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Genetically Inspired Prognostic Scoring System (GIPSS) for PMF

Predicts overall survival in primary myelofibrosis using karyotype and somatic mutation data

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Why use it

GIPSS provides a purely genetic prognostic assessment independent of clinical variables (blood counts, symptoms, splenomegaly), making it uniquely useful when clinical data is confounded by prior therapy, transfusions, or hypersplenism. It complements the IPSS/DIPSS/DIPSS-Plus systems and is directly applicable at diagnosis and at any disease timepoint. GIPSS also guides transplant decision-making: intermediate-2 and high-risk patients are candidates for allogeneic stem cell transplantation.

About

The Genetically Inspired Prognostic Scoring System (GIPSS) for Primary Myelofibrosis (PMF) was developed by Tefferi and colleagues at Mayo Clinic and published in 2018. Unlike clinical scoring systems such as IPSS and DIPSS, GIPSS relies exclusively on genetic data — karyotype and somatic mutation profile — without incorporating any clinical or laboratory variables. This makes it uniquely applicable across the entire disease course and independent of treatment effects on blood counts. GIPSS stratifies patients into four risk categories based on the presence of: (1) unfavorable karyotype (monosomal karyotype, trisomy 8, i(17q), inv(3)/3q21, 12p−, 11q23/11q−, or other autosomal trisomies); (2) absence of CALR type 1 or type 1-like mutation; (3) presence of high molecular risk (HMR) mutations in ASXL1, EZH2, SRSF2, IDH1/IDH2; and (4) presence of two or more HMR mutations. GIPSS was validated in a large international cohort and shows strong discrimination for overall survival across risk tiers.

When to use

  • At diagnosis of primary myelofibrosis when karyotype and molecular data are available
  • At any disease timepoint to reassess prognosis after acquisition of new mutations
  • When clinical variables are confounded by transfusion or treatment effects
  • To complement IPSS/DIPSS prognostication for transplant decision-making
  • In multidisciplinary hematology team discussions for PMF management planning

Formula

GIPSS Score: +1 point: Unfavorable karyotype +1 point: Absence of CALR type 1/type 1-like mutation +1 point: Presence of ≥1 HMR mutation (ASXL1, EZH2, SRSF2, IDH1, IDH2) +1 point: Presence of ≥2 HMR mutations (Maximum possible: 4 points) Risk Categories: 0 points: Low risk (median OS ~26 years) 1 point: Intermediate-1 (median OS ~8 years) 2 points: Intermediate-2 (median OS ~4 years) ≥3 points: High risk (median OS ~2 years)

Pearls & pitfalls

  • GIPSS is the ONLY major PMF prognostic score that uses EXCLUSIVELY genetic data — no CBC, no symptoms, no splenomegaly required.
  • CALR type 1/type 1-like mutation (52-bp deletion) confers a favorable prognosis and is the only "protective" genetic variable in GIPSS.
  • HMR mutations (ASXL1, EZH2, SRSF2, IDH1/IDH2) each confer 1 point; having 2+ HMR mutations adds an additional point (total 2 for that component).
  • Unfavorable karyotype in GIPSS includes: monosomal karyotype, +8, i(17q), inv(3)/3q21, 12p−, 11q−/11q23 rearrangement, or other autosomal trisomies.
  • Normal karyotype and sole 20q−, 13q−, or chromosome 1 translocation/duplication are NOT unfavorable in GIPSS.
  • CALR type 2 mutation (5-bp insertion) does NOT confer favorable prognosis — only type 1/type 1-like does.
  • Triple-negative PMF (JAK2/CALR/MPL wild-type) is associated with poor prognosis and high HMR mutation frequency.
  • GIPSS should be used alongside DIPSS-Plus in clinical practice for comprehensive risk stratification.

Next steps

Low Risk: Observation or symptom-directed therapy. Median survival >10 years. Transplant not indicated based on GIPSS alone. Intermediate-1 Risk: Active symptom management; consider clinical trial enrollment. Intermediate-2 Risk: Consider allogeneic SCT evaluation, especially in patients ≤70 years. High Risk: Allogeneic SCT strongly recommended for eligible patients. Median survival approximately 2 years without transplant.

Evidence

Tefferi A et al. Genetically inspired prognostic scoring system for primary myelofibrosis (GIPSS) based solely on mutation and karyotype information. Leukemia. 2018;32(7):1631-1642. PMID:29540830. Training cohort: 641 patients; validation cohort: 336 patients. C-statistic 0.70. Median OS: Low 26.4 yr, Int-1 8.0 yr, Int-2 4.2 yr, High 2.0 yr.

References

  1. Tefferi A et al. Genetically inspired prognostic scoring system for primary myelofibrosis (GIPSS) based solely on mutation and karyotype information. Leukemia. 2018;32(7):1631-1642. — link
  2. Tefferi A et al. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(5):801-821. — link
  3. Guglielmelli P et al. MIPSS70+: Mutation- and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis. J Clin Oncol. 2018;36(4):310-318. — link