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Quality of Life in Low-Grade Non-Hodgkin’s Lymphoma

Quality of Life in Low-Grade Non-Hodgkin’s Lymphoma

ABSTRACT: Low-grade non-Hodgkin’s lymphoma (NHL) is an indolent form of the disease with a generally slow course of progression. Although still usually incurable, low-grade disease has shown responsiveness to some of the newer chemotherapeutic and nonchemotherapeutic treatment options. However, since cure remains elusive, and since many patients with low-grade NHL may have few or even no symptoms initially, the decision about whether or not to initiate treatment logically must include quality-of-life (QOL) issues. This paper summarizes clinical and diagnostic characteristics of low-grade NHL that have some bearing on QOL considerations. Adverse effects of the more common treatment approaches are discussed according to their QOL implications, illustrating the relevance of QOL to the clinical management of low-grade disease. Finally, data from an ongoing study using the Functional Assessment of Cancer Therapy (FACT) measurement system are presented. These data offer a basis for comparing the QOL of patients with NHL to that of individuals with other solid tumors, and also illustrate the effects of chemotherapy on QOL.[ONCOLOGY 12(5): 697-717, 1998]

In 1997, an estimated 54,000 people in the United States were
diagnosed with non-Hodgkin’s lymphoma (NHL).[1] This disease
thus accounted for nearly 4% of cancer incidence overall.[1] In the
same year (1997), almost 24,000 people died of the disease.[1]

The subclassification of low-grade NHL constitutes approximately 25%
of all cases.[2] Incidence of low-grade disease is higher in people
between the ages of 35 and 64 years (37%) than in those under age 35
(16%).[3] Ironically termed the “favorable” or indolent
form of NHL due to a natural history characterized by slow disease
progression and a relatively long duration of survival (7 to 10
years)[4] when compared to intermediate- and high-grade disease,
low-grade NHL is still regarded as essentially incurable.[5,6]

The addition of new treatment options, a better understanding of
factors that predict response, and the introduction of new
nonchemotherapeutic therapies have improved the clinical management
of low-grade NHL. These improvements have not yet produced a
significant increase in cure rate, however.[7-9] For this reason, and
because life-extending treatments produce toxicity and added cost,
quality of life (QOL) emerges as a very relevant consideration when
judging therapeutic benefit.

The course of progressive low-grade NHL is typified by sequential
remissions and relapses, disease dissemination, and eventual
resistance to current treatment approaches.[6] Also, since patients
often opt for alternative treatments at times of relapse, they are
likely to endure acute and chronic treatment toxicity, as well as
psychosocial sequelae associated with chronic, life-threatening disease.

In summary, given that the disease produces symptoms, the chance for
cure is low, and available treatments have a questionable impact on
survival and known toxicity (or cost), QOL may be the most important
clinical management concern. To date, however, there has been a
paucity of relevant literature and research on the quality of life of
patients with low-grade lymphoma, and no published randomized
clinical trial has included QOL evaluation as an outcome. The need
for reliable, valid measures of the physical, functional, emotional,
and social impact of lymphoma is apparent. Although questionnaires
that measure general QOL are available,[10-12] there is no lymphoma-specific
QOL questionnaire or subscale that addresses the particular symptoms
or concerns of patients with lymphoma or the effects of lymphoma
treatments on life quality. Treatment decision-making (by both
patient and physician) and practice guidelines would be enhanced by
the ability to balance QOL consequences against the known benefits
and drawbacks of established and investigational treatments, such as
extension of survival time, durability of remission, toxicity of
treatment, and effectiveness of palliation.

This paper will summarize the clinical characteristics of low-grade
NHL, including classification, staging, and symptoms, as well as the
predictors of treatment response. Adverse effects of the most common
treatments and their QOL implications will also be discussed, in an
attempt to illustrate the high degree of relevance of QOL
considerations to clinical management. In addition, the psychosocial
sequelae of NHL will be reviewed. Finally, data derived from a
commonly used questionnaire, the Functional Assessment of Cancer
Therapy (FACT) measurement system,[10] will be presented. These data
were used to compare the QOL of patients with NHL to a matched sample
of patients with mixed cancer types and a smaller sample of patients
with Hodgkin’s disease; the QOL of NHL patients according to
treatment status (on vs off chemotherapy) were also compared.

Clinical Characteristics

Classification and Staging
Non-Hodgkin’s lymphomas comprise a wide range of malignancies
that originate in the lymphoid system. They differ according to their
pathologic and immunologic characteristics and their prognostic
classification.[3,5,6] Efforts have been made to create a taxonomy
that effectively groups all lymphomas into distinct categories
according to their morphology, course, and outcome. Due to the
variability of lymphomas, however, development of a pure
classification system still remains challenging.[6]

At present, NHLs are commonly classified by the International Working
Formulation, established in 1982 by a special task force of the
National Cancer Institute to consolidate lymphomas by clinically
useful criteria so as to predict biological behavior, curability, and
survival.[13] Another classification system, the revised
European-American classification of lymphoid neoplasms (REAL) has
been proposed but is not universally accepted.[14] Precise diagnostic
evaluation of the histologic subtype and classification have become
critical for appropriate management of the disease.[6]

The International Working Formulation defines three general
categories of lymphomas—low grade, intermediate grade, and high
grade—which are differentiated most notably by their
aggressiveness or “malignant potential.”[5] Low-grade
lymphomas include small lymphocytic; follicular, small cleaved cell;
and follicular, mixed, small cleaved and large cell subtypes, which
are indolent by nature and initially responsive to a variety of
treatments but eventually prove nonresponsive.[6]

Non Hodgkin’s lymphoma is clinically staged using the Ann Arbor
staging classification (stage I, II, III, IV), which indicates the
extent to which lymph node regions and extralymphatic sites are involved.[15]

An unusual increase in the incidence of NHL since the 1970s,[5]
combined with little improvement in relative survival rates,
continues to challenge the medical community,[1] despite the
availability of diverse treatment options. Risk factors associated
with low-grade lymphomas include increasing age, male gender,
exposure to chemotherapy and radiation, and chronic
immunosuppression.[3,5] Of particular importance to QOL are practice
guidelines based on poor prognostic factors, such as age.

Diagnostic procedures to determine the type of lymphoma and extent of
disease are quite extensive, and often require that patients undergo
a variety of invasive and noninvasive tests, procedures, and surgical
explorations. Physical examination, peripheral lymph node biopsies,
chest x-rays, computed tomographic (CT) scans, bilateral bone marrow
biopsy, spinal taps, blood tests, and surgical evaluation of tissue
and organ involvement collectively lead to an accurate diagnosis.[3,5]

Repeat assessments are necessary to determine response to treatment
and guide therapeutic decisions. Chronic invasive assessments in
patients with hematologic malignancies cause discomfort and are
associated with heightened anxiety, especially at follow-up visits,
where fear of recurrence may be confirmed.[16]

Disease symptoms include both common lymphoma symptoms that are
indicative of active disease and specific symptoms highly influenced
by the location(s) and extent of disease dissemination.[5] The
majority of patients present initially with asymptomatic adenopathy
(lymph node swelling) and may have active disease without symptoms
for up to 3 years after diagnosis, making early treatment (for some)
optional.[17] The indolent nature of the low-grade subtypes may also
allow some patients to live a relatively prolonged symptom-free and
active life until the disease progresses.

Nonspecific lymphoma symptoms, commonly referred to as B symptoms,
include fatigue, fever, weight loss, and drenching night sweats.
These symptoms are prognostically unfavorable and therefore are often
an indication for treatment.[18] Other relevant symptoms include pain
and cosmetic problems due to enlarged lymph nodes.

Independent of prognostic differences, treatment of symptomatic
disease is more easily justifiable than treatment of asymptomatic
disease, on QOL grounds. This will be addressed below.

Site-specific involvement can be limited or widespread, can occur
anywhere in the lymphatic system (eg, lymph nodes, spleen, and bone
marrow), and can spread to one or more extralymphatic organs (eg,
stomach, intestine, bone, skin, oral cavity, and pharynx).[3,5] The
presence of bulky masses causes discomfort and often pain.

Other symptoms vary and may include abdominal pain, ulcers, or
bleeding if the gastrointestinal (GI) tract is involved.[5] If there
is throat or sinus involvement, head and neck discomfort, throat
pain, or swallowing difficulty can occur.[5] Patients with neurologic
or musculoskeletal system involvement may experience neurologic and
musculoskeletal pain and muscle weakness. With bone marrow
involvement, weakened immunity or chronic infections can develop.[3]

In short, the range of possible symptoms and functional problems
associated with low-grade NHL is diverse, and depends on the site and
degree of involvement. Progressive disease dissemination to
additional sites places patients at increased risk for new symptoms
and problems, which are often unpredictable, although manageable with
palliative therapies.


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