A 68-year-old male patient recently visited my hospital complaining of fatigue, weight loss, and abdominal distension. On examination, the spleen was significantly enlarged, and blood tests revealed anemia, thrombocytopenia, and elevated LDH levels.

Bone marrow biopsy revealed grade 3 fibrosis, along with numerous atypical megakaryocytes, and JAK2 mutation positivity, leading to a suspicion of primary myelofibrosis (PMF).

Primary myelofibrosis (PMF) is a rare blood disorder characterized by progressive fibrosis in the bone marrow, resulting in a gradual decline in the ability to produce blood cells. When the bone marrow's function of producing red blood cells, white blood cells, and platelets is impaired, these cells are not produced in sufficient quantities.

As a result, symptoms such as anemia, bleeding tendencies, increased risk of infection, and abnormal enlargement of the spleen and liver may occur, leading to abdominal discomfort and weight loss. The proliferation of malignant hematopoietic cells caused by mutations in genes, such as JAK2, CALR, and MPL, plays a central role in the pathophysiology of the disease.

Complex diagnostic process

PMF is difficult to diagnose with a simple blood test. The presence of “teardrop cells” (teardrop-shaped red blood cells) in a peripheral blood smear or evidence of fibrosis in a bone marrow biopsy is a key diagnostic clue.

Additionally, genetic testing for mutations in genes such as JAK2, CALR, and MPL, as well as chromosomal abnormalities and cytogenetic analysis, is necessary for a definitive diagnosis. Recently, next-generation sequencing (NGS) technology has been introduced and is being used for prognosis prediction.

The abovementioned patient was classified as “intermediate-risk group 2” based on the DIPSS-plus prognosis prediction tool, and a personalized approach was planned accordingly.

Treatment strategy: a balance between drug therapy and transplantation

The treatment of PMF varies, depending on the patient's prognosis group. In many cases, low-risk patients require only observation without active treatment. However, patients in the intermediate-risk group or higher require treatment to control symptoms and prolong survival.

This patient was started on ruxolitinib, a JAK inhibitor, and showed a good response with a 35 percent or greater reduction in spleen size after one year. However, allogeneic hematopoietic stem cell transplantation may be necessary for a complete cure of the disease, and we are currently securing a donor and discussing the timing of transplantation.

Importance of prognosis measurement

PMF is a disease characterized by significant differences in prognosis among patients. As a result, various prognostic prediction tools, such as IPSS, DIPSS, DIPSS-plus, MIPSS70+ v2.0, and GIPSS, have been developed. Precise evaluation systems reflecting genetic mutations and chromosomal abnormalities are actively utilized in clinical practice.

For patients considering transplantation, the Myelofibrosis Transplant Scoring System (MTSS) can predict post-transplantation survival rates. The average survival rate after transplantation is reported to be around 50 percent, with variations depending on the MTSS risk group.

Treatment prospects for the future

While treatment options were limited in the past, the availability of JAK inhibitors has expanded, and new drugs with novel mechanisms are being developed, raising hopes for improved quality of life and survival rates for people with PMF.

Currently, the drugs covered by insurance in Korea are ruxolitinib and fedratinib, and momelotinib, which has advantages in terms of anemia, is expected to be covered by insurance soon.

Besides, various agents with different mechanisms of action, including antifibrotic and bone marrow fibrosis inhibitors, BCL-2 inhibitors, such as navitoclax, histone deacetylase inhibitors (HDAC inhibitors), BET protein inhibitors (chromatin regulatory factors), and TGF-β pathway inhibitors, are currently in clinical trials.

Primary myelofibrosis (PMF) remains a challenging disease. However, with early diagnosis, precise prediction-based treatment strategies, and advancements in drug and transplantation technologies, improved treatment outcomes are anticipated. Additionally, with accurate prognosis assessment tailored to the patient's condition and personalized treatment approaches, PMF could become a manageable disease.