Initial Impression and Presentation of Myelofibrosis

Jamile Shammo, MD:We have a 72-year-old man who presented to his physician with symptoms of fatigue and night sweats, and was found to have splenomegaly on exam that measured about 6 cm below the left costal margin. And his CBC demonstrated a little bit of leukocytosis with a white blood cell count of 22,000, hemoglobin of 9.7, and platelet count was perfectly normal at 255,000. The patient underwent a bone marrow biopsy to evaluate the etiology of the anemia and leukocytosis, and the morphology demonstrated clusters of megakaryocytes and 3+ reticulin fibrosis. There was also molecular testing forJAK2V617F mutation, which turned back positive. At this point, the patient was diagnosed with primary myelofibrosis.

This case demonstrates an older gentleman who is greater than 65 years of age, and here, I’m going to focus the case relative to the International Prognostic Scoring System, which is an important method for us to estimate survival of this patient population. So, it turns out that patients who are over the age of 65 are given a point, essentially, toward that score. The second point is that the hemoglobin of 9.8 represents another point because the presence of anemia seems to also be a negative prognostic indicator in this patient population. And the third is simply the presence of constitutional symptoms. In this situation, it’s night sweats. So, if you added 1 point for each variable, then you have an IPSS score of 3 and this means that this patient has high-risk myelofibrosis. That translates, essentially, to a 2-year survival for this particular patient.

This is not an unusual way for patients with myelofibrosis to present. I have seen a variety of patients who come in with, again, various clinical presentations. This would be 1 possibility. About one-quarter of patients with myelofibrosis may not have any symptoms actually, believe it or not, but then 75% of them will. Other patients may present mainly with very high platelet count, leukocytosis, significant anemia, and some may only present with anemia. I think when you look at the CBC abnormalities in myelofibrosis, it tends to be the most variable of all MPNs. In the beginning, they may end up with cytosis and a little bit of anemia. As the disease goes on, you end up with more manifestations of bone marrow failure and cytopenias.

Transcript edited for clarity.

June 2016

• A 72-year old male presents to his primary care physician with fatigue, abdominal pain lasting 3 months, and night sweats
• PMH includes depression and gout
• Physical Exam: BP, 155/85; spleen palpable 6 cm below costal margin
• Laboratory values:
  • Hb= 9.8 g/L
  • HCT= 38%
  • WBC= 22.3 x10⁹/L
  • Platelets= 255 x10⁹/L
• Bone marrow biopsy:
  • Megakaryocytic proliferation and atypia with evidence of reticulin fibrosis
• Blood smear showed leukoerythroblastosis
• Genetic testing showsJAK2 V617Fmutation
• Diagnosis: Primary myelofibrosis