Primary Myelofibrosis - Episode 2

Risk Stratification for Patients With Myelofibrosis

Ruben A. Mesa, MD, FACP:This particular patient, if we use the DIPSS-plus [dynamic international prognostic scoring system plus] criteria, which is probably the most commonly used at the current time, would have several risk factors that would weigh in: Their age, being over age 65; the presence of anemia, a hemoglobin of less than 10; the presence of symptoms; and the presence of greater than 1% blasts. This individual would fall into the category of being intermediate-2 by that risk set of criteria.

Features that the patient did not have that would be additional factors that would make someone high risk would include transfusion dependence, a high-risk karyotype—this individual had a mutation in the 20th chromosome, which is not a high-risk mutation—or the presence of thrombocytopenia.

There are multiple classification systems and prognostic scores for myelofibrosis. Which one you can utilize is in part dependent on which of the variables you have available to you. Through the DIPSS, you can calculate by your physical exam, your symptom assessment, and a complete blood count. With the DIPSS-plus, we were able to calculate this patient because we also had the chromosomal analysis available, and this individual did not have a high-risk chromosome analysis.

The MIPSS70 [mutation-enhanced international prognostic scoring system for transplant-age patients] is for individuals under the age of 70. It is meant to inform for individuals who might be a candidate for stem cell transplantation. One requires the next-generation sequencing results to look for the presence of high-risk molecular features in such an individual. So we’d not be able to utilize it in this patient.

In many patients with myelofibrosis, we are unable to obtain an accurate karyotype due to the fibrosis that occurs in the marrow. When we are able to obtain a karyotype, many of the prognostic data that have arisen are very consistent with what we have seen with other chronic myeloid disorders, including myelodysplastic syndrome and acute myeloid leukemia. In particular, complex chromosomal changes, meaning multiple abnormalities, deletions of chromosome 5, 7, etcetera, are all adverse, or high risk. It is probably the minority of patients with myelofibrosis who have very adverse chromosomal abnormalities. However, they do tend to accumulate more chromosomal abnormality as they progress toward acute myeloid leukemia. So that issue of clonal progression is reflected in the chromosomal abnormalities.

Prognostic factors tell us how long we might expect an individual myelofibrosis patient to live. Now, many of these criteria from the past were generated based on retrospective data in patients with myelofibrosis that preceded the JAK inhibitor era. We are not quite certain as to the relevance of these prognostic features and how they relate to our current medical therapies and outcomes.

It is not clear that there is a specific chromosomal change linked with the outcomes associated with JAK inhibitor therapy at this time. That may evolve in the future, but at the current time, it is not a major component of our processes. I view that these prognostic scores are the most beneficial in helping us estimate survival and make decisions as they relate to the timing of stem cell transplantation.

Transcript edited for clarity.

Case: 72-Year-Old Man Diagnosed With Primary Myelofibrosis

December 2018

  • A 72-year old man presents to primary care physician with complaints of fatigue, headache, night sweats, poor appetite, and 10-15lb weight loss over past few months; report of increased abdominal pain over the last 3 months
  • PMH: mild hypertension
  • PE: BP 130/85; Splenomegaly ~14 cm below left costal margin
  • Lab values:
    • HGB: 8.9 g/dL
    • Platelets: 189 x 109/L
    • WBC: 27.2 x 109/L
    • Serum LDH: 1500 U/L
    • Serum EPO: 11.5 mU/mL
  • Bone Marrow Biopsy:
    • MF-2
    • Circulating blasts, 1.2%
    • JAK-V617F mutation, del(20q)
  • Diagnosis: Primary myelofibrosis