JAK Inhibition for the Management of Primary Myelofibrosis - Episode 1

Criteria Used in the Diagnosis of Myelofibrosis

Rami S. Komrokji, MD:The case is a classical presentation for patients with myelofibrosis. This is a 66-year-old gentleman who presented with fatigue, was found to have splenomegaly, and the laboratory test showed anemia, leukocytosis, and elevated LDH [lactate dehydrogenase]. On his physical exam, he obviously had splenomegaly.

So this is a classical presentation for patients with myelofibrosis. Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm characterized by the presence of constitutional symptoms, splenomegaly, cytopenias. It’s one of the most symptomatic myeloproliferative diseases. The median age is usually 68, 70. So this really represents a classical presentation. Although symptoms are not specific for the disease, when we put all of the information together, that really gears toward myelofibrosis.

For the myelofibrosis diagnosis, one needs to establish certain criteria: The bone marrow findings, including the presence of fibrosis. Fibrosis is not exclusive for myelofibrosis. It can be seen as reactive and in other hematologic malignancies. There are stages of myelofibrosis where fibrosis can’t be seen. We call that prefibrotic myelofibrosis.

But presence of megakaryocytic atypia, granulocytic hyperplasia, and fibrosis obviously are criteria required for the diagnosis. One has to exclude other hematological diseases—namely CML [chronic myeloid leukemia]—checking forBCR-ABL, and then establish some evidence of clonality by one of the phenotypic driver markers in myelofibrosis such as theJAK2mutation. There are minor criteria we look at such as anemia, leukocytosis, presence of splenomegaly, and elevated LDH.

So this patient had fibrosis in the bone marrow. He had aJAK2mutation. He’s anemic, has leukocytosis, splenomegaly, an elevated LDH, and there is no evidence of other hematological disease. So he meets all of the criteria for myelofibrosis.

Sometimes establishing the diagnosis may not be as straightforward. The fibrosis can be reactive. We have seen cases with lymphomas, hairy cell leukemia, and connective tissue disease where patients present with fibrosis. Sometimes, as I mentioned, there is an early stage of myelofibrosis called prefibrotic myelofibrosis where there’s less than grade 2 fibrosis on the bone marrow. Sometimes that may be missed or diagnosed as essential thrombocythemia or another type of myeloproliferative disease.

Transcript edited for clarity.

Case: 66-Year-Old Man Diagnosed With Primary Myelofibrosis

January 2019

  • A 66-year old man presents to primary care physician with complaints of fatigue, headache, and abdominal discomfort when taking deep breaths
  • PMH: depression
  • PE: Splenomegaly ~7 cm below left costal margin
  • Lab values:
    • HGB: 9.2 g/dL
    • Platelets: 242 x 109/L
    • WBC: 26.2 x 109/L
    • Serum LDH: 1400 U/L
    • Serum EPO: 10.9 mU/mL
  • Bone Marrow Biopsy:
    • MF-3
    • Circulating blasts, 1.1%
    • JAK V617Fmutation; trisomy 8
  • Peripheral Blood Smear: leukoerythroblastosis
  • Diagnosis: Primary myelofibrosis