Fast Facts: Lymphoma

By C. Hatton, G. Collins and J. Sweetenham

Lymphoma affects all ages. Advances in diagnostic cellular and molecular techniques coupled with new treatment options are improving patient outcomes. This third edition of our bestselling 'Fast Facts: Lymphoma' distills the most important aspects of diagnosis and management into an up-to-date and highly accessible well-illustrated overview that includes: • a clear outline of the nature of lymphoma • the essentials of clinical presentation, biopsy and histology • a synopsis of current laboratory diagnostics, including immunophenotyping, cytogenetics and microarray technology, and updated to include the latest molecular genetic techniques • key aspects of staging and initial therapy • clearly illustrated overviews of the pathology, presentation, treatment and prognosis of each lymphoma subtype • new treatment options, including targeted biological therapies and chimeric antigen receptor T cells (CAR T cells) • a practical overview of supportive care for the complications of lymphoma. Written by three lymphoma experts from the UK and USA, 'Fast Facts: Lymphoma' gives an interesting international perspective to this challenging disease. Its clarity and colorful format make it a valuable resource for senior health professionals seeking an accessible update in this area of hemato-oncology, trainee doctors and specialist nurses who are new to it, and individuals affected by lymphoma and seeking more information. Contents: • Epidemiology • Cellular and molecular aspects • Presentation, biopsy and diagnostic laboratory techniques • Staging and general management principles • Aggressive B-cell lymphomas • Indolent B-cell lymphomas • T-cell and natural-killer cell lymphomas • Immunocompromised and HIV-positive patients • Hodgkin lymphoma • Treatment modalities • Supportive care

• Language: English
• Publisher: S. Karger
• Release date: Oct 16, 2018
• ISBN: 9781910797952

Book preview

Introduction

Lymphoma accounts for 4–5% of cancer diagnoses in the Western world. It affects all ages. In most cases, the disease can be controlled or even cured using chemotherapy, immunotherapy or radiotherapy either alone or in combination, although sadly some do still die of the disease. The field of lymphoma is rapidly changing and outcomes are improving. For example, two decades ago, a person with follicular lymphoma would have had a life expectancy of about 10 years. Today, this has doubled to nearer 20 years. Better supportive care is one reason for this improvement, but better outcomes are also a result of modern diagnostic techniques and more effective treatments. Underpinning these advances is the vastly improved clinical trial infrastructure. Most large cancer treatment centers offer an array of novel treatments, all administered through clinical trials under stringent governance procedures.

There has also been an unprecedented expansion in the knowledge of the molecular biology of many cancers. Lymphomas are among the best studied and understood. There is now a far greater understanding of the signaling pathways used by normal lymphocytes to carry out their functions, and a better understanding of how these pathways can go wrong and lymphoid cancer can develop. This allows drugs to be developed that target specific molecules known to be mutated or activated in individual lymphomas. In mantle cell lymphoma, for example, targeted therapy using an oral drug to block a specific enzyme, Bruton’s tyrosine kinase, results in many patients achieving sustained remissions when previously they have been resistant to chemotherapy.

There is also a growing appreciation of how the immune system can control and modulate cancers. This has been found to be very relevant in some lymphomas, notably Hodgkin lymphoma. Drugs that can modulate the immune system to help kill cancer cells are now routinely given to patients. Furthermore, the understanding of how T cells can kill cancer cells has enabled the development of bioengineered T cells designed to bind to and kill tumor cells. These chimeric antigen-receptor-modified T cells (CAR T cells) are being used to treat a number of different lymphomas, both within clinical trials and, increasingly now, for licensed indications outside of trials.

This new edition of Fast Facts: Lymphoma has been updated to include these latest advances in our understanding of the scientific basis of lymphoma together with the latest diagnostic techniques and treatments available to patients with this range of conditions.

Dedication

We had the privilege of knowing and working with Mandy Klyne, a talented and thoughtful editor who was closely involved in the production of the first edition of this text. Mandy’s personal experience, being affected by lymphoma herself, gave her a unique perspective and a deep understanding of this group of conditions. Her meticulous attention to detail, dedication to the education of healthcare practitioners and patients alike, and her warmth and good humor, made her the ideal colleague. She was taken from us too soon, and we dedicate this book to her memory.

Lymphoma is a malignancy of lymphocytes and their progenitors. The term lymphoma encompasses a broad range of lymphoid malignancies, reflected in the complexity of the classification systems (see Appendix). As recognized in the WHO classification system,¹ it is now understood that many of the broader categories of lymphoma, such as diffuse large B-cell lymphoma, include several distinct entities, each of which may have its own unique epidemiological and etiologic profile. Consequently, it is difficult to present an all-encompassing overview of the epidemiology of lymphoma.

Incidence and relevant factors

In the USA, Europe and Australasia the incidence of non-Hodgkin lymphoma (NHL) is approximately 20 per 100 000 of the population, with a slightly higher incidence in men than in women. This makes lymphoma the sixth or seventh most common cancer worldwide.

Age. Overall, incidence increases with age, although some subtypes of lymphoma are more common in children and young adults, such as Hodgkin lymphoma, anaplastic large-cell lymphoma and high-grade B-cell NHLs. Table 1.1 details some of the characteristics of lymphomas in children.

Sex. Although the overall incidence of lymphoma is 50% higher in men, this is not the case across all lymphoma entities. For example, mantle cell lymphoma particularly affects men (> 70% of cases), whereas primary mediastinal large B-cell lymphoma is more common in women.

Ethnicity. In the USA, the incidence of NHL is 50% higher in non-Hispanic white Americans than black Americans. However, in the UK, epidemiological data in white, Asian and black populations indicate no significant variation in incidence by ethnicity.

Geography. It has long been recognized that certain forms of lymphoma have an increased incidence in certain parts of the world (Figure 1.1). This association is particularly striking for endemic Burkitt lymphoma and adult T-cell leukemia/lymphoma (ATLL); however, similar associations are also well established for other subtypes. In some cases, the geographic distribution is at least partly explained by exposure to an etiologic factor – for example, ATLL occurs in areas with a high incidence of human T-cell lymphotropic virus-1 (HTLV-1; see Table 1.3). Overall, NHL is most common in the USA, Western Europe and Australia (possibly reflecting the age demographics of these populations). However, Hodgkin lymphoma is considerably more common in the Middle East, with incidence rates almost double those of Western Europe.

Figure 1.1 Geographic variation of non-Hodgkin lymphoma (NHL) subtypes. HTLV-1, human T-cell lymphotropic virus 1.

Changes in incidence. Between 1973 and 1990, the average age-adjusted incidence of NHL in the USA rose by 81%, from 10.2 to 18.5/100 0000,² with similar increases seen in Europe.³ This increase, observed in all racial groups and in both sexes, has been surpassed only by lung cancer in women and melanoma in both sexes, with specific etiologic factors identified for both of these (smoking and exposure to ultraviolet radiation, respectively). Recent age-adjusted data in the USA suggest, however, that since 1990 the incidence of NHL has plateaued (Figure 1.2). In contrast, data from the UK show a continued increase. Interestingly, the incidence of Hodgkin lymphoma has been stable for several decades.

Research into the reasons why the incidence of lymphoma increased so dramatically has failed to provide convincing answers. Improvements in diagnostic techniques and data registration for NHL are likely to have contributed, so the data should be interpreted with caution. However, the stability of the incidence of Hodgkin lymphoma argues against a purely artefactual increase.

Figure 1.2 The incidence of non-Hodgkin lymphoma in the USA has stabilized in recent years. Data from NIH National Cancer Institute.²

Risk factors

Risk factors for lymphoma can be divided into two broad categories:

• relatively uncommon risk factors that carry a high relative risk

• common risk factors that carry a low relative risk.

With the exception of HIV infection (see below), none of the risk factors is known to have changed over time.

Relatively uncommon risk factors with high relative risk. Immunodeficiency is the most obvious example of a relatively uncommon risk factor that carries a high relative risk. An increasing incidence of immunodeficiency during the 1980s and 1990s, most obviously because of the emergence of HIV and AIDS, has been suggested as a reason for the rising incidence of lymphoma. Indeed, HIV/AIDS has been shown to be a major risk factor for the development of lymphoma, though it accounts for less than 50% of the increase in incidence seen in the West and changes in HIV rates are not thought to have affected the recent stability of NHL incidence seen in the USA.⁴ Furthermore, the incidence of AIDS-associated lymphoma has declined since the advent of highly active antiretroviral therapy (HAART).

Common risk factors with low relative risk. Many environmental factors have been implicated in the development of lymphoma (see below). Most of these have been identified using case–control retrospective analyses, which have disadvantages, such as recall and selection bias, that can reduce the validity of the results.

Further large prospective cohort studies are needed, some of which are ongoing. However, it must be remembered that a relatively innocuous environmental exposure that carries only a marginally raised relative risk of developing lymphoma can contribute substantially to a rising incidence if a sufficiently large number of people are exposed. Nevertheless, it is not possible to test for every environmental exposure that carries only a marginally raised relative risk.

Environmental causes of non-Hodgkin lymphoma

Immunosuppression has two relatively common causes: HIV infection and immunosuppressive drug treatment.

HIV infection increases the risk of developing NHL more than 100-fold.⁵ The lymphomas, which are generally aggressive, are either diffuse large B-cell or Burkitt type (see Chapter 8).

Immunosuppressive drugs following solid organ transplantation are associated with a tenfold increased risk of developing NHL and a fourfold risk of developing Hodgkin lymphoma;⁶ Epstein–Barr virus (EBV) is often a cofactor. The drugs impair T-cell control of EBV-driven polyclonal B-cell activation, resulting in polyclonal B-cell proliferation. A dominant B-cell clone can then evolve, resulting in lymphoma (see Chapter 8).

Infection, both bacterial and viral (other than HIV), may be an acquired cause of lymphoma (Tables 1.2 and 1.3).⁷

Inflammatory conditions. Although not strictly an environmental cause, certain inflammatory conditions predispose to the development of NHL and particularly extranodal marginal zone/mucosa-associated lymphoid tissue (MALT) lymphomas, which are associated with organ-specific autoimmune conditions. For example, Sjögren syndrome (an autoimmune condition affecting the salivary and lacrimal glands) is associated with a 15-fold increased risk of developing salivary or lacrimal MALT lymphomas, and Hashimoto disease (an autoimmune condition affecting the thyroid gland) predisposes to thyroid MALT lymphoma.⁹

Figure 1.3 The Epstein–Barr virus (EBV), a member of the herpes virus family.

Pesticide/herbicide exposure has been implicated in the etiology of NHL in numerous studies.¹⁰ Agents include organophosphates, phenoxyacetic acid herbicides and triazine herbicides.