Dr. Ayesha Warsi

Number four, LDH increased above the upper limit of normal.

And number five, leukoerythroblastic picture in peripheral blood spread.

Treatments of myelofibrosis is directed by a hematologist and is largely guided by risk stratification as well as assessment of symptom burden.

Various prognostic models, like the Mutation-Enhanced International Prognostic Score System, also known as MIPSS,

incorporate clinical and laboratory features as well as cytogenetics and molecular testing results to estimate survival and risk of disease progression.

Some features that classify a patient as high risk include certain abnormalities on cytogenetic testing, lower baseline hemoglobin, circulating blasts, constitutional symptoms, and the absence of a CalR mutation.

High-risk primary myelofibrosis is associated with a lower median overall survival.

Thus, high-risk patients should be assessed for stem cell transplant eligibility, which will factor in age, medical comorbidities, and donor availability.

Transplant eligible patients with high risk primary myelofibrosis are recommended for allogenic stem cell transplant, which is the only potentially curative treatment option.

Patients with low risk disease and patients with high risk disease who are not eligible for a stem cell transplant are managed with symptom based therapies.

Anemia may be managed with red blood cell transfusions or erythropoiesis-stimulating agents like EPO.

Androgens like danosol or immunomodulating agents like lenalidomide may be used for anemia management in select patients.

First-line management of constitutional symptoms and or splenomegaly are JAK2 inhibitors, such as ruxolitinib.

Important side effects of JAK2 inhibitors to be aware of include drug-induced anemia and thrombocytopenia.

Hydroxyurea can also be used for patients experiencing splenomegaly or other symptoms related to thrombocytosis and leukocytosis in the absence of anemia, who are also not eligible for stem cell transplant or JAK2 inhibitors.

Splenectomy may also be considered to manage symptoms related to splenomegaly.

However, it is associated with increased morbidity and mortality and usually reserved for select patients.

For burdensome sites of extramedullary hematopoiesis, consultation with radiation oncology for consideration of radiation may also be required.

Finally, in some low-risk or asymptomatic patients, a watch and wait strategy with regular clinical observations may be appropriate.

Finally, all myeloproliferative neoplasms, including myelofibrosis, carry a risk of progression to a more advanced phase of disease known as accelerated and blast phase disease.