Approach to myeloproliferative neoplasms: Clinical sciences

Myeloproliferative neoplasms are a group of neoplastic conditions characterized by the proliferation of bone marrow cells from the myeloid lineage. These include red blood cells and platelets, as well as granulocytes, which include neutrophils, eosinophils, basophils, and monocytes.

The expanded cell lines are morphologically normal, meaning there’s no dysplasia, which distinguishes these conditions from myelodysplastic ones. The four classic myeloproliferative neoplasms include chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and primary myelofibrosis.

Now, if your patient presents with a chief concern suggesting a myeloproliferative neoplasm, first, perform an ABCDE assessment to determine if they are unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, don’t forget to provide supplemental oxygen!

Now, here’s a clinical pearl! Patients with myeloproliferative neoplasms may present as unstable due to several different reasons. The first one is thrombosis. In fact, some individuals have an increased risk of acquired hypercoagulability, which can result in life-threatening thrombotic events, such as myocardial infarction or pulmonary embolism! Next, there’s hemorrhage, which can occur due to platelet dysfunction and result in intracranial or gastrointestinal bleeding. Finally, some individuals can develop acute myeloid leukemia and present with tumor lysis syndrome or acute disseminated intravascular coagulation.

Alright, now that we’ve addressed unstable patients, let’s go back to the ABCDE assessment and discuss stable ones. If your patient is stable, perform a focused history and physical examination and order labs, including a complete blood count with differential and a peripheral smear. Your patient will typically report a history of non-specific systemic symptoms like fatigue, night sweats, fever, and weight loss.

Next, they might report a history of thrombosis or bleeding, while their physical exam often reveals splenomegaly. Complete blood cell count will reveal cytosis, or in other words, erythrocytosis, thrombocytosis, leukocytosis, or a combination of these. Additionally, the peripheral smear will reveal the elevation of one or more myeloid-lineage cells with no dysplasia!

With these findings, you should consider reactive or secondary cytosis and assess your patient for potential causes! For example, infections are typically associated with leukocytosis, while anemia and acute inflammation are often characterized by thrombocytosis. Finally, chronic hypoxia in patients with cardiopulmonary conditions can result in erythrocytosis. If you identify a secondary cause of cytosis, you are dealing with reactive or secondary cytosis and not a primary problem of the bone marrow.

On the other hand, if you identify no secondary causes, this is highly suggestive of myeloproliferative neoplasms. Next, check for the presence of the Philadelphia chromosome by ordering BCR-ABL1 genetic testing. The Philadelphia chromosome occurs as a result of a translocation that involves the BCR gene in chromosome 22 and the ABL1 gene in chromosome 9, which results in the formation of the BCR-ABL1 gene. This gene encodes the continuously active tyrosine kinase that stimulates unregulated myeloid cell division and proliferation.

If the BCR-ABL1 testing is positive, this means that your patient has a Philadelphia chromosome, so you can diagnose the PH-positive myeloproliferative neoplasm, more specifically chronic myeloid leukemia. Next, obtain a bone marrow biopsy, which will reveal hypercellularity with proliferation of granulocyte lineage, as well as blasts and, in some cases, fibrosis.

Finally, don’t forget to assess the phase of chronic myeloid leukemia by reviewing peripheral blood and bone marrow findings! If the peripheral smear reveals less than 20% of basophils, and the bone marrow reveals less than 10% of blasts, diagnose the chronic phase of chronic myeloid leukemia. Chronic phase CML is relatively indolent and easily controlled with oral medications, but keep in mind these patients might progress to a more advanced phase, so they need to be monitored.

Next, if the peripheral smear reveals at least 20% of basophils or bone marrow with 10-19% of blasts, diagnose the accelerated phase. Finally, if peripheral smear or bone marrow shows 20% of blasts, diagnose the blast phase. The accelerated phase and the blast phase both represent advanced disease, a more aggressive process that resembles acute leukemia.

Now, let’s go back to BCR-ABL1 testing and take a look at BCR-ABL1-negative individuals. In this case, there’s no Philadelphia chromosome, so you can diagnose Philadelphia-negative myeloproliferative neoplasms. Next, order additional genetic testing and check for JAK2, CALR, and MPL mutations, which can also result in uncontrolled myeloid cell division and proliferation. Finally, don’t forget to obtain a bone marrow biopsy.