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.
