marrow fibrosis grade ≥2
Presence of constitutional symptoms

This scoring system was developed to evaluate the risk involved in transplantation and facilitate transplant decision-making in patients aged 70 years and under. The MIPSS70 stratifies patients into 3 risk categories — low risk, intermediate risk, and high risk — with 5-year overall survival rates of 95%, 70%, and 29%, respectively.¹¹

Read more about MF surgical management

MIPSS70+

The MIPSS70+ prognostic model considers cytogenetic information but does not include factors of bone marrow fibrosis grade, leukocyte count, or platelet count¹¹:

Absence of a CALR type1/like mutation
High molecular risk (HMR) category: presence of any HMR mutation, specifically ASXL1, SRSF2, EZH2, or IDH1/IDH2
Presence of 2 or more HMR mutations
Unfavorable karyotype
Hemoglobin level <10g/dL
Circulating blasts ≥2%
Presence of constitutional symptoms

This system stratifies patients into 4 risk categories — low risk, intermediate risk, high risk, and very high risk — with 5-year overall survival rates of 91%, 66%, 42%, and 7%, respectively.¹¹

Read more about MF guidelines

MIPSS70+ Version 2.0

The MIPSS70+ version 2.0 incorporates cytogenetic risk factors, includes U2AF1 Q157 as an additional HMR mutation, and specifies sex- and severity-adjusted hemoglobin threshold values. It includes 5 genetic variables¹²:

Very high risk (VHR) karyotype (single or multiple abnormalities of -7, i[17q], inv[3], 12p-, 11q-, and autosomal trisomies other than +8 or +9)
Unfavorable karyotype (all other abnormalities)
Presence of 2 or more HMR mutations
Presence of 1 HMR mutation
Absence of a CALR type 1/like mutation

It also includes 4 clinical variables¹²:

Severe anemia (hemoglobin level <8 g/dL in women and <9 g/dL in men)
Moderate anemia (hemoglobin level 8-9.9 g/dL in women and 9-10.9 g/dL in men)
Circulating blasts ≥2%
Presence of constitutional symptoms

The MIPSS70+ version 2.0 stratifies patients into 5 risk categories — very low risk, low risk, intermediate risk, high risk, and very high risk — with median overall survival times of not reached, 10.3 years, 7 years, 3.5 years, and 1.8 years, respectively. The 10-year survival rates were 86%, 50%, 30%, 10%, and <3%, respectively.¹²

Read more about MF epidemiology

GIPSS

The GIPSS is exclusively based on mutational status and karyotype. In a study of 641 patients with primary MF whose information on cytogenetics and mutational status was available, multivariate analysis identified VHR karyotype, unfavorable karyotype, absence of a CALR type 1/like mutation, and the presence of ASXL1, SRSF2, or U2AF1 Q157 mutations as predictors of inferior survival. Based on the aforementioned risk factors, the GIPSS stratified patients into 4 risk categories: low risk, intermediate-1 risk, intermediate-2 risk, and high risk. The corresponding median 5-year survival rates were 94%, 73%, 40%, and 14%, respectively.¹³

Prognostic Scoring for Risk Stratification of Secondary MF

MYSEC-PM

The Myelofibrosis Secondary to Polycythemia Vera (PV) and Essential Thrombocythemia (ET)-Prognostic Model (MYSEC-PM) is recommended for risk stratification of patients with MF secondary to PV or ET. The model is based on the following risk factors¹⁴:

Age
Hemoglobin level <11 g/dL
Circulating blasts ≥3%
CALR mutation status
Platelet count <150×10⁹/L
Presence of constitutional symptoms

The MYSEC-PM classifies patients with post-PV or post-ET MF into 4 risk groups: low risk, intermediate-1 risk, intermediate-2 risk, and high risk. The corresponding median survival times were not reached, 9 years, 4 years, and 2 years, respectively.¹⁴

Read more about MF comorbidities

References

Primary myelofibrosis. Leukaemia Foundation. Updated June 29, 2020. Accessed December 27, 2022.
Myelofibrosis (MF) prognosis. Blood Cancer UK. Accessed December 27, 2022.
Lal A. Primary myelofibrosis: prognosis. Medscape. Updated September 21, 2022. Accessed December 27, 2022.
Masarova L, Bose P, Pemmaraju N, et al. Improved survival of patients with myelofibrosis in the last decade: single-center experience. Cancer. 2022;128(8):1658-1665. doi:10.1002/cncr.34103
Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021;96(1):145-162. doi:10.1002/ajh.26050
Gerds AT, Gotlib J, Ali H, et al. Myeloproliferative neoplasms, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(9):1033-1062. doi:10.6004/jnccn.2022.0046
Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901. doi:10.1182/blood-2008-07-170449
Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-1708. doi:10.1182/blood-2009-09-245837
Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392-397. doi:10.1200/JCO.2010.32.2446
MIPSS70 score. MIPSS70score.it. Accessed December 27, 2022.
Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: Mutation-enhanced International Prognostic Score System for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2018;36(4):310-318. doi:10.1200/JCO.2017.76.4886
Tefferi A, Guglielmelli P, Lasho TL, et al. MIPSS70+ version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol. 2018;36(17):1769-1770. doi:10.1200/JCO.2018.78.9867
Tefferi A, Guglielmelli P, Nicolosi M, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia. 2018;32(7):1631-1642. doi:10.1038/s41375-018-0107-z
Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31(12):2726-2731. doi:10.1038/leu.2017.169

Reviewed by Kyle Habet, MD, on 12/24/2022.

Erum Naqvi, PhD

Erum Naqvi obtained her Ph.D. in Molecular Medicine from Hannover Medical School (Germany) after completing her Masters in Biomedical Science and Bachelors in Microbiology from University of Delhi (India). She has several years of experience as a science writer.

Myelofibrosis (MF)