LYMPHOMA
The fifth most common cancer in the US
Malignant lymphomas are a
heterogeneous group of disorders that arise in the
reticuloendothelial and lymphatic systems. Although there are some
similarities among the lymphomas, these diseases display a wide
variety of pathological and clinical characteristics.
Malignant lymphomas are the fifth most common cancer in the US.
Because they tend to occur in younger individuals, they account
for more years of potential life lost than most other adult
cancers.
Cancers of the lymph system (Hodgkin’s and non-Hodgkin’s
lymphoma) have unique etiologies and behaviors that place this
malignancy in a different immune category than most solid tumors.
Because this class of malignancy is characterized by some type of
immune cell proliferation, treatments which boost immunity
might also stimulate the growth of cancer cells. This is a
theoretical concern, but a valid one nevertheless. Even so, it
appears that nutritional and botanical medicines have an important
role to play in the treatment of lymphoma.
Common Characteristics of Hodgkin’s and non-Hodgkin’s Lymphoma
Lymphomas are characterized by excessive multiplication of
cells of the reticuloendothelial (RES) and lymphatic system.
Hodgkin’s Disease, first identified by Thomas Hodgkin in 1666,
is a malignancy characterized by disseminated growth of tumor
cells primarily involving the lymph node and bone marrow.
Reed-Sternberg (RS) cells are considered the malignant cell.
There are subtypes of Hodgkin’s disease. Those with smaller
numbers of RS cells tend to be indolent and slowly progressive.
Higher numbers of RS cells are associated with aggressive disease.
The mortality rate for Hodgkin’s disease is dropping more rapidly
than for any other cancer, and Hodgkin’s disease represents one of
modern medicine’s most successful cancer treatments. More than 50%
of patients are alive at 10-years, all stages considered. By
current conventional cancer treatment standards, this is highly
successful.
Asymptomatic enlargement of cervical (neck) or
mediastinal (chest) lymph nodes may be the only presenting
feature, although a number of benign conditions have similar
presentation. With advancing disease, anemia, weight loss, night
sweats, cachexia (see catabolism) and progressive decline of
immunity may ensue. Death is usually due to sepsis or infection.
Non-Hodgkin’s Lymphoma (NHL) is characterized
by proliferative growth of lymphoid cells in sites of the immune
system including lymph nodes, spleen, bone marrow, liver and GI
tract. There are a wide variety of features among ten subtypes of
non-Hodgkin’s lymphoma (NHL), and the behavior of the disease,
including prognosis, is highly variable. NHL tends to be
multicentric with an early tendency to spread widely before
diagnosis.
The clinical manifestation of fever, chills and
weight loss suggests a possible infectious etiology in all types
of lymphoma. Studies have found an association with the
Epstein-Barr virus (EBV) in both Hodgkin’s and NHL, though this is
clearly not the sole causative agent in 80% of cases. In NHL, the
incidence of disease rises in immunocompromised patients (e.g.,
patients with HIV) and in those with hyperfunctioning immune
systems (e.g., Sjogren’s). Viruses are known to cause some types
of lymphoma. Burkitt’s lymphoma is associated with EBV infection,
and an aggressive T-cell leukemia/lymphoma is associated with
herpes virus type I (HTLV-1).
Metastasis is common in NHL and is often
advanced upon diagnosis. Deposition of fibrin occurs in NHL
lymphomas, as in solid tumors.
Laboratory Evaluation and Monitoring
Diagnosis of lymphoma is based on microscopic characteristics
of a surgically-removed lymph node. There are no characteristic
blood changes or other laboratory tests useful for diagnosis, but
laboratory tests can be used by the physician to monitor disease
progression and success of treatment once a diagnosis is
established.
There are also no characteristic findings in Hodgkin’s disease.
The red blood cell sedimentation rate (ESR) correlates well
with disease activity and can be used to follow the disease
process. Elevated alkaline phosphatase suggests liver or
bone metastasis but this is less reliable in younger patients.
Elevated serum copper and ceruloplasmin have been
reported in active disease. HD patients frequently demonstrate
defects in delayed hypersensitivity reactions. (e.g.,
testing negative for TB even in the presence of active tubercular
disease).
In NHL, a Coombs’-positive autoimmune hemolytic anemia
occurs more commonly than in HD. Immune cell abnormalities may
involve B-cells, T-cells or both cell lines.
Immunophenotyping has shown that 80 to 85% of the tumor tissue in
NHL derives from the B-cell line, 15% from T-cells, and less than
5% from monocyte-macrophages. NK cell activity is
correlated with disease status in lymphomas, and a sudden
decreased NK cell activity has been shown to precede relapse.
Holistic Diagnosis & Treatment Considerations
The actual diagnosis of lymphoma requires excisional biopsy.
Immune system dysfunction, manifesting as either hypoimmune or
hyperimmune, is highly suggestive of an infectious etiology.
Therefore, additional search for a causative agent should be
undertaken. Work-up might include examination of gut microflora,
blood studies for EBV, HTLV-I, and possibly other viruses, and
immune function tests, especially NK cell activity.
Treatment strategy for lymphoma should be targeted to the
individual. Generalized immune-upregulating therapies could
theoretically accelerate cell multiplication and should be used
with care. By targeting treatment to the patient’s particular
immune dysfunction and monitoring patient response, such problems
can likely be circumvented.
Botanical and Nutritional Considerations in Lymphoma
All botanical therapies used for the immune system can be
considered. Again, due to the possibility of accelerating immune
cell growth (the cells that are cancerous), these therapies should
be selected with care and based upon the individual’s immune
status as determined by laboratory studies. Antimicrobial
treatment should be initiated whenever a pathogenic virus,
bacteria or parasite is found. In addition, there are botanical
and nutritional treatments that are specific to treatment of the
lymphomas.
Characteristics of the Lymphomas with Suggestions for Related
Treatment Strategies
Hodgkin’s (HD)
1.) RS cells thought to arise from monocyte/macrophage cells
2.) low NK cell activity
3.) progressive T and B-cell decline (number and function)
4.) altered lymphocyte count
5.) delayed hypersensitivity reaction
Treatment Strategy
1.) Induce differentiation of monocytes and macrophages
2.) Stimulate NK cell activity
3.) Stimulate cellular and humoral immunity
4.) Stimulate or suppress lymphocyte proliferation as indicated
5.) Stimulate delayed hypersensitivity
non-Hodgkin’s (NHL)
1.) 80-85% of NHL cells arise from B-cells; 15 % from T-cells
2.) low NK cell activity
Treatment Strategy
1.) If B-cell derived:
a.) Induce B-cell differentiation
b.) Do NOT stimulate B-cell proliferation
2.) Stimulate NK cell activity
Botanical Materia Medica
by action
Interleukin-2 stimulators ( IL-2)
Aloe vera
Angelica sinensis
Ganoderma lucidum
Panax ginseng
Cordyceps sinensis
Interferon stimulators ( IFN)
Aloe vera
Astragalus membranaceus
Ganoderma lucidum
Glycyrrhiza sp.
Panax ginseng
Delayed hypersensitivity
Codonopsis pilosula
Rheum palmatum
T and B-lymphocyte activity stimulators
(expand and activate T-helper lymphs and B-cells)
Althea officinalis
Astragalus membranaceus
Echinacea sp.
Eleutherococcus senticosus
Eupatorium perfoliatum
Plantago sp.
Symphytum sp.
T-cell activity
Allium sativum
NK-activity
all that stimulate IL-2 and IFN plus:
Allium sativum
Nutritional Considerations in Lymphoma
Vitamin A
Vitamin A induces differentiation in leukemic and
lymphomic cells. A vitamin-A analog, Vesanoid, is approved for use
in promyelocytic leukemia, but it may be of value in other
leukemias and lymphomas. Dose: 100,000-300,000IU water soluable
vitamin A per day. At this high dose it is important to conduct
monthly blood tests to guard against vitamin A toxicity.
Vitamin D3
Vitamin D3 and its analogs can induce leukemia and lymphoma
cells to differentiate into normal cells. The effects are more
pronounced when combined with vitamin A .
Additional support may include
DHEA, turmeric, soy (genisteins). Consult an holistic
physician for precise recommendations and dosages.
DR. MYATT’S COMMENT
Lymphomas (Hodgkin’s and non-Hodgkin’s)
represent a large class of related, but sometimes very different,
immune cell cancers. I have been deliberately vague in the dosage
and specific recommendations because, unlike most solid tissue
cancers which respond to immune-cell stimulation, lymphomas may
be made worse by such stimulation. (Again, theoretical but
important to consider). Laboratory tests can help guide the
physician in knowing exactly which conventional and holistic
remedies to prescribe and can also verify the success of such
treatment. It is important to work with an holistic physician
when implementing natural remedies for the treatment of lymphoma.
I am available for telephone consultations.
Botanical Materia Medica for Lymphoproliferative Disorders
Allium sativum (Liliaceae)- Garlic
See Laboratory Evaluation of Immune Dysfunction Materia
Medica elsewhere in these conference notes.
Althea officinalis (Malvacea)- Marsh mallow
Marsh mallow contains starch, mucilage, pectin, flavonoids,
sucrose, phenolic acids and asparagine. It is considered an
important demulcent for respiratory, urinary and skin
inflammations. The polysaccharide-rich mucilage stimulates T and
B-cell activity and IL-1 and IFN production in vitro(1).
Astragalus membranaceus (Leguminosae)-
Astragalus, Milk Vetch, Huang QI See Laboratory Evaluation
of Immune Dysfunction Materia Medica elsewhere in these
conference notes.
Aloe vera (Liliaceae)- Aloes
See Laboratory Evaluation of Immune Dysfunction Materia
Medica elsewhere in these conference notes.
Angelica sinensis (Umbelliferae)-Angelica
Angelica contains volatile oils andcoumarinss. It increases
production of IL-2 in vitro and TNF cytotoxicity in mice (2,3).
Codonopsis pilosula (Campanulaceae) Codonopsis, Dang
Shen
Triterpinoid saponins, alkaloid (perlolyrin),
andpolysaccharidess are among the constituents found in Codonopsis.
In Chinese medicine, Codonopsis is considered to tone the qi and
quiet “false fire.” In patients undergoing radiation treatment,
Codonopsis increased the delayed hypersensitivity reaction but did
not effect leukocyte count. Plasma IgM was slightly increased
(4,5).
Cordyceps sinesis - dong
chong xia cao
Cordyceps increased NK activity
in vitro and in vivo in mice. An ethanol extract increased human
NK activity ex vivo. Water extracts increase proliferation of
spleen lymphocytes and IL-2 production (6,7,8).
Echinacea sp. (Compositae)- purple cone
flower
See Laboratory Evaluation of Immune Dysfunction Materia
Medica elsewhere in these conference notes.
Eleutherococcus senticosus (Araliaceae)-
Siberian ginseng
See Laboratory Evaluation of Immune Dysfunction Materia
Medica elsewhere in these conference notes.
Eupatorium sp. (Compositae)- Boneset, Gravel
root, hemp agrimony
Polysaccharides in multiple species of Eupatorium stimulate T
and B-cell activity, IL-1 and IFN production and macrophage
phagocytosis in vitro ( 9).
Ganoderma lucidum - ling zhi
Ganoderma increased IL-2 in mice in an orally-administered
form. Purified fractions increased peripheral lymphocytes in
humans. this effect is believed due to stimulation of
T-lymphocytes and production of IL-2 and IFN-gamma (10,11).
Glycyrrhiza sp. (Leguminaceae)- Licorice
Glycyrrhizic acid is a principal constituent in licorice and is
thought to be the primary active ingredient. Licorice exerts
antiinflammatory activity by inhibiting the enzyme that catalyzes
cortisol to its inactive metabolites (12,13). Excess cortisol
inhibits growth of lymphoma and leukemia cells by effecting
glucocorticoid receptors on the tumor cell membranes. (Cortisone
and prednisone are used chemotherapeutically in lymphoma). In
spite of the cortisol-enhancing effect, licorice stimulates NK
cell activity and induces IFN production (14).
Panax ginseng (Araliaceae)-Chinese or Korean
ginseng
See Laboratory Evaluation of Immune Dysfunction Materia
Medica elsewhere in these conference notes.
Plantago sp.(Plantaginaceae)-Psyllium, flea
seed, ispaghula (Hindi)
Plantago is well known for it’s mucilaginous constituent that
acts as a demulcent and bulk laxative with antidiarrheal action.
Polysaccharide-rich mucilages stimulate T and B-cell activity,
IL-1 and IFN production and macrophage phagocytosis in vitro (9).
Rheum palmatum (Polygonaceae)-Chinese rhubarb
Rheum contains the anthroquinones rhein, emodin, and aloe-emodin,
flavonoids (catechin), phenolic acids, tannins and calcium
oxalate. Large doses of the rhizome are strongly laxative. Oral
administration increase delayed hypersensitivity reactions and
increased proliferation response of spleen cells to mitogen in
mice (15).
Symphytum sp. (Boraginaceae)-Comfrey,
knitbone
Comfrey contains allantoin, mucilage, triterpenoids, phenolic
acids, tannins and pyrrolizidine alkaloids. Allantoin is a cell
proliferant when used topically. The phenolic acids possess
significant antiinflammatory action. Pyrrolizidine alkaloids in
isolated form are toxic to the liver.Whether this is true when the
plant is used in whole form is questionable, since this substance
is present in small amounts in the roots. Aerial parts are
considered safe.
Polysaccharide-rich mucilages stimulate T and B-cell activity,
IL-1 and IFN production and macrophage phagocytosis in vitro (9).
References
1.) Boring CC, Squires TS, Tong T, et al.: Cancer Statistics,
1994. CA Cancer J Clin 1994: 44:7-26.
2.) Devessa SS, Silverman DT, Young JL Jr., et al.: Cancer
incidence and mortality trends among whites in the United States,
1947-1984. J Nat Cancer Inst. 1987;79:701-770.
3.) Beers, Mark M.D., Berkow, Robert, M.D., editors: The Merck
Manual of Diagnosis and Therapy, Merck Research laboratories,
1999, p. 955.
4.) Ibid. p.955.
5.) Murphey, Gerald, M.D., et al.: American Cancer Society
Textbook of Clinical Oncology, American Cancer Society, 1995, p.
460.
6.) Ibid. p. 456.
7.) Ibid p. 456
8.) Ibid p. 456
9.) Ibid p. 456
10.) Nagy JA, Brown LF, Senger DR, et al.: Pathogenesis of
tumor cell stroma generation: a critical role for leaky blood
vessels and fibrin deposition. Biochem biophys Acta 1989;
948(3):305-26.
11.) Boik, John: Cancer and Natural Medicine, Oregon Medical
Press, 1995, p.62.
12.) Beers, Mark M.D., Berkow, Robert, M.D., editors: The Merck
Manual of Diagnosis and Therapy, Merck Research laboratories,
1999, p. 957.
13.) Ibid. p. 595.
Botanical Materia Medica References
1.) Wagner H: “Immunostimulants from medicinal plants.”
Advances in Chinese medicinal materials research Chang HM,
Yeung W, Tso W, Koo A editors: Singapore, World Scientific, 1985.
2.) Weng XC, Zhang P, Gong SS, et al.: Effect of
immunomodulating agents on murine IL-2 production. Immunology
Invest 1987; 16 (2):79-86.
3.) Haranaka K, Satomi N, Sakurai A, et al.: Antitumor
activities and tumor necrosis factor producibility of traditional
Chinese medicines and crude drugs. Cancer Immunol
1985b;20(1):1-5.
4.) Zeng XL, Li XA, Zhang BY: Immunological and hematopoeitic
effects of Codonopsis pilosula on cancer patients during
radiotherapy. Chung Hua Min Kuo Wei Sheng Wu Chi Mien I Hsueh
Tsa Chih 1992: 12 (10): 607-8.
5.) Chang HM, But PPH: Pharmacology and Applications of
Chinese MateriaMmedica Vol. 1 Teaneck, NJ: World Scientific
Publishing Company, 1986.
6.) Xu RH, Peng XE, Chen GZ, et al.: Effects of Cordyceps
sinensis on natural killer activity and colony formation of B16
melanoma. Chin Med J (Eng) 1992;105(2):97-101.
7.) Liu C, Lu S, Ji MR: Effects of cordyceps sinensis on in
vitro natural killer cells. Chung Kuo Chung Hsi I Chieh Ho Tsa
Chih 1992a;12(5):267-9,259.
8.) Cheng Q: Effects of cordyceps sinensis on cellular immunity
in rats with chronic renal insufficiency. Chung Hua I Hsueh
Tsa Chih 1992;72(1):27-9.
9.) Wagner H: “Immunostimulants from medicinal plants.”
Advances in Chinese medicinal materials research Chang HM,
Yeung W, Tso W, Koo A editors: Singapore, World Scientific, 1985.
10.) Zhang LX, Mong H, Zhou XB: Effect of Japanese Ganoderma
lucidum (GL) planted in Japan on the production of interleukin-2
from murine splenocytes. Chung Kuo Chung Hsi I Chieh Ho Tsa
Chih 1993;13(10):613-5.
11.) Haak-Frendscho M, Lino K, Sone T, et al.: Ling-G 8: A
novel T cell mitogen induces cytokine production and upregulation
of ICAM-1 expression.. Cell Immunol 1993;150(1):101-113.
12.) Baker ME: Licorice and enzymes other than
11B-hydroxysteroid dehydrogenase: an Evolutionary perspective.
Steroids 1994;59(2):136-41.
13.) Chang M: Anticancer medicinal Herbs. Hunan Changha, China:
Hunan Science and Technology Press, 1992.
14.) Suzuki F, Schmitt A, Utsunomiya T, et al.: Stimulations of
host resistance against tumors by glycyrrhizin, an active
component of licorice roots. In Vivo, 1992; 6: 589-96.
15.) Ma L: Experimental study on the immunomodulatory effects
of rheubarb. Chung Hsi I Chieh Ho Tsa Chih 1991;
11(7): 418-9, 390.
Nutritional Materia Medica References
1.) The in-vitro effects of all-trans retinoic acid and
hematopoeitic growth factorson the clonal growth and self-renewal
of blast cells in acute promyelogenous leukemia. Leuk Res
(ENGLAND) April 1997; 21 (4):285-94.
2.) All-trans retinoic acid in hematological malignancies, an
update. GER (GruppoEmatologicoRetinoidi) Haematologica
(ITALY) Jan-Feb 1997; 82(1): 106-21.
3.) All-trans retinoic acid (Tretinoin). Gan To Kagaku Ryoho
(JAPAN) Apr 1997; 24(6): 741-6.
5.) Induction of differentiation in murine erythroleukemia
cells by 1,alpha, 25 dihydroxy vitamin D3. Can Lett 1995; Apr 14.
90(2):225-30.
6.) 1,25(OH)2-16ene-vitamin D3 is a potent antileukemic agent
with low potential to cause hypercalcemia. Leuk Res June
1994;18(6):453-63.
7.) All-trans and 9-cis retinoic acid enhance 1,25
dihydroxyvitamin D3-induced monocytic differentiation of U937
cells. Leuk Res (ENGLAND) Aug 1996;20(8):665-76.
8.) Combination of a potent 20-epi-vitamin D3 analog (KH 1060)
with 9-cis-retinoic acid irreversibly inhibits clonal growth,
decreases bcl-2 expression, and induces apoptosis in HL-60
leukemic cells. Cancer Research (USA) 1996;56/15:3570-76.
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