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Spontaneous regression

  

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 About Lymphoma > Spontaneous Regressions

Last update: 10/15/2007

TOPIC SEARCH: PubMed | Web

Spontaneous regressions are the observed decreases in tumor burden, which is relatively common in patients with indolent lymphomas.  

Depending on the source, as many as 20% to 30% of patients will experience regressions at some time in the clinical course of their disease. This observed clinical tendency is also called waxing and waning.

  1. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. 
    N Engl J Med. 1984 Dec 6; 311(23): 1471-5. PMID: 6548796

Notes on Terminology:

Spontaneous regressions and spontaneous remission are sometimes used interchangeably, but these terms can have different meanings to different people:  

Remission is most often defined as the absence of disease activity (stable disease), which is common in indolent lymphomas ... 

... but remission is sometimes  thought of and used to describe being free of observable disease -- or having no evidence of disease (NED).  

... Given this  ambiguity, we propose that
spontaneous regression be used to describe decreases in tumor burden that appear to occur  spontaneously, without treatment. 

The term waxing and waning is also used to describe the uneven course of lymphomas, particularly of the indolent (slow growing) types.  Waxing means progressing, and waning means regressing.   

We propose that
waxing and waning be used to describe transient or short-term fluctuations in the size of lymph nodes that could be accounted for by inflammation and other factors unrelated to the actual number of malignant cells.  You might think of waxing and waning as being similar to daily fluctuations in the stock market that are not related to longer trends.

Finally, how does one distinguish between
waxing and waning and spontaneous regressions?  

It may be that with spontaneous regressions there will be other signals that suggest true improvements in the state of the disease, such as  improving blood counts, decreasing LDH, and observable improvements in how the patient feels and performs.  

also see Remission, Response and Survival terms

Regressions are always welcomed by the patient, but this characteristic of the disease also makes it more difficult for investigators to evaluate new treatments - requiring larger numbers of patient in clinical trials.  

Here are some theories taken from the literature, with some lay-speculation mixed in:

Immune recognition of the tumor cells may produce an immune response against the tumors, which could include the production of antibodies against antigen targets on the tumor, or NK cell direct killing.

Viruses may infect lymphoma cells as they do other lymphocytes, and thus make them more recognizable to other immune cells. This could be the mechanism behind the measles vaccine which is being studied in clinical trials for lymphoma.

Cytokine signals (chemical messages) may induce lymphoma cells to differentiate (mature to a benign form), or induce them to die naturally in a process called apoptosis.

Stress might raise levels of natural steroids and cause temporary regressions. 

Inflammation may account for waxing and waning of lymph nodes, which would mean that both the waxing and waning are not real indications of tumor progression or regression. If inflammation is caused by immune system activity against the tumor, real regression may happen as well for some people.

Hypoxic (low oxygen levels) that form in tumors may cause them to implode when necrotic (dead areas) form in the center. NOTE: It's also possible that low oxygen conditions can cause cells to adapt and become more aggressive or refractory.

Placebo Effect? Stephen Barrett, M.D. - quackwatch.org 

Recovery from illness, whether it follows self-medication, treatment by a scientific practitioner, or treatment by an unscientific practitioner, may lead individuals to conclude that the treatment received was the cause of the return to good health.

Related
Abstracts
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Spontaneous clinical regression in chronic lymphocytic leukaemia.
Br J Haematol. 2002 Feb;116(2):341-5. PMID: 11841436

"Chronic lymphocytic leukaemia (CLL) is a B-cell disorder, which has a median survival of over 10 years from diagnosis for stage A disease. The natural history of stage A disease is generally indolent or only slowly progressive. 

It is less well known that CLL may undergo spontaneous regression. We report a series of 10 such cases (eight stage A and two stage B) followed at our institutions."   - 
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Spontaneous remission of low-grade B-cell non-Hodgkin's lymphoma following withdrawal of methotrexate in a patient with rheumatoid arthritis: case report and review of the literature.
Br J Haematol. 2002 Aug;118(2):567-8. PMID: 12139747 - PubMed
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Comparison of "host cell infiltrates" in patients with follicular lymphoma with and without spontaneous regression. Am J Clin Pathol. 1988 Sep;90(3):257-61. PMID: 2970792 - PubMed
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Follicular lymphomas--a review of treatment modalities. Crit Rev Oncol Hematol. 2000 Jul;35(1):13-32. Review. PMID: 10863149 PubMed abstract
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Clinical significance of natural killing activity in patients with advanced lymphoma.
J Clin Immunol. 1998 Mar;18(2):132-41. PMID: 9533657 PubMed abstract
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Expression of wild-type p53 and Bcl-2 family genes oscillates with recurrent remission and relapse in an unusual case of low-grade lymphoma. Acta Haematol. 2000;103(4):177-85.
PMID: 11014890 PubMed abstract
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Spontaneous reduction of leukemic lymphoma cells possibly by anti-tumor antibody-mediated phagocytosis; a kappa lambda-dual-positive B cell lymphoma.
Leukemia. 2000 Feb;14(2):278-84. PMID: 10673745 - PubMed abstract
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Spontaneous regression of cancer: possible mechanisms. In Vivo. 1998 Nov-Dec;12(6):571-8. Review. PMID: 9891219 - PubMed abstract
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Spontaneous complete regression of high grade non-Hodgkin's lymphoma. Morphologic, immunohistochemical, and gene amplification analyses. Cancer. 1994 Dec 1;74(11):3023-8.
PMID: 7954265 PubMed abstract 
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Spontaneous regression of acquired immune deficiency syndrome-related, high-grade, extranodal non-Hodgkin's lymphoma. Cancer. 1992 Apr 1;69(7):1856-7. PMID: 1551068 PubMed abstract
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Spontaneous regression in non-Hodgkin's lymphoma: clinical and pathogenetic considerations.
Am J Hematol. 1989 Jun;31(2):138-41. Review. PMID: 2660545 PubMed abstract
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Regression of primary high-grade gastric B-cell lymphoma following Helicobacter pylori eradication. Eur J Gastroenterol Hepatol. 2001 Nov;13(11):1375-8. PMID: 11692066 PubMed abstract My note: Not really a spontaneous cause for regression.
 
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