Diagnostic and therapeutic guideline for myeloproliferative neoplasm

Soo-Mee Bang; Ho Young Kim; Hyo Jung Kim; Hee-Jin Kim; Jong Ho Won; Bong Seog Kim; Chul-Won Jung; Hyun-Sook Chi

doi:10.5124/jkma.2011.54.1.112

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Bang, Kim, Kim, Kim, Won, Kim, Jung, Chi, and Korean Myeloproliferative Neoplasm Working Party: Diagnostic and therapeutic guideline for myeloproliferative neoplasm

Original Article

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2011; 54(1): 112-126.

Published online: 15 January 2011

DOI: https://doi.org/10.5124/jkma.2011.54.1.112

Diagnostic and therapeutic guideline for myeloproliferative neoplasm

Soo-Mee Bang, MD^1,^*, Ho Young Kim, MD^2,^*, Hyo Jung Kim, MD², Hee-Jin Kim, MD³, Jong Ho Won, MD⁴, Bong Seog Kim, MD⁵, Chul-Won Jung, MD⁶, Hyun-Sook Chi, MD⁷; Korean Myeloproliferative Neoplasm Working Party

¹Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

²Department of Internal Medicine, Hallym University Medical Center, Anyang, Seoul, Korea.

³Department of Laboratory Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.

⁴Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.

⁵Department of Internal Medicine, Seoul Veterans Hospital, Seoul, Korea.

⁶Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.

⁷Department of Laboratory Medicine, University of Ulsan College of Medicine, Seoul, Korea.

Corresponding author: Hyun-Sook Chi, hschi@amc.seoul.kr

Equal contributor:

*These two authors contributed equally to this article.

Received 20 May 2010 Accepted 24 September 2010

(open-access):

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The myeloproliferative neoplasm (MPN), polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) are clonal hematopoietic stem cell diseases that share in common overproduction of one or more of the formed elements of the blood with overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Therefore, accuracy of diagnosis is the cornerstone of therapy. The World Health Organization diagnostic criteria for both the classic BCR-ABL-negative MPNs (that is PV, ET, and PMF) and chronic eosinophilic leukemia/hypereosinophilic syndrome have been revised in the 2008 edition, by incorporating new information on their V617F mutation in the Janus kinase 2 (JAK2) tyrosine kinase. The JAK2 V617F point mutation makes the normal hematopoietic progenitor cells hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells, leading to trilinear hematopoietic myeloproliferation. JAK2 V617F is found in most patients with PV, ET, or PMF and is, therefore, useful as a clonal marker when present. However their absence does not exclude the diagnosis of an MPN. The major complications of the MPN are thrombosis, hemorrhage and extramedullary hematopoiesis with massive splenomegaly and bone marrow failure. Myelofibrosis is classically listed as a complication of the MPN. Current treatment options are low dose aspirin, phlebotomy and cytoreductive therapy with hydroxyurea, anagrelide, and interferon for PV and ET but the most effective therapy is still bone marrow transplantation for PMF for the relief of symptoms and the prevention of complications. Drugs targeting JAK2 V617F are promising. This article reviews the changes in diagnostic criteria and algorithms, and also provides treatment guidelines that are tailored to routine clinical practice.

Keywords: Myeloproliferative neoplasm, Janus kinase 2 V617F, World Health Organization criteria

Figures and Tables

Figure 1

(A) Annual registered number of patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). (B) Assumptive prevalence rate of PV, ET, and PMF per 100,000 persons per one year (from the databases of Korean Health Insurance Review and Assessment Service).

Figure 2

Correlation between vascular events (VE) and mutational levels of Janus kinase 2 V617F.

Figure 3

Therapeutic recommendation for patients with polycythemia vera (PV).

Figure 4

Therapeutic recommendation for patients with essential thrombocythemia (ET).

Table 1

The 2008 World Health Organization (WHO) diagnostic criteria for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) [9]

Hgb, hemoglobin; Hct, hematocrit; CML, chronic myelogenous leukemia; MDS, myelodysplastic syndrome; BM, bone marrow; Epo, erythropoietin; EEC, endogenous erythroid colony; LDH, lactate dehydrogenase.

^a)Diagnosis of polycythemia vera (PV) requires meeting either both major criteria and one minor criterion or the first major criterion and 2 minor criteria. Diagnosis of ET requires meeting all four major criteria.

^b)Small to large megakaryocytes with an aberrant nuclear/cytoplasmic ratio and hyperchromatic and irregularly folded nuclei and dense clustering.

Table 2

Category of risk in polycythemia vera (PV)

Table 3

Risk stratification in essential thrombocythemia

^a)Not yet established.

Table 4

Definitions of refractoriness or intolerance to hydroxyurea (HU)

WBC, white blood cell; Hb, hemoglobin.

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