Incidence, Survival and Prevalence Statistics of Classical Myeloproliferative Neoplasm in Korea

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more of the myeloid lineage cells. With recent expansion of understanding, there has been reclassification of the disease category since the first description of the concept of ‘myeloproliferative disorders (MPD)’ in the 1950s (1). A most recent revision of the classification of the diseases in this category has been issued by the World Health Organization (WHO) in 2008 (2) to include chronic myelogenous leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (MF), essential thrombocythemia (ET), chronic eosinophilic leukemia, mastocytosis and other unclassifiable MPNs. Of the diseases in the MPN category, the classical Philadelphia chromosome-negative MPNs include PV, MF and ET. Reported worldwide incidence of the classical MPNs combined is approximately 0.5-6/100,000, annually, with peak incidence at the 5th to 7th decades of life (3, 4, 5, 6, 7, 8). However, there have been more recent changes especially regarding accuracy and frequency of the diagnosis of the classical Philadelphia chromosome-negative MPN, owing to the discovery and clinical utilization of mutations in Janus kinase 2 (JAK2) (9) and Calreticulin (CALR)(10, 11).

The Korean data for the hematologic malignancies (12) and the myeloid malignancies (13) have been previously published. During 1999 to 2012, myeloid malignancies took 1.7% of all cancer incidences, and MPNs took 33.8% of the myeloid malignancies. But the incidence and survival for each of disease of the MPN among Korean patients have not been reported.

The Ministry of Health and Welfare, Korea, initiated a nationwide hospital-based cancer registry called the Korea Central Cancer Registry (KCCR) as early as 1980. The registry collected 80%–90% of cancer cases annually from more than 180 training hospitals throughout the country. In 1999, the KCCR expanded cancer registration to cover the entire population under the Population-Based Regional Cancer Registry program. Details of the history, objectives and activities of the KCCR have been documented (14). Official registration of MPN at KCCR, employing the International Classification of Diseases for Oncology 3rd edition (ICD-O-3) (15) began in 2003. The Health Insurance Review and Assessment Service (HIRA) of Korea collects the claims data of the National Health Insurance, and offers clinical information including diagnosis, treatment, and prescription data for clinical research. The claims data covered approximately 46 million patients per year which is approximately 90% of the total population in Korea and included claims from almost 80,000 healthcare service providers, as of year 2011 (16).

The objectives of this report are to estimate and report the nationwide statistics of the classical MPN including PV, MF and ET from 2003 to 2011, using the Korea National Cancer Incidence Data Base (KNCIDB) and HIRA data.

This is the first study to have presented the epidemiological data of classical, Philadelphia-chromosome negative MPN in Korean patients, utilizing comprehensive data from the KNCIDB and the HIRA.

The incidence of all PV, MF, and ET constantly increased during the years observed, with the most recent crude annual incidence of PV, MF, and ET being 0.40, 0.15, and 0.84 per 100,000, respectively. The prevalence rates have also increased over the years, most recent crude rates being 4.53, 2.60, and 7.10 per 100,000 for each PV, MF, and ET, by the HIRA data.

Classical MPNs are rare diseases, but as the disease courses are generally long and as the diseases can cause debilitating symptoms and complications, the optimal diagnosis and management is important in enhancing public health. Current guidelines for diagnosis follow the suggestion published by WHO (18) and use blood cell counts, bone marrow results and JAK2 V617F mutation results for diagnosis. More recently, CALR mutation was discovered in JAK2 negative MF and ET patients (10, 11), assisting more accurate diagnosis of MPN. Treatment options include low dose aspirin, phlebotomy, and cytoreductive therapy with hydroxyurea, anagrelide, and interferon-α for PV and ET. The classical therapy for MF was bone marrow transplantation. Recently drugs targeting JAK2mutation has shown very promising results for classical MPN (19, 20).

The epidemiological data of classical MPN reported in other countries were generally in similar range with our data, although variable. A US epidemiological study using the North American Association of Central Cancer Registries (NAACCR) and the Surveillance, Epidemiology, and End Results (SEER) Program data reported incidence rates of PV, MF, and ET at 0.79, 0.25, and 0.53 per 100,000 (7). HAEMACARE, a European cancer registry-based project to improve the standardization and availability of population-based data on hematologic malignancies, reported crude incidence rate of MPN excluding chronic myeloid leukemia, at 2.24 per 100,000 (8). A meta-analysis of incidence and prevalence data for classical MPNs published in 2014, suggested the combined annual incidence rates for PV, MF, and ET as 0.84, 0.47, and 1.03 per 100,000, respectively (6). The meta-analysis report included extensive data of which publication dates ranged from 1946 to 2012. Geographically, the study was intended to include all studies without geographical limits and included one Japanese study, but was analyzed using mostly the US and European data. But even considering the racial and geographical difference, the pooled data showed high heterogeneity, showing heterogeneity in data even from similar geographic regions.

The heterogeneity of data between reports and the constant increasing pattern of incidence/prevalence of our data may be owing to a number of factors. The most important cause is the still growing understanding of the disease, and the development of diagnostic tools and disease classifications, accordingly. WHO classification and diagnostic guidelines for MPN has been re-issued in year 2008, and the discovery of JAK2mutation has led to increased recognition of diseases in the MPN category and to more accurate diagnosis. The discovery of CALR mutation may even lead to further increase in the number of MPN diagnosis in the future. Another attributable factor is that the systemic registrations of the disease category have only recently begun in many countries. MPN have been officially registered in Korea cancer registry since 2003, and since 2001 in the USA. Other additional factors may include the increase in average life span and improved access to healthcare over the years.

This study is the first to present the Korean nationwide epidemiological data of each disease in the classical MPN category. The statistics are important information for clinicians, researchers as well as administrators, on understanding epidemiological characteristics and establishing future strategies on managing MPNs in Korea. The statistics can be utilized to compare the Korean status to international data and guidelines. Continued systemic registration and periodic report is warranted, to improve the accuracy of the data in association with the improvement in the diagnostic accuracy.