Idea Transcript
Myeloproliferative Disease Updated: Feb 26, 2016 Author: Haleem J Rasool, MD, FACP; Chief Editor: Emmanuel C Besa, MD more...
OVERVIEW
Practice Essentials Myeloproliferative diseases are a heterogeneous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. The peripheral smear below shows leukoerythroblastosis and giant platelets in a patient withmyelofibrosis.
Peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows leukoerythroblastosis. This photomicrograph also shows giant platelets.
Patients are at risk for thrombotic and hemorrhagic events. They are also at risk of developing secondary acute leukemia from their underlying disorder, as well as from their treatment.
Signs and symptoms Patients may have a history of the following: Easy fatigability Anorexia, weight loss Abdominal discomfort and early satiety secondary to splenomegaly: Most common in chronic myelogenous leukemia and agnogenic myeloid metaplasia Easy bruising, bleeding, and/or symptoms of thrombosis Swollen, painful joint(s) secondary to gouty arthritis that is secondary to hyperuricemia Priapism, tinnitus, or stupor from leukostasis Left upper quadrant and left shoulder pain as a consequence of splenic infarction and perisplenitis Clinical symptoms can include the following: Pallor (except in patients with polycythemia vera) Plethora secondary to polycythemia Petechiae and/or ecchymosis Palpable spleen and/or liver Occasionally, syndrome of fever accompanied by painful, maculopapular, violaceous lesions on the trunk, arms, legs, and face; this is called acute febrile neutrophilic dermatosis, or Sweet syndrome See Clinical Presentation for more detail.
Diagnosis Laboratory studies The following laboratory studies can be used in the diagnosis of myeloproliferative disease: Complete blood count (CBC) and differential count with microscopic examination of the peripheral smear Leukocyte alkaline phosphatase (LAP) score: To differentiate chronic myelogenous leukemia from other causes of leukocytosis Polymerase chain reaction (PCR) assay or fluorescent in-situ hybridization (FISH) run on peripheral blood: Can detect bcr-abl gene rearrangement; this helps to differentiate chronic myelogenous leukemia from other myeloproliferative diseases Red blood cell mass study: True versus spurious polycythemia Serum uric acid level PCR assay run on bone marrow: To test for JAK2; available for suspected cases of polycythemia vera, essential thrombocythemia, and myelofibrosis Biopsy Bone marrow aspiration and biopsy with cytogenetic studies are required in most, but not all, patients. Cytogenetic studies detect the presence or absence of the Philadelphia chromosome and help to differentiate myeloproliferative disorders from myelodysplastic syndrome. Bone marrow histology shows hypercellularity in most of these disorders. In the case of myelofibrosis, bone marrow fibrosis is demonstrated on the reticulin stain. Bone marrow fibrosis is also detected in the spent phase of chronic myelogenous leukemia and polycythemia vera. See Workup for more detail.
Management Chronic myelogenous leukemia Hematopoietic stem cell transplantation can be considered in young patients with chronic myelogenous leukemia in chronic phase if a human leukocyte antigen (HLA)-matched donor is available. Agents used in the treatment of the disease include the following: Imatinib mesylate (Gleevec): Approved for use in Philadelphia chromosome–positive chronic myelogenous leukemia patients in chronic phase; also indicated for chronic myelogenous leukemia in blast crisis, accelerated phase, or in chronic phase after interferon-alfa therapy failure; this is the treatment of choice for most patients. [1] Interferon alfa: Produces hematologic and molecular remissions in some patients with chronic myelogenous leukemia Low-dose cytosine arabinoside: When added to interferon alfa, has been reported to increase remission rates. Hydroxyurea: For patients with chronic myelogenous leukemia who are intolerant to interferon-alfa therapy Dasatinib (Sprycel): Indicated for the treatment of adult patients with chronic myeloid leukemia in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib. Nilotinib (Tasigna): Indicated for the treatment of chronic-phase and accelerated-phase Philadelphia chromosome-positive chronic myelogenous leukemia in adult patients who are resistant or intolerant to prior therapy including imatinib Polycythemia vera Treatment for this disease is palliative. Young (< 40 y), asymptomatic patients with polycythemia vera can be considered for therapeutic phlebotomies alone to maintain a hematocrit level of less than 45%. Other patients can undergo myelosuppressive therapy with hydroxyurea. Radioactive phosphorous can be used as an alternative therapy in older patients. Essential thrombocythemia No curative treatment is available. The aim of therapy is to maintain the patient’s platelet count within the reference range. This usually can be achieved with hydroxyurea or anagrelide. Myelofibrosis Asymptomatic patients can be monitored clinically until symptomatic. Hydroxyurea is useful to suppress the number of circulating cells. Patients with painful, massively enlarged spleens refractory to myelosuppressive therapy are occasionally treated with radiation therapy, but they may ultimately require splenectomy. In November 2011, a JAK1/JAK2 inhibitor, ruxolitinib (Jakafi), became the first US Food and Drug Administration (FDA)–approved drug for patients with intermediate- or high-risk myelofibrosis. See Treatment and Medication for more detail.