Page 1366 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 75

HODGKIN LYMPHOMA: CLINICAL MANIFESTATIONS,

STAGING, AND THERAPY

Katy Smith, April Chiu, Rahul Parikh, Joachim Yahalom, and Anas Younes

Hodgkin lymphoma (HL) is an uncommon lymphoproliferative Etiology
malignancy arising from B cells. It can affect all age groups but is
most common in young adults. HL is the first adult malignancy to The exact cause of HL remains unknown and clearly defined risk
demonstrate the curative potential of combination chemotherapy. factors for the development of the disease are lacking. However,
Today more than 80% of patients with newly diagnosed HL can now certain associations with its development have been identified.
expect to be cured of their disease. Although a clear genetic cause has not been established, familial
The challenge now, particularly since many affected patients are susceptibility has been suggested by both an apparent increased risk
young, is not only to improve cure rates further, but also to minimize among siblings of patients with HL, as well as concordance for HL
the risk of long-term complications of treatment, which can impact observed in monozygotic twins. Increased maternal education, early
quality of life and survival. Accordingly HL provides a very important birth order, low number of siblings and single-family dwellings in
clinical model for ongoing cancer research involving both the devel- childhood have all also been positively associated with the occurrence
opment of novel targeted agents and the study of late effects of cancer of HL in younger patients.
therapy. Epstein-Barr virus (EBV)−positive Reed-Sternberg (RS) cells are
Traditionally the choice of frontline therapy for HL has been found in approximately 40% of patients with HL using modern
determined by clinical stage and prognostic factors. A combined molecular techniques, mostly in cases of mixed cellularity classic HL
modality approach with chemotherapy and radiotherapy remains the (MCCHL) and lymphocyte-depleted classic HL (LDCHL), with
standard of care for those with early-stage disease, whereas chemo- reduced frequency observed in nodular sclerosis classic HL (NSCHL)
therapy alone is routinely used for those presenting with more and lymphocyte-rich classic Hodgkin Lymphoma (LRCHL). The
advanced clinical features. The availability of highly effective chemo- incidence of HL among those with a past history of EBV infection
therapy combinations and sensitive imaging tests has allowed the appears to be higher than those without previous exposure. EBV may
development of less toxic therapeutic strategies for those with limited play a role in promoting RS survival and has been associated with
disease. This includes the implementation of involved-field radio- the increased production of molecules that are involved in mecha-
therapy (IFRT), and more recently involved-site radiotherapy (ISRT), nisms of immune escape, in turn influencing the microenvironment
and a reduction in the number of chemotherapy cycles. This more that supports HL development.
focused treatment delivery has allowed efficacy to be preserved while The incidence of HL is higher in patients with human immuno-
exposure to unnecessary toxicity is reduced. deficiency virus (HIV) infection, suggesting a potential contributory
The management of HL continues to evolve. Positron emission role for immune suppression and reinforcing the likelihood of there
tomography (PET) imaging has emerged as a useful tool for assessing being an important immune component underlying HL pathogenesis
response and to guide further therapy that may allow radiation (see Special Considerations: Hodgkin Lymphoma in Patients with
therapy (RT)−free regimens. This, coupled with ongoing research to HIV Infection section, later).
identify better biologic prognostic factors, is likely to allow for a more
accurate risk-adapted approach to management, with the future
treatment of patients with HL being tailored to the needs of the PATHOBIOLOGY OF HODGKIN LYMPHOMA
individual. In addition, improved understanding of the molecular
mechanisms underlying HL has hastened the development of more The World Health Organization (WHO) classifies HL into two
effective, and often less toxic, targeted therapies for use either as distinct disease types: classic HL (cHL), representing 95% of all cases,
monotherapy or in combination with traditional chemotherapy to and nodular lymphocyte-predominant HL (NLPHL), accounting for
augment efficacy and decrease overall toxicity. only 5%. Both cHL and NLPHL are neoplasms composed of a minor
component of atypical large neoplastic cells, usually accounting for
<10% of all cells that are present in a reactive nonneoplastic back-
EPIDEMIOLOGY AND ETIOLOGY ground. However, based on their distinct clinical and molecular
genetic features, it is now evident that cHL and NLPHL are two
Incidence and Age of Onset biologically distinct entities. Within cHL, four histologic subtypes
are recognized based on the morphology of the neoplastic cells,
HL is a rare B-cell malignancy accounting for less than 1% of all composition of the nonneoplastic infiltrate, and overall nodal archi-
cancers with approximately 9200 new cases diagnosed in the United tecture: nodular sclerosing (NSCHL), mixed cellularity (MCCHL),
States and approximately 5500 new cases diagnosed in Europe each lymphocyte-depleted (LDCHL) and lymphocyte-rich (LRCHL). Of
year. The incidence of HL varies with economic status and geographic these, NSCHL predominates, accounting for 70% of cases of cHL
location. In developed countries it is associated with a bimodal age in Europe and the United States (Table 75.1). The rate of NSCHL,
of onset distribution, with an early, larger, peak occurring in young however, varies with geographic location and socioeconomic status
adults aged between 20 and 40 years and a second, smaller, peak and is much lower in developing countries, where MCCHL predomi-
occurring in those over 55 years. In contrast, in developing countries, nates. Furthermore, NSCHL occurs less frequently in patients
the disease predominantly occurs in childhood, with the incidence infected with HIV, among whom the more common presenting
decreasing with age. Overall, men are affected slightly more frequently subtype, again, is MCCHL (see Special Considerations: Hodgkin
than women (1.3 : 1). Lymphoma in Patients with HIV Infection section, later).

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