Epidemiology of Plasma Cell Leukemia in the Czech Republic

Summary

Background:

Plasma cell leukemia (PCL) is a rare but most aggressive form of monoclonal gammopathies. PCL is characterized by the presence of clonal plasma cells in peripheral blood. There are two forms of PCL – primary which presents de novo in patients with no evidence of previous multiple myeloma and secondary which is a leukemic transformation of relapsed or refractory dis­ease in patients with previously recognized multiple myeloma.

Materials and methods:

This is the first study to provide information on PCL epidemiology in the Czech population us­ing The Czech National Cancer Registry (CNCR) as the basic source of data for the population-based evaluation of PCL epidemiology.

Results:

Accord­ing to CNCR data, there were on average six newly dia­gnosed cases of PCL and four deaths caused by PCL each year in the Czech Republic in the period 2000– 2015. PCL incidence in the Czech Republic was reported at 0.57 per million in 2000– 2015. We suppose that most reported cases of PCL are primary PCL because secondary PCL is a relapse of a previously reported myeloma and, in most cases, is not coded as an independent dia­gnosis in the CNCR.

Conclusion:

Data from registries such as the CNCR can provide useful information on epidemiology of various dis­eases. These data, however, have several limitations, such as dia­gnostic criteria and proper cod­ing of not only the dis­ease itself, but also its various forms. These limitations have to be taken into account dur­ing the process of results interpretation.

Key words

plasma cell leukemia –  epidemiology –  Czech National Cancer Registry (CNCR) –  Czech Republic

Introduction

The importance of cancer epidemiology has been grow­ing steadily, partly due to the grow­ing cancer burden worldwide. The Czech Republic is no exception in this regard; in fact, it is one of the countries with the highest burden of several cancer types. Tens of thousands of cancer patients are newly dia­gnosed in the Czech Republic each year, and hundreds of thousands of them are followed up due to a history of cancer in the past [1]. This work aims to describe the epidemiological situation as well as epidemiological trends of plasma cell leukemia (PCL), which is a rare but the most aggressive form of monoclonal gammopathies. PCL is defined by the presence of more than 20% of plasma cells in the peripheral blood or the absolute plasma cell count > 2 × 109/ L [2]. PCL is classified as primary (pPCL) when it presents de novo in patients with no evidence of previous multiple myeloma (MM) and as secondary (sPCL) when it is observed as a leukemic transformation of relapsed or refractory dis­ease in patients with previously recognized MM [3]. About 60– 70% of PCL are pPCL, whereas the remain­ing 30– 40% are sPCL [4].

Materials and Methods

High-quality data play a key role in the evaluation of cancer epidemiology; in particular, the follow­ing two data sources [5] are used for this purpose in the Czech Republic.

First, data on demographic structure of the population of the Czech Republic are processed by the Czech Statistical Office (CZSO) as part of its monitor­ing activities. These data cover demographic characteristics of the population, such as the total population size, age structure, life expectancy etc. [6,7]. Population-based data on cancer mortality are stored in a database of causes of death, which is also processed by the CZSO in accordance with international methodology and based on data from death certificates (ICD-10 classification).

Second, the Czech National Cancer Registry (CNCR) is the main source of data on cancer epidemiology. Nowadays, the CNCR is an integral part of comprehensive cancer care, cover­ing 100% of the Czech population and contain­ing more than 2.3 million cancer cases recorded between 1977 and 2015. Accord­ing to CNCR data, the lifetime risk of develop­ing cancer is approximately 1/ 3 in the Czech population. However, PCL is a very rare dis­ease that only accounts for 0.02% of these records. In general, the registration of malignant tumors is enshrined in the Czech legislation and is obligatory. The CNCR is also the source of data for the assessment of basic performance indicators of cancer care, particularly for the assessment of patient survival. The Czech Society for Oncology has used CNCR data to develop an information system that predicts not only the population burden of cancer, but also treatment burden for future periods. Predictions of the population burden of cancer are based on modell­ing of the development of demographic structure and cancer incidence in the population. On the other hand, predictions of prevalence of cancer patients to be treated in the near future are based on survival models. The methodology and applied prediction scenarios are described in Dusek et al. [1].

Results

International comparison of PCL epidemiology

Due to relatively low incidence and prevalence rates of PCL, international epidemiological data are not available in commonly used databases, such as the GLOBOCAN database (http:/ / gco.iarc.fr/ ). Epidemiological estimates are therefore based on isolated studies. PCL is usually dia­gnosed in 2– 4% of MM patients [8,3–10]; this is consistent with our results from the CNCR (1977– 2015), where the ratio of PCL to MM patients is 3 : 100.

Epidemiology of MM in the Czech Republic

For the purpose of analysis of CNCR data, neoplasms with dia­gnosis C90.1 (accord­ing to the International Statistical Classification of Dis­eases and Related Health Problems –  10th Revision, ICD-10) and neoplasms with morphology code 9733/ 3 (accord­ing to the International Classification of Dis­eases for Oncology –  3^rd Edition, ICD-O-3) were included in the group of PCL. Nevertheless, available data do not distinguish between pPCL and sPCL; most cases of sPCL are therefore probably included under MM in CNCR data and cannot be distinguished as an independent dia­gnosis.

Trends in PCL incidence and mortality in the Czech Republic over more than three decades are shown in Graph 1. Both incidence and mortality rates decreased until approximately the year 2000 and have stabilized since then. The average annual incidence was 19 patients in the period 1997– 1999, and 6 patients in the period 2000– 2015. This downward trend can be probably attri­buted to dia­gnostics and cod­ing issues of this rare dia­gnosis. In absolute numbers, the incidence in 2015 was 6 persons (0.57 per million population), namely 5 men and 1 woman. In terms of mortality, 4 persons (0.38 per million population) died from PCL in 2015, all of them were men. The over­all epidemiological situation regard­ing PCL in the Czech Republic is summarized in Tab. 1. Data from the CNCR have shown that 4.5% of PCL cases (14.7% in the period 2000– 2015) were preceded by another cancer in the same patient.

The proportion of men and women with PCL was approximately the same. We have confirmed that PCL is mostly dia­gnosed in older people –  the median age was 66 years in men and 70 years in women, which is consistent with the median age of MM patients. Incidence rates were highest between the ages of 70 and 74 years in men and between the ages of 70 and 79 years in women (Graph 2). At the time of dia­gnosis, around 2% of all PCL patients were under the age of 45, and approximately 25% of all MM patients were under the age of 60. Age-specific incidence rates rise sharply from around the age of 45 (Graph 2) and thus demonstrate the grow­ing risk of develop­ing PCL in older age.

Graph 3 shows the comparison of PCL incidence in regions of the Czech Republic in the period 1977– 2015. Prague (capitol of the Czech Republic) reported the highest incidence of PCL (2.09 cases per million per year), whereas the Olomouc Region and the South Moravian Region had the lowest incidence (both regions reported 0.52 cases per 1 million per year).

Discussion

The epidemiology of rare dis­eases from CNCR data should be interpreted carefully, with awareness of data limitations. The quality of cod­ing of rare dia­gnoses is closely related to dia­gnostics of the dis­ease and the over­all awareness of the dis­ease. In general, there are two problems with PCL cod­ing in a population-based registry, such as the CNCR. First, the dis­ease is classified into two forms –  pPCL, which occurs without previously identified MM stage, and sPCL, which develops from previously dia­gnosed and treated MM [11]. We suppose that most reported cases of PCL are pPCL because sPCL is a relapse of a previously reported myeloma and, in most cases, is not coded as an independent dia­gnosis in the CNCR. More recent data suggest that the incidence of sPCL has increased, now account­ing for about 50% of the cases [12]; this might also influence the results. Second, the development of dia­gnostic criteria and laboratory techniques can influence the classification of PCL patients and therefore also the recorded epidemiology of the dis­ease. The first dia­gnostic criteria were defined in 1974 [13] and amended in 1987 [14]. The current dia­gnostic criteria, which originated in the 1970s, might underestimate the prevalence of PCL, and their re-evaluation is therefore be­ing considered [2].

Data from registries, such as the CNCR, can provide useful information on epidemiology of various dis­eases. These data, however, have several limitations, such as dia­gnostic criteria and proper cod­ing of not only the dis­ease itself, but also its various forms. These limitations have to be taken into account dur­ing the process of results interpretation.

Conclusion

The aim of this work was to describe the epidemiological situation as well as epidemiological trends of plasma cell leukemia. In the Czech Republic, an average of 6 people were newly dia­gnosed with PCL and about 4 people died from it between 2000 and 2015 each year. The ratio of PCL to MM patients is 3 : 100, which is a result comparable to international data.

The publication was supported by the ESF project CZ.03.4.74/0.0/0.0/15_019/0002748 Development of NZIS technological platform.

The authors declare they have no potential conflicts of interest concerning drugs, pro­ducts, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE recommendation for biomedical papers.

RNDr. Jiří Jarkovský, Ph.D.

Institute of Biostatistics and Analyses

Faculty of Medicine

Masaryk University

Kamenice 126/3

625 00 Brno

Submitted: 3. 1. 2019

Accepted 22. 1. 2019