The following excerpt is taken from Chapter 18 of
Non-Hodgkin's Lymphomas: Making Sense of Diagnosis, Treatment, and
Options by Lorraine Johnston, copyright 1999 by O'Reilly & Associates,
Inc. For book orders/information, call (800) 998-9938. Permission is
granted to print and distribute this excerpt for noncommercial use as
long as the above source is included. The information in this article is
meant to educate and should not be used as an alternative for
professional medical care.
Fear of relapse is a nightmare that all of us experience at one time or
another. Unfortunately, for some of us there comes a day when the nightmare
is still there when we awake.
Depending on the subtype of NHL we have, and what we've learned about
it, we may be well prepared intellectually and emotionally for relapse,
perhaps with a new treatment plan already selected. Others among us may be
utterly broadsided by the news.
This article will begin with a definition of relapse, and then will
describe who is likely to relapse, how relapse is detected, in what areas
of the body relapse may occur, when it's most likely, and why it occurs.
There are indeed instances of test results mistakenly being interpreted as
relapse--and we'll discuss what findings may constitute equivocal
results--but chiefly this article will focus on true relapse. A discussion
of the difficult emotional issues that arise upon relapse, which often are
different from those we encounter at first diagnosis, will follow.
Relapse is the return of disease in a patient who had achieved and
maintained a complete remission--defined as the disappearance of all
disease--for longer than thirty days after treatment ended.
If signs of disease recur in a survivor who achieved a partial
remission-- greater than 50 percent reduction in tumor size--the return of
disease is called disease progression, rather than relapse, because full
remission was never realized.
If signs of disease return within thirty days following treatment, then
by definition no remission was achieved, regardless of the amount of tumor
shrinkage observed during treatment.
Tumors that shrink, but neither disappear nor regrow, are categorized as
a type of partial remission called stable disease.
It's possible to mistake the after-effects of treatment for symptoms of
The most widely accepted theory for relapse is that not all lymphoma
cells were killed by the original treatment. Other theories hold that
genetic predisposition, continued or recurrent exposure to environmental
toxins, or unabated or repeated exposure to an infectious agent are
responsible for relapse. Interesting research has been done showing that
cancer cells can acquire resistance to chemotherapeutic drugs by turning on
genes that block the cellular intake of certain drugs and others related to
them, a phenomenon called multiple drug resistance (MDR).
Nonetheless, successes with high-dose treatment followed by bone marrow
transplantation or bone marrow rescue suggest that the lingering cancer
cell theory is correct.
Some NHL survivors detect swollen nodes, or experience old, familiar
feelings of malaise, or notice other recurrent symptoms. These very
frightening findings trigger a visit to their oncologist. Other survivors
note entirely new symptoms that they wouldn't normally think of as related
to NHL, but somehow they know that things just aren't right. Still others
may be feeling fine, yet a routine imaging study, blood test, or marrow
biopsy shows a return of disease.
It's likely that your oncologist will order one or more tests if either
you or she notices anything that hints at a return of disease. Many of
these tests, such as a CT scan, bone scan, or gallium scan, will be
familiar from your experiences during your initial diagnosis.
When symptoms or signs of returned disease are noticed by the survivor,
a loved one, or a medical professional, and the return of disease becomes
unquestionably apparent during a subsequent physical examination or imaging
study, it's called a clinical relapse.
If you have symptoms of recurrence many years after successful
treatment, you should consider requesting a re-biopsy of the suspicious
area to determine whether this is a relapse, a second primary cancer, or a
benign side effect of earlier treatment.
Cytogenic relapse is relapse detected by one or more tests on the
cellular level in the absence of physical symptoms.
Various blood tests, for instance, may detect the spread of NHL from the
lymph nodes into the blood stream. Fluorescence in situ hybridization
(FISH) and flow cytometry detect cell surface antigens produced by
cancerous cells. A bone marrow aspiration or biopsy may detect
irregularities in cell appearance or in genetic material that are
associated with relapse.
Very broadly, and only in the context of today's treatments, one can say
that low-grade disease relapses more often than intermediate- or high-grade
disease, and that, for intermediate- and high-grade disease, those who were
diagnosed in the advanced stages of illness are more likely to relapse than
those diagnosed in early stages.
With many new treatments being developed for NHL, however, it's not
wise, correct, or ethical to adhere to generalities without continually
revisiting the progress of research and without noting exceptions. Certain
subtypes of NHL, for example, respond very well to treatment and are less
likely to relapse than others.
For intermediate- and high-grade disease, the longer you remain in
remission, the less likely you are to relapse. As with other cancers, you
may be considered cured once you have been in remission for five years.
Although there is no guarantee that NHL will not re-emerge many years
later, it's far less likely as time passes, and indeed, a recurrence at a
much later date should be fully evaluated, including re-biopsy, for the
possibility of a second primary cancer rather than a relapse of NHL.
For low-grade disease diagnosed at stage III or IV and treated with
protocols available at the time of this writing, both long-term stable
disease and remission for five or more years is likely to be followed by
relapse or disease progression. The exception is low-grade disease treated
with bone marrow transplantation, the results of which are too new to
evaluate for long-term success.
Where does a relapse occur?
The various subtypes of NHL behave differently. Some types may relapse
at the original site of disease; others may relapse at quite different
sites. If you are HIV positive or immune-suppressed, you may experience a
relapse in the central nervous system. Disease that was not originally
found in bone marrow may relapse there, causing pain.
Occasionally a relapse is accompanied by a transition to another grade
of NHL. Usually the transition is from low-grade disease to a higher grade,
but it's also possible for a high-grade NHL to return as a lower grade,
although this is less common.
Sometimes biopsied tissue will reveal two grades of NHL in the same
patient, in the same lymph node, or in two different organs. When this
occurs, usually the treatment is geared to eliminating the higher-grade NHL
because it may become rapidly aggressive.
Occasionally, a relapse of NHL will, upon biopsy, reveal a mixture of
NHL and one of the Hodgkin's lymphomas, or a mixture of B-cell and T-cell
NHL. This may be either a reflection of our still imperfect classification
systems or a true instance of multiple tumor types.
In the last ten or fifteen years, we have benefited by the tremendous
progress made in medical science's ability to detect cancers at much
earlier stages than in the past. Nevertheless, we forget at times that our
sophisticated imaging tools still provide just a glimpse into the body's
complex workings. Consequently, imaging studies sometimes yield equivocal
results that must be qualified with additional testing or even with a
Following some types of chemotherapy, for example, fatty lesions can
form in the liver. These benign lesions may appear upon CT scanning as
liver metastases. Positron emission tomography (PET) scanning can
distinguish these lesions from NHL that has spread to the liver.
At times, nodes will appear much smaller after treatment without fully
disappearing. They may remain the same size for years, and then disappear.
It's thought that these nodes may be scar tissue. Some types of lymphomas
are more likely than others to scar (sclerose); ask your doctor if your
subtype of NHL may exhibit this characteristic.
Odd lesions on the lungs are sometimes seen on imaging after treatment
has ended. If you had radiation therapy targeted to your chest, these
lesions may be fibrotic tissue arising from an immune system reaction to
How your relapse will be treated depends on how your first appearance of
disease was treated. Often, oncologists assume that the drugs you were
given as first-line treatment will not be the best choice for treating
relapse. The thinking is threefold:
- If they were very effective, you would not have relapsed.
- NHL cells can become resistant to drugs, making them ineffective.
- Some drugs are toxic to various organs, and their lifetime dose must be
Upon relapse, it's usually the case that a second drug, a series of
drugs, or radiotherapy will be attempted. Because NHL treatments are
evolving continually, any attempt to describe herein the specific
treatments your doctor might suggest would be quickly outdated.
If you didn't familiarize yourself with clinical trials during your
first experience with NHL, now is a good time to do so. Clinical trials are
a good way to gain access to new treatments before they are made available
to the general public.
Clearly, relapse is an emotional lowland for almost anyone affected by
NHL, including the survivor, the family, friends, and the oncologist.
The emotional issues faced at relapse are different in quality and scope
from those encountered at first diagnosis and endured during treatment.
What follows are some of the reactions that many NHL survivors describe
Fear and terror
Feelings of fear or raw terror may overcome you, even if the odds remain
in your favor. A sense that your options are narrowing may grow stronger,
even if they are not. Thoughts of death that you may have been able to put
aside during and after treatment crowd back in, even if you know that there
are still treatment options open to you. Fear of different, stronger
treatments may emerge.
There may be a sense that you fought the good fight, and now you deserve
peace, contentment, and normalcy. Not only are you not getting these just
rewards, you're getting something that could hardly be worse. You may
wonder why unethical, unkind humans go about happy and healthy. You may
find yourself wishing that certain particularly unpleasant people would get
Anger over life's unfairness, perhaps kept in check or rationalized
during the first round of treatment, may now emerge and may cause you, and
those around you, much discomfort. What psychological adjustments you may
have made to your illness may go out the window, seeming to be a waste of
time. Anger may manifest as rage, irritation, cynicism, or depression.
Many people grieve from the moment of diagnosis. They grieve for lost
health, energy, and diminished opportunities of many kinds, from career
opportunities they had to forego to have treatment to loss of fertility or
Not surprisingly, an expanded sense of grief may emerge upon relapse.
Some people can't help but remember having heard that, for many cancers,
failure of first-line treatment entails a poor prognosis. Although you may
know that this generality does not apply to all of the NHL subtypes, it's
still a frightening thought that makes some people grieve for the life they
The initial diagnosis of NHL and first-line treatment often are
addressed with a can-do attitude that may be difficult to sustain at
relapse, even if your chances of long-term survival are just as good after
an additional therapeutic regimen that achieves a solid remission. There's
something about facing the battle all over again that might make you weary
at the very thought of it. You may feel that the difficult treatment you've
already endured was a waste of time. You may question the quality of your
life. You may contemplate suicide.
Loss of trust
You may lose trust in the medical system in general or in your
oncologist in particular. If a strong faith sustained you during diagnosis
and first-line treatment, you might find yourself questioning this faith
now. You might lose confidence in your own ability to meet physical and
Low-grade disease: one person's story
What follows is a description of Nan's emotions surrounding her
experience with NHL that was initially high-grade, but relapsed years later
as low-grade disease:
Each type of lymphoma has its idiosyncrasies, a different sense of the
particular stakes, and of the nature of the journey. I had high-grade
lymphoma as a teen, and experienced that urgency, that sense of "must
treat or die" that accompanies aggressive diagnosis. I was given three
months to live; treatment was necessarily swift and aggressive. And I got
lucky. Big stakes, harsh treatment, near-death experience, and the gift of
My survivorship experience with low-grade NHL has been entirely different.
Diagnosed in 1986, a nasty test called a lymphangiogram showed that all of
my nodes, from my neck to my knees, were both enlarged and abnormal in
architecture. The horror I felt plunged to the core of my being, as my poor
oncologist, also a friend and colleague, gave me the news. I might look for
six years' survival, he said, and he'd do his best to help me.
The glitch however, was that that "help" was to take the form of
nothing. Nothing to do! How could that be? My precious daughters were only
four and six years old--what good was "maybe six years"? Indeed,
Dr. Saul Rosenberg had discovered that for low-grade, nonsymptomatic NHL,
the best course was watch and wait, which meant "go home, Nan, and
live your life while you wait for the beast to transform into its more
aggressive form so we can take our best shot."
This phrase "watch and wait" really pisses me off. I hate it for
myself and for the patients I work with. Oncologists tend to agree, but
aren't invested enough to actually change the established vernacular. It is
a dangerous phrase. Inherent in those three words is the assumption that
the disease will come back, will transform to a more aggressive cell type,
and will need treatment later. Why would anyone want to assume this?
Haven't we discovered the power of words? Even science has begun to study
support groups and the impact of hope--not only on an individual's quality
of life, but on actual length of life. Where is there hope in telling me
that I am to wait until the predetermined worst happens so that I can then
Let's rewrite the speech, shall we? "Nan, you have low-grade lymphoma,
which is one form of non-Hodgkin's lymphoma. This type of NHL tends to have
a personality of its own, it waxes and wanes, comes and goes, and nobody is
certain at this time what sets it off or puts it back. What has been
documented is that those in your situation fare equally well without
aggressive treatment as with it, sometimes better. There are individuals
your age and stage who have lived for years and years without treatment,
who continue to live well. Others' NHL becomes bulky or perhaps develops
symptoms, at which time we would recommend any number of treatments, from
low-grade chemotherapy to trials with monoclonal antibodies and the like.
There is every reason to believe you can live long and well with this
disease. We must know that wellness is key, and believe that it is just as
likely that your nodes will recede--wane--as it is that they will grow or
wax. My suggestion today is that you take some time to get used to the
diagnosis, then we can explore your options. Here is some reading material,
get acquainted with this disease, it's less scary that way. And at the very
least, let's consider what you can do to bring your body to its optimum
state of wellness, so you are best able to fight the NHL, and to offer you
the most quality of life."
Family and friends
The reactions of friends and family may be completely supportive,
positive, and loving, or particularly inept. Unless they're kept well
informed about your illness and its likely patterns, they may give up on
being sustaining, instead treating you as if you have one foot in the
grave. They may mourn prematurely; they may practice living without you
emotionally. One way to forestall these negative reactions is to inform
them from the beginning that NHL can be treated very successfully at
Employers may begin to lose patience with you at the prospect of yet
more absenteeism. Your children may once again exhibit earlier, less
adaptive behaviors that they had outgrown, such as aggression, bedwetting,
or temper tantrums.
Support groups are an inestimable resource for regaining emotional
footing and a balanced outlook. If you didn't examine options for finding
support during your first experience with NHL, it would be wise to do so
now. It's not an overstatement to say that you'll be overwhelmed by
feelings of hope and energy when you discover how many other people have
gone through what you're experiencing, and came through it in good
Many forms of support are available for cancer survivors in general and
NHL survivors in particular.