Diagnosis/Risk Classification for Primary Myelofibrosis

Daniel DeAngelo, MD, PhD:This case involves a 53-year-old woman who presents with early satiety and constitutional symptoms, a blood smear that shows anemia and a low white blood cell count, and thrombocytopenia. Bone marrow examination confirms the diagnosis of primary myelofibrosis, and she has aJAK2V617Fmutation. So, the diagnosis is made. This is a patient with primary myelofibrosis, and unfortunately, this is a young woman who now has symptoms. She needs therapy. And the first thing to determine is, is this patient a stem cell transplant candidate or not? In addition, one can initiate therapy. There’s some missing information here that may be useful in terms of determining prognosis.

First, is a karyotype available? Many patients with chronic myeloproliferative disorders—specifically, primary myelofibrosis—may have a dry aspirate. That is, you’re not going to get a good karyotype. But if one is achieved, it could be very useful in determining stratification in terms of prognosis. Secondly, additional mutations may be important—additional driver mutations or other epigenetic mutations that can deter a poorer overall prognosis.

Regardless of those 2 missing facts, this patient has primary myelofibrosis. I typically use the IWG (International Working Group) criteria for initial diagnosis. This patient would have intermediate-2 disease, given her symptoms and anemia. The other set of criteria that is often used is a DIPSS score, or DIP score, as it’s often referred to. And this patient, again, will have intermediate risk because she is anemic and has constitutional symptoms. She warrants therapy. My initial therapy would be ruxolitinib, as I send her for transplant evaluation in order to assess whether or not a good donor can be found.

One of the biggest complications with myelofibrosis, especially if left untreated, is that patients can develop progressive abdominal distension and, as result of that, abdominal pain and early satiety. Once patients develop early satiety, they develop weight loss. Weight loss is a really profound component of disease progression. In addition to that, patients feel poorly. They often have constitutional symptoms that include fever, night sweats, and sometimes pruritus. And there is something called a total symptom score, or TSS, that Dr Mesa has developed, which can take out the symptoms and put them into a numerical calculation.

As we ask patients questions about how they’re feeling or how are they doing, patients may oftentimes underestimate how poorly they are feeling. And this is an opportunity, with just a very few questions, to quantitate it—objectively calculate how poorly patients are feeling. This can also be used in terms of determining prognosis. The worse a patient is on a total symptom score, the more advanced their disease is, and the more treatment initiation with ruxolitinib—which is the only therapy that we have available to us—is indicated.

Based on their IWG or the DIPSS score, patients are grouped into several classifications: high risk, intermediate 1, intermediate 2, or low risk. It is the intermediate 2-risk and high-risk patients who have a poorer overall prognosis. And what I mean by that is a very limited time of survival. So, these are the patients—specifically, young patients like this case represents—whom you want to think about allogeneic stem cell transplant with. In addition, it’s important to ameliorate some of the symptoms that she’s experiencing. This patient is having abdominal discomfort, early satiety, and now weight loss. If left untreated, she may circle down a pathway that would make her an unsuitable candidate for further therapy.

Transcript edited for clarity.

• A 53-year-old woman complains of increasing abdominal discomfort, early satiety, and 15-lb weight loss over the past 5 months
• Abdominal examination reveals splenomegaly, palpable 8 cm. below the costal margin without hepatomegaly
• CT scans of the chest, abdomen, and pelvis reveal moderate mediastinal lymphadenopathy and splenomegaly
• Laboratory values:
  • WBC: 1.9 x 10³cells/mm³
  • ANC: 1.4 x 10³cells/mm³
  • Hb: 9.1 gm/dl
  • Platelets: 77,000 cells/mm³
• Bone marrow biopsy:
  • MF-3
  • CD34+/CD117+ immunostaining demonstrated 1.2% blasts
  • JAK2-V617Fmutation
• Diagnosis: primary myelofibrosis