LYMPHOMA

The lymphomas are neoplasms of cells of lymphoid origin. These tumors

usually start in lymph nodes but can involve lymphoid tissue in the spleen,
GI tract (e.g., the wall of the stomach), liver, or bone marrow (see Fig. 35-
1 in Chapter 35). They are often classified according to the degree of cell
differentiation and the origin of the predominant malignant cell.
Lymphomas can be broadly classified into two categories: Hodgkin
lymphoma and non-Hodgkin lymphoma (NHL).

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Hodgkin Lymphoma
Hodgkin lymphoma is a relatively rare malignancy that has a high cure
rate. It is somewhat more common in men than in women and has two
peaks of incidence: one from age 15 to 34 and the other after 60 years of
age (Press, 2016). Disease occurrence has a familial pattern: First-degree
relatives have a higher-than-normal frequency of disease, but the actual
incidence of this pattern is low. No increased incidence for non-blood
relatives (e.g., spouses) has been documented. The 5-year survival rate is
90% for more limited disease (stage I or II), and 65% for those with more
extensive disease (stage IV) (ACS, 2015b).

Pathophysiology
Unlike other lymphomas, Hodgkin lymphoma is unicentric in origin in that
it initiates in a single node. The disease spreads by contiguous extension
along the lymphatic system. The malignant cell of Hodgkin lymphoma is
the Reed-Sternberg cell, a gigantic tumor cell that is morphologically
unique and thought to be of immature lymphoid origin (see Fig. 34-7). It is
the pathologic hallmark and essential diagnostic criterion. However, the
tumor is very heterogeneous and may actually contain few Reed-Sternberg
cells. The remaining tumor volume is composed of benign, reactive,
inflammatory cells that support the growth and survival of the Reed-
Sternberg cell (Batlevi & Younes, 2013). Repeated biopsies may be
required to establish the diagnosis.
The cause of Hodgkin lymphoma is unknown, but a viral etiology is
suspected. Although fragments of the Epstein-Barr virus have been found
in some Reed-Sternberg cells, the precise role of this virus in the
development of Hodgkin lymphoma remains unknown. Other viruses may
also be implicated, including human immune deficiency virus (HIV) and
herpesvirus 8. Hodgkin lymphoma is seen more commonly in patients
receiving chronic immunosuppressive therapy (e.g., for renal transplant)
and also in veterans of the military who were exposed to the herbicide
Agent Orange (Leukemia & Lymphoma Society, 2013).
Hodgkin lymphoma is customarily classified into five subgroups based
on pathologic analyses that reflect the natural history of the malignancy
and suggest the prognosis. For example, when lymphocytes predominate,
with few Reed-Sternberg cells and minimal involvement of the lymph
nodes, the prognosis is much more favorable than when the lymphocyte

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count is low and the lymph nodes are virtually replaced by tumor cells of
the most primitive type. Most patients with Hodgkin lymphoma have the
types currently designated as “nodular sclerosis” or “mixed cellularity.”
The nodular sclerosis type tends to occur more often in young women, at
an earlier stage, and is often cured by therapy. The mixed cellularity
subgroup occurs more commonly in men and older individuals; it is
associated with more constitutional symptoms, advanced stage disease,
and immunodeficiency (Press, 2016).

Figure 34-7 • Reed-Sternberg cell. Reed-

Sternberg cells are large, abnormal
lymphocytes that may contain more than one
nucleus. These cells are found in Hodgkin
lymphoma. Adapted with permission from
Rubin, R., Strayer, D. S., & Rubin, E. (2011).
Rubin’s pathology (6th ed.).Philadelphia, PA:
Lippincott Williams & Wilkins.

Clinical Manifestations
Hodgkin lymphoma usually begins as an enlargement of one or more
lymph nodes on one side of the neck. The individual nodes are painless
and firm but not hard. The most common sites for lymphadenopathy are
the cervical, supraclavicular, and mediastinal nodes; involvement of the
iliac or inguinal nodes or spleen is much less common. A mediastinal mass

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may be seen on chest x-ray; occasionally, the mass is large enough to
compress the trachea and cause dyspnea. Pruritus is common; it can be
extremely distressing, and the cause is unknown. Some patients experience
brief but severe pain after drinking alcohol, usually at the site of the tumor.
The cause of this symptom is also unknown.
All organs are vulnerable to invasion by tumor cells. The symptoms
result from compression of organs by the tumor, such as cough and
pulmonary effusion (from pulmonary infiltrates), jaundice (from hepatic
involvement or bile duct obstruction), abdominal pain (from splenomegaly
or retroperitoneal adenopathy), or bone pain (from skeletal involvement).
Herpes zoster infections are common. A cluster of constitutional
symptoms has important prognostic implications. Referred to as B
symptoms, they include fever (without chills), drenching sweats
(particularly at night), and unintentional weight loss of more than 10% of
body weight. B symptoms are found in 40% of patients, and are used in
part in deciding appropriate treatment (Cheson, Fisher, Barrington, et al.,
2014). A mild anemia is the most common hematologic finding. The
leukocyte count may be elevated or decreased. The platelet count is
typically normal, unless the tumor has invaded the bone marrow,
suppressing hematopoiesis. The erythrocyte sedimentation rate (ESR)
and the serum copper level are sometimes used to assess disease activity;
elevations may reflect increases in disease activity. Patients with Hodgkin
lymphoma have impaired cellular immunity, as evidenced by an absent or
decreased reaction to skin sensitivity tests (e.g., Candida, mumps).
Infections, including viral infections, are common (see Fig. 34-8).

Assessment and Diagnostic Findings

Because many manifestations are similar to those occurring with infection,
diagnostic studies are performed to rule out an infectious origin of the
disease. The diagnosis is made by means of an excisional lymph node
biopsy and frequently, the finding of the Reed-Sternberg cell. Once the
diagnosis is confirmed and the histologic type is established, it is necessary
to assess the extent of the disease—a process referred to as staging.
During the health history, the patient is assessed for any B symptoms.
Physical examination requires a careful, systematic evaluation of all
palpable lymph node chains (see Fig. 32-4 in Chapter 32), as well as the
size of the spleen and liver. A chest x-ray and a computed tomography
(CT) scan of the chest, abdomen, and pelvis are crucial to identify the

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extent of lymphadenopathy within these regions. A positron emission
tomography (PET) scan may be the most sensitive imaging test in
identifying residual disease and is being evaluated for its predictive value
in this disease (Evens & Kostakoglu, 2014). Laboratory tests include CBC,
platelet count, ESR, and liver and renal function studies. A bone marrow
biopsy is not routinely performed (Cheson et al., 2014).

Figure 34-8 • Herpes zoster is a common

complication in patients with
lymphoproliferative disease, such as Hodgkin
lymphoma here. Zoster infections are also
common in patients on chronic steroid use for
hematologic conditions and some
chemotherapy regimens. From Tkachuk, D.
C., & Hirschman, J. V. (2007). Wintrobe’s
atlas of clinical hematology (Fig. 5.152, p.
207). Philadelphia, PA: Lippincott Williams
& Wilkins.

Medical Management
The goal in the treatment of Hodgkin lymphoma is cure. Cure rates are
85% to 90% for patients with early-stage disease and 65% to 85% for
those with advanced-stage disease (Matasar, Ford, Riedel, et al., 2015).
Treatment is determined primarily by the stage of the disease, not by the

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histologic type; however, extensive research is ongoing to target treatment
regimens more to the histologic subtypes or prognostic features. Because
of long-term survival and potential for cure from the disease, consideration
must be made of potential long-term morbidity associated with treatment,
particularly cardiac disease and second malignancies. Treatment choice
must be balanced between using high-intensity therapy, where the
likelihood of cure or long-lasting remission is high but has a risk of late
toxicity and potential mortality, and less-intensive therapy that may have
less toxicity but greater likelihood of relapsed disease. This dilemma is
particularly relevant when treating young patients with early-stage disease
(Johnson, 2013).
Treatment of limited-stage Hodgkin lymphoma commonly involves a
short course (2 to 4 months) of chemotherapy followed by radiation
therapy to the specific involved area. This strategy has reduced the
radiation dosage, with subsequent decrease in long-term side effects
(particularly second malignancies and late cardiovascular events) and
without decreasing the likelihood of controlling the disease. However,
with the effectiveness of second-line therapies, even this amount of
radiation is being questioned (Johnson, 2013). Combination chemotherapy
with doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine
(Velban), and dacarbazine (DTIC), referred to as ABVD, is considered the
standard treatment for more advanced disease (stages III and IV and all
stages with B symptoms). Chemotherapy is often successful in obtaining
remission even when relapse occurs. Other combinations of chemotherapy
are used, which may have more toxicity. The MoAb brentuximab vedotin
(Adcetris) has approval for use in refractory relapsed Hodgkin lymphoma.
This drug targets a receptor that is expressed on the surface of activated T
and B lymphocytes, but also on Reed-Sternberg cells. Current studies are
ongoing to determine the best time to use this therapy: prior to transplant
(HSCT), as maintenance therapy post-transplant, or when transplant is not
an option (Graf & Gopal, 2014).
HSCT is used for advanced or refractory disease. Most patients
diagnosed with Hodgkin lymphoma are either cured or experience
prolonged remissions, and thus live for many years post diagnosis. As a
result, much is now known about the long-term effects of chemotherapy
and radiation therapy. Second malignancies are the leading cause of death
in long-term survivors of Hodgkin lymphoma (Ng, 2014). There is a
latency period of 5 years, after which time the risk progressively increases

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and remains greater than would be expected in the general population, at
least 25 years after diagnosis (Ng, 2014). In a study of 465 adults
previously treated for Hodgkin lymphoma, the risk of developing a
nonfatal second malignancy was 3.41 times higher (Matasar et al., 2015).
The most common to develop are breast, lung, GI, and skin cancers. Prior
radiation therapy is more closely associated with the development of
secondary cancers, but chemotherapy that used alkylator drugs is
associated with lung and GI cancer development (Ng, 2014). Leukemia
more commonly developed in patients who received the chemotherapy
regimen MOPP (i.e., nitrogen mustard, vincristine, procarbazine, and
prednisone).
Cardiovascular disease is also frequently seen in the Hodgkin
lymphoma survivor population. The risk develops after a latency of 10
years after diagnosis and is directly related to doses of radiation to the
anterior chest region. Coronary artery disease, dysrhythmias, valvular
disease, and cardiomyopathy are noted after radiation; congestive heart
failure, decreased systolic function, and dilated cardiomyopathy are more
commonly associated with prior anthracycline therapy (Ng, 2014).
Other organ dysfunction is also well documented, including that of the
endocrine system. A high incidence of anxiety and depression that also
persist over time was reported in several studies (Matasar et al., 2015;
Oerlemans, Mols, Nijziel, et al., 2014). Persistent fatigue is common in
survivors and can be exacerbated by depression and other treatment-
related comorbidities (Daniëls, Oerlemans, Krol, et al., 2013; Daniëls,
Oerlemans, Krol, et al., 2014; Soares, Biasoli, Scheliga, et al., 2013). Chart
15-4 in Chapter 15 lists long-term potential complications associated with
chemotherapy or radiation therapy.
Late effects of treatment can have an adverse effect on a survivor’s
quality of life (Oerlemans et al., 2014; Khimani, Chen, Mauch, et al.,
2013). A study of 40 young adult survivors found improvements in quality
of life as soon as 1 month after completing therapy, and this improvement
was still noted 6 months after therapy (Roper, Cooley, McDermott, et al.,
2013). These data need to be replicated in larger studies and for longer
periods of time; it may be that early improvements in quality of life do not
persist long term, particularly as late complications arise. Adequate social
support and social network are associated with better quality of life
(Soares et al., 2013).

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Nursing Management
The potential development of a second malignancy should be addressed
with the patient when initial treatment decisions are made. However,
patients need to be informed that Hodgkin lymphoma is often curable. The
nurse should encourage patients to reduce factors that increase the risk of
developing second cancers, such as use of tobacco and alcohol and
exposure to environmental carcinogens and excessive sunlight. Screening
for late effects of treatment (see Chart 15-4, Chapter 15) is necessary. In
addition, the nurse should provide education about relevant self-care
strategies and disease management. See also the Nursing Management
Section for Non-Hodgkin Lymphoma.

Non-Hodgkin Lymphomas
The NHLs are a heterogeneous group of cancers that originate from the
neoplastic growth of lymphoid tissue. Similar to CLL, the neoplastic cells
are thought to arise from a single clone of lymphocytes; however, in NHL,
the cells may vary morphologically. Eighty-five percent of NHLs involve
malignant B lymphocytes; the remaining 15% primarily involve T
lymphocytes (ACS, 2015c). In contrast to Hodgkin lymphoma, the
lymphoid tissues involved are largely infiltrated with malignant cells. The
spread of these malignant lymphoid cells occurs unpredictably, and true
localized disease is uncommon. Lymph nodes from multiple sites may be
infiltrated, as may sites outside the lymphoid system (extranodal tissue;
see Fig. 34-9).
NHL is the sixth most common type of cancer diagnosed in the United
States; incidence rates have almost doubled in the past 35 years. The
incidence increases with each decade of life; the median age at diagnosis is
66 years (Leukemia & Lymphoma Society, 2015b). Although no common
etiologic factor has been identified, the incidence of NHL has increased in
people with immunodeficiencies or autoimmune disorders; prior treatment
for cancer; prior organ transplant; viral infections (including Epstein-Barr
virus and HIV); and exposure to pesticides, solvents, dyes, or defoliating
agents, including Agent Orange. The overall survival rate is 69% at 5
years, and 59% at 10 years (ACS, 2015d).

Clinical Manifestations
Symptoms are highly variable, reflecting the diverse nature of the NHLs.

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Lymphadenopathy is the most common; however, in indolent types of
lymphomas, the lymphadenopathy can wax and wane. With early-stage
disease, or with the types that are considered indolent, symptoms may be
virtually absent or very minor, and the illness typically is not diagnosed
until it progresses to a later stage, when the patient is symptomatic. At
these stages (III or IV), lymphadenopathy is distinctly noticeable. One
third of patients with NHLs have B symptoms (fever, drenching night
sweats, and unintentional weight loss). Lymphomatous masses can
compromise organ function. For example, a mass in the mediastinum can
cause respiratory distress; abdominal masses can compromise the ureters,
leading to renal dysfunction; and splenomegaly can cause abdominal
discomfort, nausea, early satiety, anorexia, and weight loss.

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Figure 34-9 • Any extranodal location can
be a site for diffuse B-cell lymphoma, such as
the thyroid, as shown here. From Tkachuk, D.
C., & Hirschman, J. V. (2007). Wintrobe’s
atlas of clinical hematology (Fig. 5.87, p.
183). Philadelphia, PA: Lippincott Williams
& Wilkins.

Assessment and Diagnostic Findings

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The actual diagnosis of NHL is categorized into a highly complex
classification system based on histopathology, immunophenotyping, and
cytogenetic analyses of the malignant cells (see Table 34-4). The specific
histopathologic type of the disease has important prognostic implications.
Treatment also varies and is based on these features. Indolent types tend to
have small cells that are distributed in a circular or follicular pattern.
Aggressive types tend to have large or immature cells distributed through
the nodes in a diffuse pattern. Staging is typically based on data obtained
from CT and PET scans, bone marrow biopsies, and occasionally
cerebrospinal fluid analysis. The stage is based on the site of disease and
its spread to other sites. For example, in stage I disease, only one area of
involvement is detected; thus, stage I disease is highly localized and may
respond well to localized therapy (e.g., radiation therapy). In contrast, in
stage IV, disease in at least one extranodal site is detected.

TABLE 34-4 Types of Lymphomasa

Although the stage of disease is important, often it is not an accurate

predictor of prognosis. Two prognostic classification systems have been
developed that are particularly useful in the older patient population: the
International Prognostic Index (IPI) and, for follicular lymphomas, the

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Follicular Lymphoma International Prognostic Index (FLIPI). Age,
performance status, lactate dehydrogenase levels, stage of disease, and
extranodal involvement are scored to determine risk of failure or death
from disease. Based on the IPI, 5-year overall survival rates range from
75% (low risk) to 30% (high risk), and, based on the FLIPI, from 91%
(low risk) to 53% (high risk) (ACS, 2015e).

Medical Management
Treatment is determined by the classification of disease, the stage of
disease, prior treatment (if any), and the patient’s ability to tolerate
therapy. Tolerance to therapy is largely dictated by renal, hepatic, and
cardiac function; the presence of concurrent diseases; functional status;
and age. If the disease is not aggressive and is localized, radiation alone
may be the treatment of choice. With aggressive types of NHL, aggressive
combinations of chemotherapeutic agents are used; R-CHOP—the
combination of the MoAb rituximab with conventional chemotherapy
(cyclophosphamide, doxorubicin, vincristine, and prednisone)—is now
considered standard treatment for common lymphomas (Martelli, Ferreria,
Agostinelli, et al., 2013). CNS involvement is common with some
aggressive forms of NHL; in this situation, cranial radiation or intrathecal
chemotherapy is used in addition to systemic chemotherapy. Survival is
very low when relapse occurs after being treated with rituximab-based
regimens or with HSCT (Martelli et al., 2013).
More indolent lymphomas, such as follicular lymphoma, are not
currently curable. However, the pace of the disease is slow and many
patients have no or fewer symptoms at the time of diagnosis. “Watchful
waiting,” where therapy is delayed until symptoms develop, has often been
used in those with indolent disease (Izutsu, 2014). More recently,
immunotherapy (e.g., rituximab) is being used, often in combination with
conventional chemotherapy, followed by rituximab as “maintenance
therapy” (Hiddemann & Cheson, 2014; Izutsu, 2014). Patients with limited
stage disease may be effectively treated with radiation therapy to the
affected area.
Radiopharmaceutical agents (e.g., ibritumomab tiuxetan [Zevalin] or
tositumomab/iodine-131 [Bexxar]) are also used, although they cause
technical difficulties with administration due to the radioactivity of the
agent. More aggressive treatment (often R-CHOP or rituximab plus
bendamustine) may provide a longer duration of remission in which

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additional treatment is not needed. Unfortunately, in most situations,
relapse is commonly seen in patients with low-grade lymphomas.
Treatment after relapse is controversial; HSCT may be considered for
patients younger than 60 years (see Chapter 15).

Nursing Management
Lymphoma is a highly complex constellation of diseases. When caring for
patients with lymphoma, it is extremely important for the nurse to know
the specific disease type, stage of disease, treatment history, and current
treatment plan. Most of the care for patients with Hodgkin lymphoma or
NHL takes place in the outpatient setting, unless complications occur (e.g.,
infection, respiratory compromise due to mediastinal mass). The most
commonly used treatment methods are chemotherapy (often combined
with an MoAb) and radiation therapy. Chemotherapy causes systemic side
effects (e.g., myelosuppression, nausea, hair loss, risk of infection),
whereas radiation therapy causes specific side effects that are limited to
the area being irradiated. For example, patients receiving abdominal
radiation therapy may experience nausea and diarrhea but not hair loss.
Regardless of the type of treatment, all patients may experience fatigue
(see Chart 15-7 in Chapter 15, Fatigue).
The risk of infection is significant for these patients, not only from
treatment-related myelosuppression but also from the defective immune
response that results from the disease itself. Patients need to be educated to
minimize the risks of infection, to recognize signs of possible infection,
and to contact their primary provider if such signs develop (see Chart 15-7
in Chapter 15, Infection).
Additional complications depend on the location of the lymphoma.
Therefore, the nurse must know the tumor location so that assessments can
be targeted appropriately. For example, patients with lymphomatous
masses in the upper chest should be assessed for superior vena cava
obstruction or airway obstruction, if the mass is near the bronchus or
trachea.
Patient education is an integral component of nursing care. A
longitudinal study of more than 1,000 patients with various types of
lymphoma confirmed that informational needs vary over the course of the
survival trajectory (Husson, Oerlemans, Mols, et al., 2014). Those patients
diagnosed with lymphoma within the past 2 years voiced the need for
disease and medical information; whereas, those diagnosed beyond 2 years

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voiced the need for information related to long-term effects of therapy.
These results lend credence to the importance of tailoring information
provided to the unique learning needs of the patient, as well as the coping
styles that patient uses in living with lymphoma.
Many lymphomas can be cured with current treatments. However, as
survival rates increase, the incidence of second malignancies, particularly
AML or MDS, also increases. Therefore, survivors should be screened
regularly for the development of second malignancies. As is true with
long-term survivors of Hodgkin lymphoma, survivors of NHL may be
faced with managing persistent fatigue, depression, anxiety, cardiac, and
pulmonary toxicity (Spector, Noonan, Mayer, et al., 2015). A study of
quality of life among survivors of diffuse large B cell lymphoma found
that younger-aged survivors (18 to 59 years of age) reported worse
cognitive and social function and more financial problems and dyspnea
compared to age-matched controls (van der Poel, Oerlemans, Schouten, et
al., 2014). In contrast, the reported quality of life of older-aged survivors
was similar to those of the control group, albeit lower than those of the
younger-aged survivor group.
The American Cancer Society developed health behavior
recommendations for cancer survivors, which include avoiding smoking,
maintaining a normal body mass index (BMI), improving nutrition (i.e.,
consuming fruits and vegetables), and engaging in at least 150 minutes of
aerobic physical activity per week. However, many survivors do not
adhere to these recommendations. A study of more than 500 lymphoma
survivors found that only 11% adhered to all four recommendations
(Spector, et al., 2015). While most of these survivors reported they did not
smoke (94%), 52% reported they did not adhere to the activity
recommendations, 56% did not adhere to the dietary recommendations,
and 64% were overweight or obese. Those individuals who did adhere to
all four health behavior recommendations reported higher health-related
quality of life (HRQOL) than those who did not. HRQOL scores were
more strongly associated with nonsmoking and exercise adherence. These
data provide useful information for nurses in assisting patients to adapt and
adhere to healthy lifestyles upon completing treatment for lymphoma.

MULTIPLE MYELOMA
Multiple myeloma is a malignant disease of the most mature form of B

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