Myeloproliferative neoplasm overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]

Overview

The myeloproliferative neoplasm are a group of eight disease subtypes of the bone marrow in which excess cells are produced. Myeloproliferative neoplasm may be classified according to the World Health Organization into eight subtypes (chronic myelogenous leukemia, BCR-ABL1–positive, chronic neutrophilic leukemia, polycythemia vera, primary myelofibrosis, essential thrombocythemia, chronic eosinophilic leukemia, not otherwise specified, mastocytosis, myeloproliferative neoplasms, unclassifiable). They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. Clinical and pathologic features in the myeloproliferative neoplasms are due to dysregulated proliferation and expansion of myeloid progenitors in the bone marrow, resulting in altered populations of granulocytes, erythrocytes, or platelets in the peripheral blood. Myeloproliferative neoplasm is caused by a mutation in the BCR-ABL, Janus kinase 2, and calreticulin genes. Patients may be asymptomatic at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include fever, fatigue, and bleeding. The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, aspirin, and palliative care.

Historical Perspective

The first description of myeloproliferative neoplasm dates back to the late 19th century, when Sir Louis Vasquez studied a patient with excess red blood cells. Myeloproliferative neoplasm was first brought to attention as an important clinical entity by Dr. William Dameshek, an American hematologist, in 1951. In 2005, the link between the JAK2 mutation and polycythemia vera was discovered. The World Health Organization created diagnostic criteria for myeloproliferative neoplasms in 2008, and this was revised in 2016.

Classification

Myeloproliferative neoplasm may be classified according to the World Health Organization into eight subtypes: polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myelogenous leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, myeloproliferative neoplasms unclassifiable, and mastocytosis. Each subtypes is based on a distinct malignant cell, and each subtype has different criteria for diagnosis.

Pathophysiology

The pathophysiology of myeloproliferative neoplasms is based on the specific subtype of myeloproliferative neoplasm. Each of the 8 different myeloproliferative neoplasms have a slightly different pathophysiologic basis. Primary cytogenetic abnormalities have not been identified in the majority of myeloproliferative neoplasms. Aberrant activation of tyrosine kinases and associated signaling pathways is frequently implicated as the disease-initiating event for many of the myeloproliferative neoplasms. Clinical and pathologic features in the myeloproliferative neoplasms are due to dysregulated proliferation and expansion of myeloid progenitors in the bone marrow, resulting in altered populations of granulocytes, erythrocytes, or platelets in the peripheral blood.

Causes

Myeloproliferative neoplasm is caused by mutations in various genes. Different gene mutations are responsible for each of the 8 subtypes of myeloproliferative neoplasms. Importantly, multiple different gene mutations can cause a single disease.

Differentiating Myeloproliferative Neoplasm from other Diseases

Myeloproliferative neoplasm must be differentiated from myelodysplastic syndrome, acute myelogenous leukemia, [[acute lymphoblastic leukemia, Waldenstrom's macroglobulinemia, and lymphoproliferative disorder. Each of these conditions has unique set of causes, laboratory abnormalities, physical exam findings, and therapies.

Epidemiology and Demographics

The incidence of myeloproliferative neoplasm is approximately 7.8 per 100,000 individuals worldwide. The different subtypes of myeloproliferative neoplasm have different incidence and prevalence statistics. Males are more commonly affected than females, and older persons are more commonly affected than younger persons.

Risk factors

There are four major categories of risk factors for myeloproliferative neoplasm. Genetic mutational events comprise the most common risk factor. Other risk factors include advanced age, prior cytotoxic chemotherapy, and autoimmune disease.

Screening

There are currently no guidelines for screening for myeloproliferative neoplasm. Monitoring of the complete blood count is done routinely.

Natural History, Complications and Prognosis

The natural history of myeloproliferative neoplasm begins with weight loss, fever, and night sweats. The natural history depends on the subtype of myeloproliferative neoplasm. Common complications of myeloproliferative neoplasm include splenomegaly, bleeding, thrombosis, bone marrow fibrosis, and acute leukemia. Prognosis depends on the subtype of myeloproliferative neoplasm. Each subtype has its own prognostic scoring system. In general, patients with polycythemia vera, essential thrombocythemia, and chronic myeloid leukemia have better prognosis than patients with primary myelofibrosis. The prognosis is generally good with treatment.

Diagnosis

History and Symptoms

Patients may be asymptomatic at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include fever, fatigue, and bleeding.

Physical Examination

Patients with myeloproliferative neoplasm are usually well-appearing. Physical examination of patients with chronic myelogenous leukemia is usually remarkable for skin bruising, fever, splenomegaly, and lymphadenopathy.

Laboratory Findings

Patients with myeloproliferative neoplasm are usually well-appearing. Physical examination of patients with chronic myelogenous leukemia is usually remarkable for skin bruising, fever, splenomegaly, and lymphadenopathy.

Chest X-Ray

Chest x-ray may be helpful in the diagnosis of myeloproliferative neoplasm and can reveal pleural effusions, pneumonia, and pulmonary edema.

CT

Abdominal and chest CT scan may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on CT scan suggestive of myeloproliferative neoplasm include enlarged lymph nodes, hepatosplenomegaly, splanchnic venous thrombosis, and pulmonary embolism.

MRI

Brain MRI is helpful in the detection of thrombotic events, such as ischemic stroke, in patients with myeloproliferative neoplasm. Abdominal MRI is helpful in the detection of mesenteric thrombosis in patients with myeloproliferative neoplasm.

Ultrasound

Ultrasound may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on abdominal ultrasound suggestive of myeloproliferative neoplasm include enlarged lymph nodes, hepatosplenomegaly, and ascites. Findings on extremity ultrasound include thrombosis.

Other Imaging Findings

Other imaging studies for myeloproliferative neoplasm include positron emission tomography (PET) scan, which helps to detect metastasis in bone marrow and to follow up medical treatment.

Other Diagnostic Studies

Other diagnostic studies for myeloproliferative neoplasm include bone marrow aspiration and trephine biopsy, erythropoietin level, lumbar puncture, and lymph node biopsy.

Treatment

Medical Therapy

Medical therapy for myeloproliferative neoplasm is based on the specific subtype of myeloproliferative neoplasm. The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, cytoreduction, aspirin, and palliative care. Treatment is directed at reducing the excessive numbers of blood cells.

Surgery

Surgical intervention is usually not recommended for the management of chronic myelogenous leukemia, unless there is splenomegaly.

Primary Prevention

There is no established method for primary prevention of myeloproliferative neoplasm.

Secondary Prevention

Secondary prevention measures include routine monitoring of laboratory values, including complete blood count (CBC) and metabolic panel.

Future of Investigational Therapies

Future or investigational therapies in myeloproliferative neoplasms include BLU-285, JQ1, and suberoyl anilide hydroxamic acid. Each of these investigational agents carries a unique mechanism of action on myeloid cells. The agents are currently in clinical trials.