Potter Progress in Myeloma

Biology of Myeloma 1980 Edition
1. Auflage 2013
ISBN: 978-1-4831-6153-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 302 Seiten

Progress in Myeloma: Biology of Myeloma is a collection of research studies dealing with the clinical and experimental plasma cell tumors. This work is composed of 14 chapters that provide a particularly advantageous basis for defining in biochemical and genetic terms the nature of critical alterations in the neoplastic transformation of immunoglobulin producing cells. The introductory chapters survey the epidemiology of multiple myeloma and related plasma cell disorders, as well as the mechanism of in vitro bone resorption by human myeloma cells. The subsequent chapters describe the clinical manifestations of the Waldenström's macroglobulinemia in black and white South Africans; myeloma models to evaluate the activation and suppression of normal lymphocytes; and the cellular and molecular mechanisms of murine myeloma cell growth and differentiation regulation. These topics are followed by discussions of the characteristics of multiple myeloma as an immunodeficiency disease, the myeloma growth kinetics, and the extent of clonal involvement in multiple myeloma. A chapter explores the use of anti-idiotypic antibodies in the regulation of the myeloma tumor cell growth and non-neoplastic B cell clones. The concluding chapters look into the chromosomal changes, therapeutic trials, and genetic basis of myeloma. This book will prove useful to oncologists, cell biologists, immunologists, and researchers.

Autoren/Hrsg.

Potter, Michael

Leseproben

Epidemiology of Multiple Myeloma and Related Plasma Cell Disorders: An Analytic Review

William A. Blattner, M.D.,     Environmental Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Publisher Summary

This chapter presents an analytical review of epidemiology of multiple myeloma and related plasma cell disorders. A variety of etiologic factors may contribute to the development of multiple myeloma and related dyscrasias. The major risk indicator is age, with myeloma being especially common at older ages. Similarly, BMG also manifests a parallel old-age pattern, which may be etiologically related. In the postulated two hit mutation model, BMG may be one manifestation of the first hit, representing the controlled proliferation of a clone of plasma cell synthesizing the M-spike. The second hit occurs when another mutation leads to uncontrolled malignant proliferation. An age-dependent loss of regulatory cell function may be involved in the first hit by increasing the pool of terminally differentiated, immunoglobulin-secreting cells potentially available for malignant transformation. This old-age determinant may also help explain why an excess has not been found in some occupational and high-risk cohort studies which are limited in extent of long-term follow-up. Race is another important determinant. The higher rate and earlier age of onset of myeloma in Blacks suggests an inborn susceptibility, although environmental factors cannot be excluded. This may correlate with racial differences in baseline immunoglobulin levels 40 and with altered patterns of cellular response to mitogens in Blacks.

Introduction

Epidemiologists have given limited attention to multiple myeloma and related disorders, whereas basic and clinical scientists have shown a long-standing and abiding interest. To the laboratory scientist, multiple myeloma is an experiment of nature that opens a biological window to normal and pathologic immune function; to the clinician, its protean manifestations are a continual challenge. In recent years, improvements in the diagnosis and reporting of myeloma have enabled the recognition of epidemiologic patterns that suggest opportunities for etiologic study.

Multiple Myeloma

From the first report of “Mr. McBean’s illness” in 1845,45 through the development of more precise clinical, pathologic, and laboratory methods, multiple myeloma has presented problems in classification and diagnosis. Myeloma was traditionally classified as a bone tumor until the sixth edition of the (ICD-6), published in 1949, when it was assigned rubric No. 203 under the category of “neoplasms of lymphatic and hematopoietic tissues.” The accuracy and ease of diagnosis was improved by the introduction of paper electrophoresis in the early 1950's. Thus, early epidemiologic studies were limited not only by imprecise nomenclature, but also by case underascertainment.

Multiple myeloma, as shown in Table I, is the prototype of a group of conditions known as “monoclonal gammopathies.” The most frequent form, “secretory myeloma,” is a malignant proliferation of plasma cells that secrete an essentially normal immunoglobulin product,296 usually IgG or IgA, but sometimes IgD and, rarely, IgE. In some cases, free light chains or Bence-Jones protein are produced alone or along with the complete immunoglobulin.

Table I

Classification of Monoclonal Gammopathies

In modern immunopathologic terms, multiple myeloma is classified as a malignancy of B-cell lineage (Figure 1).22,34 Recent studies from a number of laboratories, however, suggest that the malignant clone may not be confined solely to the bone marrow plasma cell compartment since populations of circulating peripheral blood as well as bone marrow lymphocytes have surface markers that cross react with the serum M-globulin. The finding of these so-called “idiotype-bearing lymphocytes” in peripheral blood may explain the early and wide dissemination of malignant cells in most cases of myeloma.1,104,110,112,160,194,231,251,298

Figure 1 Schema of B-cell differentiation.

Background Studies

Although the first case of was documented over 135 years ago,147 prehistoric cases are suggested in skeletal remains from archaeological digs.204 Some of these cases may be suspect because of the young age of the skeletons; but others, especially from so-called “senile skeletons,” probably represent genuine examples.

Geschickter and Copeland88 reviewed the demographic and clinical features of multiple myeloma based on 425 cases, including 13 of their own, derived from the literature traced from 1845.

Gilliam,90 using mortality data for 1949, was the first to report population-based crude death rates of 0.86 and 0.68 per 100,000 per year in white males and females and 0.89 and 0.54 per 100,000 per year in nonwhite males and females. MacMahon and Clark164 undertook the first population-based incidence survey, involving 279 new cases of multiple myeloma in Brooklyn, New York, from 1943 to 1952. Myeloma was more than twice as common in Blacks than Whites, with an earlier median age of diagnosis.

The Second National Cancer Survey,61 conducted between 1947 and 1948 in ten metropolitan centers in the U.S., reported crude incidence rates of 1.0 ier 100,000 for white males, 0.8 for white females, 1.9 for nonwhite males, and 0.8 for nonwhite females.

Reports by Waldenström292 and Martin175 provided risk estimates for myeloma in western Europe. In Sweden, there were 3.0 cases per 100,000 per year among the 200,000 inhabitants of Malmo over a 10-year period. This rate was high compared to the Brooklyn experience and probably reflected the special interest of the Scandinavian investigators in myeloma and the older age of the population under study. Although the rates for England and Sweden were similar, there was an unexplained discrepancy in median age (70-80 years in Sweden versus 50-60 years in England). An international comparison from 18 countries301 reported death rates of approximately 1.0 per 100,000 per year in most western countries, but substantially lower rates in France, Italy, Australia, and Japan.

Demographic Features

Multiple myeloma was once thought to be extremely rare, with an estimated frequency in the 1928 report of Geschickter and Copeland88 of less than 0.1% of all malignancies. With the widespread application of bone marrow aspiration and serum protein electrophoresis, multiple myeloma is more common than previously realized. Tables II and III give the incidence and percentage of total cancers for 29 forms of malignancy among Whites and Blacks in the Third National Cancer Survey, 1969-1971.48 In Whites, multiple myeloma ranked 20th, accounting for 1.1%, while for Blacks it ranked 11th, accounting for 7.2%. The age-adjusted incidence (1970 standard) in Whites was 4.0 in males and 2.7 per 100,000 in females, while for Blacks the rate was 8.1 in males and 6.5 in females. The most recent U.S. incidence rates, based on 1973-1976 data from the Surveillance, Epidemiology and End Results (SEER) Program, showed no change in Whites, but an increase in Blacks.315 Multiple myeloma is the most common form of malignancy in the lymphohematopoetic system in Blacks (33%), while it is the third most common in Whites (14.1%) (Figure 2).

Table II

Incidence of Multiple Myeloma in U.S. Whites and Percentage of Total Cancers, Ranked in Descending Order

aCases per 100,000 per year.

48

Table III

Incidence of Multiple Myeloma in U.S. Blacks and Percentage of Total Cancers, Ranked in Descending Order

aCases per 100,000 per year.

48

Figure 2 Relative proportion of lymphoreticular malignancy in Whites and Blacks.

A distinctive feature of multiple myeloma is the late age of onset. Except for chronic lymphocytic leukemia, multiple myeloma shows the strongest age dependence of any neoplasm.164 The age-specific incidence curves for the United States, 1969-1971, in males and females, Whites and Blacks, are shown in Figure 3. Peak incidence in Whites and Blacks occurs between 75 and 80; however, Blacks have higher rates for all age groups throughout life, except for black females 44 years and under.

Figure 3 Multiple myeloma, age-specific incidence for U.S., 1969-1971. SOURCE: 48

Multiple myeloma predominates in males, with the excess apparent for all groups after age 40 (Figure 3). The biologic basis of this excess is not known, although experimental animal studies suggest a role for male hormones in the induction of mouse plasmacytoma.109 Perhaps...