Canterbury DHB

Prognosis

There are several prognostic scores to predict outcomes in PMF as below. DIPSS plus is a modern prognostic model which incorporates molecular information. See Rumi E, et al. (2017),¹ table 6 page 9.

It is well established that the driver mutation has an impact on outcome in PMF as per the figure below:

• A JAK2 mutation is detected in approximately 60% of patients.
• The calreticulin gene (CALR) is mutated in 20%.
• The myeloproliferative leukemia virus (MPL) gene is mutated in 5%.

Patients with mutated CALR and MPL genes have a favourable outcome, compared to those with JAK2 mutations, but patients who are triple negative appear to have the worst outcome, see Rumi E, et al. (2017),¹ figure 4 page 10.

Vannucchi AM, et al. (2014)² described a mutation-enhanced International Prognostic Scoring System (MIPSS) for Primary Myelofibrosis, including the mutations of:

• JAK2
• MPL
• CAL-R
• EZH2
• ASXL1
• IDH1/2
• SRSF2

In this scoring system, the following were found to be significant risk factors for poor survival:

• aged > 60 years
• constitutional symptoms
• hb < 100 g/L
• platelet count <200 × 109 /L
• triple-negative mutation status
• JAK2 or MPL mutation
• ASXL1 or SRSF2 mutations

By calculation of MIPSS, four risk groups are clearly delineated:

• low (score 0-0.5)
• intermediate-1 (score 1-1.5)
• intermediate-2 (score 2-3.5)
• high (score 4 or greater)

See Vannucchi AM, et al. (2014),² figure 1 for:

• numbers in each group
• median survival
• haematological response (HR) outcomes.

Leukemia-free survival was also predicted by high (p<0.01) and intermediate 1/2 (p<0.01) risk MIPSS.

An extended molecular panel may be useful, especially when considering the benefit of allogeneic transplant. As of July 2018, extended molecular testing is not available in New Zealand, but the required genes for MIPSS can be requested from the Peter MacCallum Cancer Centre in Melbourne, Australia (myeloid panel cost approx. AUD600.00 + transport).

Topic Code: 6243