Patient Profile: A 68-Year-Old Woman with Myelofibrosis

Video

Abdulraheem Yacoub, MD, presents the case of a 68-year-old woman with myelofibrosis and offers his initial impressions.

Case: A 68-Year-Old Woman with Myelofibrosis

  • A 68-year-old woman presented to her physician with symptoms of mild fatigue, moderate night sweats, and abdominal pain/fullness lasting 4 months; she also reported increased bruising and unexplained weight loss
  • Spleen was palpable 8 cm below the left costal margin
  • Genetic testing shows a JAK2 V617F mutation; CALR negative; Karyotype: 46XX
  • Bone marrow biopsy: megakaryocyte proliferation and atypia with evidence of reticulin fibrosis
  • Blood smear reveals leukoerythroblastosis
  • Diagnosis: Primary myelofibrosis
  • Risk: DIPSS: Intermediate-2; MIPSS70: Intermediate risk
  • Labs demonstrate:
    • RBC 3.40 x 1012/L
    • HGB 13.2 g/dL
    • HCT 36%
    • MCV 94 fL
    • WBC 23.0 x 109/L
    • PLT 450 x 109/L
    • PB Blasts 1%

Transcript:

Abdulraheem Yacoub, MD: Hello, my name is Abdulraheem Yacoub. I’m an associate professor at the University of Kansas Cancer Center. It‘s my pleasure to work with Targeted Oncology™ to present this program to our colleagues and our oncologists regarding a Case-Based Peer Perspectives for a 68 year-old woman with myelofibrosis.

We’re going to discuss a patient who presents with a new diagnosis of myelofibrosis. She presents to her physician with symptoms of fatigue, moderate night sweats, abdominal pain, and fullness, which have been going on for the last 4 months. She also reports increased bruising and unexplained weight loss. Upon examination, the patient had an enlarged spleen that was palpable 8 cm below the left costal margin. She underwent the appropriate work-up, which included genetic testing that identified a JAK2 V617F mutation. The additional testing for mutation was negative for CALR and MPL mutations. She had cytogenetics that showed a normal female karyotype, and she underwent a bone marrow biopsy that was abnormal for megakaryocytic proliferation with atypia, as well as increased fibrosis with a grade of 2 to 3 of 3.

On her peripheral blood testing, the patient had leukoerythroblastosis with immature white cell forms circulating in the blood. This resulted in a diagnosis of primary myelofibrosis. Additional laboratory testing identified a hemoglobin level of 13.1 g/dL, a platelet count of 450 per mm3, a white blood cell count of 23,000 per mm3, and peripheral blood blast percentage of 1%. Subsequently, this resulted in a confirmed diagnosis of primary myelofibrosis as well as a Dynamic International Prognostic Score identifying a relatively high risk myelofibrosis with intermediate-2 myelofibrosis and a MIPS70 [Mutation-enhanced International Prognostic Scoring System 70] score of intermediate-risk [disease].

Myelofibrosis is a rare blood cancer. The diagnosis of a new case of myelofibrosis requires high index of suspicion, as well as the collection of major and minor criteria. The WHO [World Health Organization] criteria for myelofibrosis have been revisited and edited, and I always recommend that we seek the current version for diagnosis. The diagnosis requires a bone marrow biopsy. This is essential to make the original diagnosis and for prognostic purposes. The morphology of myelofibrosis requires the presence of megakaryocytes with atypia, a cornerstone of this diagnosis, as well as the demonstration of reticular fibrosis with a grade of 2 or 3 of 3. If patients do not meet those criteria, they could meet the criteria of other myeloproliferative neoplasms, including nonfibrotic myelofibrosis.

As patients meet the major criteria of a comparable bone marrow morphology, the other major criteria include administration of clonal marker or driver mutation, such as JAK2 mutation, because this patient did test positive for that. There are other driver mutations that can lead to the same diagnosis in the absence of the 3 common driver mutations and evidence of clonality on an extended panel NGS [next-generation sequencing] are required to prove that this is a neoplastic myelofibrosis and to identify this from other nonmalignant causes of myelofibrosis, such as immune disorders. Another major criterion is to exclude other hematologic disorders, such as CML [chronic myeloid leukemia], PV [polycythemia vera], or ET [essential thrombocytopenia], which isn’t challenging if you’ve completed a bone marrow biopsy with karyotyping.

Patients need to meet all these major criteria to make a diagnosis. In addition, they need to meet at least 1 minor criterion. Our patient meets a few of these criteria: the presence of B symptoms, which are defined as having consistent fevers, a weight loss of over 10%, or the presence of drenching night sweats at least 2 nights a week for at least 1 month. Our patient has at least 2 of those B symptoms, so this is compatible with her diagnosis. In addition, a minor criterion is leukoerythroblastosis, which is the presence of immature white blood cells forming in the blood, including blasts. [Other symptoms include] anemia, thrombocytopenia, elevated LDH [lactate dehydrogenase], and an enlarged spleen, which this patient also has. This patient meets all major criteria and multiple minor criteria.

I absolutely recommend that we adhere to these criteria because many diseases look like myelofibrosis, and other cancers have some of the features of myelofibrosis. To make a clear distinction of this diagnosis, we need to adhere strictly to the WHO criteria for myelofibrosis. This patient has a classic presentation, and she is at the expected age for myelofibrosis. She presents with progressive symptoms of enlarging spleen and B symptoms that are compatible with such a diagnosis. She’s fortunate that she continues to have preserved blood counts—her hemoglobin and platelet counts have been preserved—which opens a lot of therapeutic options for her with little restrictions.

Transcript edited for clarity.

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