Wichtig: Wenn Sie bestrahlt werden, sollten Sie keine Soja-Extrakte einnehmen! Diese können möglicherweise die Effektivität einer Strahlentherapie mindern. Gegen eine ergänzende Anwendung vor oder nach einer Strahlentherapie bestehen jedoch keine Einwände (rechtzeitig ein paar Tage vorher absetzen!).

 

Leukemia and Lymphoma (Hodgkin's and Non-Hodgkin's Disease)

Updated: 07/08/2004

§                     Leukemia

§                     Hodgkin's Lymphoma

§                     Non-Hodgkin's Lymphoma

§                     Signal Transduction Pathway Inhibition

§                     Adjuvant Treatments

§                     Conclusion

§                     Summary

Leukemias are cancers of the blood-forming organs, and lymphomas are cancers of the lymphatic tissues. In general, leukemias and lymphomas respond well to the conventional treatment methods of chemotherapy and radiation therapy. Because there are many different types of these cancers, treatment is based on the specific diagnosis of the disease.

LEUKEMIA

In the United States, more than 30,000 new cases of leukemia will be diagnosed in the coming year, and adult onset of the disease will account for 90% of these cases. Leukemia is not a single disease but a group of related diseases. There are no specific symptoms for leukemias; instead, symptoms are more generalized and include fatigue, weakness, unexplained weight loss, and pain. Most cases of leukemia are found during routine laboratory tests such as a complete blood count (CBC with differential).

Once the initial diagnosis of leukemia is made, further testing includes bone marrow aspiration, lumbar puncture, and excisional biopsies to determine the specific type of leukemia. When leukemias are detected, they are not classified by stages because they are systemic diseases and other organs such as the spleen, lymph nodes, liver, and central nervous system are already involved.

Leukemias are classified into acute and chronic forms. Cancerous cells rapidly reproduce and accumulate in both forms of the disease, crowding out normal white blood cells. The difference between the two forms of leukemia is that, in the acute form, bone marrow cells do not reach maturity and immature cells accumulate. In the chronic form, the cells appear mature but are abnormal and live longer than normal white cells. If left untreated, the majority of patients with an acute form of the disease have a life expectancy of 1 year.

Leukemias are further classified according to the type of affected bone marrow cells. The cancer is myelogenous if the involved blood cells are granulocytes or monocytes. The cancer is lymphocytic if the affected cells are lymphocytes. Leukemias are divided into four main types: acute myelogenous (AML), chronic myelogenous (CML), acute lymphocytic (ALL), and chronic lymphocytic (CLL). There are also several subtypes of these diseases based upon the French-American-British (FAB) classification system for acute leukemias. Prognosis and treatment are based on the diagnosis of the type and subtype of the disease.

Leukemias respond well to chemotherapy and radiation therapy, and these treatment methods are often used in combination. The treatment of leukemia involves the use of a combination of cancer medications given over a period of time. As a general rule, AML will be treated with high doses of chemotherapy agents over a short period of time, whereas ALL is treated with lower doses of chemotherapy over a longer period of time.

Chemotherapy agents attack rapidly dividing cells; however, they also interfere with the production of white blood cells, thereby exposing the patient to the risk of infection. Medications known as growth factors increase white blood cell counts and are often given in combination with chemotherapy. Interferons (IFN) are a group of naturally occurring biologic response modifiers that are sometimes used in the treatment of chronic leukemias (Aviles 1997). The most commonly used of these substances is interferon-alpha.

Interferon reduces the growth of cancerous cells, inhibits their replication, and enhances the immune system's response to the cancer. Interferon appears to be particularly useful when it is used as a maintenance therapy in patients with minimal residual disease (post-remission) or complete remission. In addition, all-trans retinoic acid (a vitamin A analogue), when used in combination with Interferon, may be useful in prolonging the lives of patients with promyelocytic leukemia and other forms of the disease (Zheng et al. 1996; Sacchi et al. 1997). A cautionary note to the use of this therapy is that the patient may be at risk for thrombosis (blood clots). However, heparin therapy or the use of certain nutrients may reduce this risk .

Other therapies for the treatment of leukemias include stem-cell therapy. Stem-cell therapy involves removing stem cells from the patient either by bone marrow aspiration or by a procedure called apheresis (also called peripheral blood stem-cell (PBSC) transplant), when the cells are removed from the peripheral blood system. Stem cells may be obtained from the patient or from a donor who is a close tissue match to the patient. In this therapy, high doses of chemotherapy and radiation therapy destroy the patient's bone marrow, and the collected stem cells are then transplanted into the patient to restore normal blood cell production. This type of therapy is still in the experimental stage. As a result, it is very expensive and may not be covered by insurance.

HODGKIN'S LYMPHOMA

Hodgkin's lymphoma is a cancer of the lymph nodes. The American Cancer Society estimated that over 7400 new cases of the disease would be diagnosed in 2001. However, Hodgkin's disease has an overall cure rate of 75% in newly diagnosed cases. Slightly more than half of all newly diagnosed cases will occur in men.

Although it may affect any lymph tissue, Hodgkin's disease most commonly affects the supraclavicular, high cervical, or mediastinal nodes. Some patients exhibit no symptoms of the disease, although others may have fever, night sweats, or weight loss, among other symptoms. Most patients have one or more slow-growing, enlarged lymph nodes, but because swollen lymph nodes are more often associated with infections, patients often ignore this symptom. It is important to have any lymph node more than 1 cm (0.39 inches) in size evaluated by a physician, particularly if the node enlargement is not associated with infection.

If Hodgkin's disease is suspected, the patient may undergo magnetic resonance imaging (MRI) or computed tomography (CT) to determine the location(s) of enlarged nodes inside the body and to detect any abnormalities of the spleen or other organs that may be associated with the disease. Diagnosis is confirmed by any one of a number of biopsy techniques, including fine needle aspiration, excisional biopsy, or incisional biopsy. A bone marrow aspiration may also be used to stage the disease.

Once the diagnosis is made, it is important to stage the disease. Staging determines the disease's extent of involvement. This information is used to plan a treatment program and will affect the survival rate. Clinical staging consists of a thorough patient history and physical examination, x-rays, and laboratory tests. Other diagnostic tools for staging include gallium scans and lymphangiograms (a type of x-ray). Some patients require pathological examination that involves a surgical procedure called a laparotomy (sometimes referred to as a staging laparotomy). The current staging system for Hodgkin's disease is the Ann Arbor Staging Classification system. Four stages (I, II, III, IV) of the disease are recognized, based upon the degree of involvement. Stage I disease is the least serious and Stage IV the most serious.

Hodgkin's lymphoma is treated using a combination of chemotherapy agents. There are two common chemotherapy combinations: mechlorethamine (Mustargen), vincristine (Oncovin), prednisone (Deltasone, Meticorten), and procarbazine (Matulane) or Adriamycin, bleomycin (Blenoxane), and dacarbazine (DTIC). The type of chemotherapy used will depend upon a number of factors, including the stage of the disease and the patient's age.

Radiation therapy is often used in combination with chemotherapy. Depending on the severity of the disease, radiation may involve the use of a focused beam of radiation or total nodal irradiation. As with all types of lymphomas, bone marrow transplantation or peripheral blood stem-cell transplantation may be considered in patients who do not respond to chemotherapy or radiation therapy.

NON-HODGKIN'S LYMPHOMA

The American Cancer Society estimated that nearly 56,200 new cases of non-Hodgkin's lymphoma (NHL) would be diagnosed in 2001. NHL is the fifth most common type of cancer in the United States. The disease is difficult to treat, with an average 1-year survival rate of 70% and a 5-year survival rate of 51%. Approximately 90% of all non-Hodgkin's lymphomas are diagnosed in adults. The average age at diagnosis is in the early 40s, and the disease is slightly more common in men than in women. The risk for the disease increases throughout life. Other potential risk factors for the disease may include adult-onset diabetes of long duration and a history of previous cancers, according to a British study (Cerhan et al. 1997). Survival rates for non-Hodgkin's lymphoma are variable, depending on the type of cell involved and the stage of the disease.

Non-Hodgkin's lymphomas are cancers that also affect the lymphatic system, particularly the lymphocytes--the cells responsible for maintaining the body's immune system. There are two major types of lymphocytes: B-cells and T-cells. B-cells are more common and are involved in approximately 85% of all non-Hodgkin's lymphomas.

Generalized symptoms of the disease include unexplained weight loss, fever, profuse sweating, and severe itchiness. The disease may affect the lymph nodes close to the body's surface (e.g., in the neck, groin, or underarm). These nodes become swollen and are usually noticeable to the patient. If lymph nodes in the abdomen are affected, the patient may experience abdominal swelling resulting from accumulating fluid or tumor growth. If lymph nodes near the intestines are affected, the patient may have difficulty with the passage of stools. When the lymphoma originates in the thymus, the growth of the tumor may block the trachea or the superior vena cava may become compressed, resulting in a life-threatening condition known as superior vena cava (SVC) syndrome.

The disease is diagnosed by fine needle aspiration, incisional biopsy, or excisional biopsy. Other techniques used to assist in the diagnosis include x-rays, CT scans, and bone marrow aspiration. Because there are a number of different types of malignancies in non-Hodgkin's lymphomas, the types are classified according to two systems. The Working Formulation classifies these lymphomas based on prognosis: The categories are low, intermediate, and high-grade. The Revised European American Lymphoma (REAL) system divides NHL into types according to clinical behavior. The categories are indolent, aggressive, and highly aggressive. High-grade and highly aggressive tumors are the most difficult to treat.

Treatment for non-Hodgkin's lymphoma depends on the type of lymphoma (e.g., indolent or aggressive), the stage of the disease, the age of the patient, and the patient's overall health. As in Hodgkin's lymphomas, chemotherapy and radiation therapy are used to treat the disease. Bone marrow transplantation may be considered for patients who do not benefit from other forms of therapy. In one study, Interferon was found to be an effective treatment for low-grade lymphomas; however, intermediate- and high-grade tumors did not respond as well. Studies of B-cell non-Hodgkin's lymphomas also indicated that Interferon-gamma and -alpha might be useful in the treatment of certain types of the disease (Tourani et al. 1989; McLaughlin 1996).

SIGNAL TRANSDUCTION PATHWAY INHIBITION--A NEW TREATMENTAPPROACH

Information has emerged offering an entirely new approach to the treatment of leukemias and lymphomas. Early in the progression of these diseases, many, although not all, have been found to express certain cytokine chemical messengers or signal transduction pathways previously thought only to be expressed in human solid tumors as well as certain inflammatory and immunosuppressive cytokines. The blockade or inhibition of these signal transduction pathways in human solid tumors has yielded dramatic results. One example is the drug Iressa made by AstraZenca. Iressa has produced positive results in certain cancers via a blockade of the epidermal growth factor receptor site (EGFR) found to be over-expressed in many cancers (see the Cancer Adjuvant Therapy protocol for information on natural supplements that have been shown to inhibit certain signal transduction pathways).

Growth, pro-inflammatory, and immunosuppressive cytokines often expressed by leukemias and lymphomas are:

Vascular endothelial growth factor (VEGF) is considered essential for cancer cell survival and angiogenesis (the formation of new blood vessels). High levels of VEGF correlate with shortened survival in chronic lymphocytic leukemia (Ferrajoli et al. 2001).

Basic fibroblast growth factor (bFGF) is a potent mitogen (growth signal) and is essential for angiogenesis. Simultaneous elevations in bFGF and VEGF are an independent predictor of a poor prognosis in non-Hodgkin's lymphoma (Salven et al. 2000).

Hepatocyte growth factor (HGF), also known as a multiple function factor, HGF protects cancer cells from cytotoxic agents, contributes to the development of chemo-resistance, and stimulates hematopoiesis (Skibinski et al. 2001). (Hematopoiesis refers to the formation and development of blood cells occurring primarily in the bone marrow and to a lesser extent the lymph nodes.)

Epidermal growth factor (EGF) is essential to the hyperproliferation of some lymphomas and to epidermal cells (Courville et al. 1999).

Tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a proinflammatory cytokine significantly elevated in all leukemias except for AML and myelodysplastic syndromes (Aguayo et al. 2000).

Interleukin-6 (IL-6) is a pro-inflammatory and immunosuppressive cytokine. Elevations in serum IL-6 correlate with adverse disease features and shortened survival in chronic lymphocytic leukemia (Fayad et al. 2001).

The lymphomas and leukemias that can over-express these cytokines are:

 

 

Vitamins A and D3

Soy Extract

Curcumin

Green Tea

GLA/DHA

Statin Drugs

DHEA

Alpha-Lipoic Acid

Shark Liver Oil

Resveratrol

Monthly Blood Markers

Inhibiting Protein-Tyrosine Kinase with Gleevec

 

Although leukemia and lymphomas respond well to the conventional treatment methods of chemotherapy and radiation therapy, other potentially beneficial treatments are available. Vesanoid, a vitamin A analogue, has been approved for the treatment of promyelocytic leukemia. The medication inhibits cell division and allows cells to reach maturity and function normally. Although Vesanoid is approved in the treatment of only a specific type of leukemia, it may be beneficial in the treatment of other types of leukemia (but probably not CLL) and some types of lymphoma (Kerr et al. 2001). Although vitamin A therapy can help to induce remission in patients with promyelocytic leukemia (Mann et al. 2001), the duration of the response to the medication is short-lived. Additional therapy with Vesanoid is often less effective, suggesting that patients may develop some resistance to the medication.

Vitamins A and D3

Research has demonstrated that drug resistance may be overcome by using vitamin A derivatives (retinoic acid) in combination with other medications, such as vitamin D3 and its analogs (Defacque et al. 1996; Elstner et al. 1996; Nakajima et al. 1996; Miyauchi et al. 1997; Ohno 1997). Patients with other forms of leukemia or lymphoma should consult with their physician regarding the potential benefits of this treatment. If the patient's physician does not recommend Vesanoid for treatment of the disease because the FDA has not approved the medication for their type of cancer, patients can consider water-soluble vitamin A as an alternative.

The recommended dose of vitamin A supplementation is 100,000-300,000 International Units (IU) daily. Monthly blood testing is necessary to monitor vitamin A liver toxicity.

Caution:Prior to considering vitamin A therapy, refer to the symptoms of vitamin A toxicity.

Vitamin D3 and its analogs may induce certain leukemia and lymphoma cancer cells to differentiate into normal cells. If vitamin D3 supplements are used, the typical dose for cancer patients is 4000 IU a day.

Monthly blood tests to monitor serum calcium, kidney function, and liver function are necessary to prevent vitamin D3 toxicity. Although not specifically recommended for patients with chronic lymphocytic leukemia, vitamins A and D3 may be beneficial because of their effects against a wide range of cancer cells.

Soy Extract

A potentially beneficial adjuvant approach for leukemia and lymphoma uses soy extracts with high genistein content. Genistein is an inhibitor of protein tyrosine kinase, the enzyme that cancer cells require in order to replicate. A study conducted to assess the effects of genistein in several types of cancer showed that protein kinase C activity was inhibited, subsequently retarding the growth of cancer cells (Carlo-Stella et al. 1996a; 1996b).

Studies suggest that genistein may also enhance the effects of chemotherapy via a blockade of a number of signal transduction pathways. These are:

Inhibition of the EGF receptor via an interference with the transforming growth factor-alpha (TGF-alpha) pathway (Bhatia et al. 2001)

Suppression of VEGF, considered essential for cancer cell survival (Mukhopadhyay et al. 1995)

Suppression of bFGF, a potent growth cytokine (Hurley et al. 1996)

The blockade or inhibition of these important signal transduction pathways is dose-dependent, that is, more is better.

In patients whose tumor cells have mutant p53 oncogenes, the benefits of soy extracts may be even more significant, since genistein, from soy, has been shown to down-regulate mutant p53 oncogenes. One key to a tumor's response to treatment is the presence or absence of a functional p53 tumor suppressor gene, which produces a protein that cells need to undergo apoptosis (i.e., to die) when damaged. If p53 is functional, cancer cells damaged by radiation or chemotherapy self-destruct. However, if the genetic changes that lead to cancer also inactivate the p53 gene, which appears to occur in about half of all human malignancies, the cancer defies treatment.

The presence of mutant p53 genes is determined by pathologic examination of the cancer cells.

If the test for mutant p53 is positive, then soy extract therapy may be very beneficial. The Foundation realizes that many cancer patients desiring to use soy extracts may not be able to have immunochemistry testing for mutant p53. Patients may wish to consult their physicians to determine if mutant p53 was discovered during diagnosis of their disease.

The most concentrated form of soy extract available is Ultra Soy Extract. The recommended dose for cancer patients is five 700-mg capsules taken 4 times daily.

Curcumin

An extract of the spice turmeric, curcumin is synergistic with the soy isoflavone, genistein, and has a number of cytokine-inhibiting properties, such as the inhibition of angiogenic signals from tissue-like bone marrow, as well as the down-regulation of pro-inflammatory cytokines.

Curcumin has also been shown to:

Inhibit induction of bFGF, a potent mitogen (growth signal) and essential in angiogenesis (Arbiser et al. 1998)

Inhibit induction of hepatocyte growth factor (HGF), a multiple function cytokine. Over-expression of HGF is involved in the development of chemo-resistance, protecting cancer cell DNA, and excessive hematopoiesis (Skibinski et al. 2001).

Increase expression of functional nuclear p53 protein in leukemia cell lines. This increases apoptosis (cell death) (Kuo et al. 1996; Jee et al. 1998; Pan et al. 2001).

Down-regulate the inflammatory cytokine TNF-alpha in bone marrow stromal cells (Xu et al. 1997).

Based on the multiple favorable mechanisms listed above, higher dose curcumin would appear to be useful for cancer patients to take.

Concerning curcumin being taken at the same time as chemotherapy drugs, there are contradictions in the scientific literature. Some studies indicate significant benefit, whereas other studies hint at reduced benefit or even potential toxicity. One study involving curcumin's concomitant use with the chemotherapy drug, Irinotecan, indicated potential toxicity (Michaels et al. 2001). Therefore, Life Extension recommends that curcumin not be taken in combination with this drug. Irinotecan is also known by the names Camptosar and CPT-11.

Chemotherapy drugs are highly toxic. Whether high-dose curcumin is beneficial or detrimental, depends on the type and dose of the chemotherapeutic drug used, the kind of cancer cell being attacked, and the dose of curcumin. Until more definitive information is published, we prefer to err on the side of caution and recommend that chemotherapy patients wait 3 weeks after their last dose of chemotherapy before taking high doses of curcumin. A high-dose of curcumin is 3600 mg taken 3 times a day. This high dose is sometimes consumed for 6-12 months and then reduced.

Green Tea

The primary action of green tea is through its catechin, EGCG, which blocks the induction of vascular endothelial growth factor (VEGF), considered essential in angiogenesis. In vivo studies have shown the following actions on cancer cells (Jung et al. 2001):

A 58% inhibition of tumor growth

A 30% inhibition of microvessel density

Increase tumor cell apoptosis 1.9-fold

Increased endothelial cell apoptosis threefold

Note:It may be more efficacious to take green tea in capsule form rather than as a brewed beverage as a cancer adjuvant therapy. An appropriate dose for VEGF blockade would be 5 capsules of the lightly caffeinated Super Green Tea Extract capsules with each meal. Each capsule provides 100 mg of the critical anticancer polyphenol called epigallocatechin gallate (EGCG). Caffeine has been shown to potentiate tea polyphenols, such as EGCG. Because caffeine can keep some people awake at night, it might be preferable to take 5 decaffeinated Super Green Tea Extract capsules as the evening dose, or use decaffeinated green tea exclusively if hypersensitive to caffeine.

GLA/DHA

The down-regulation of inflammatory cytokines is fundamental to the control and eradication of the disease process. As previously noted, many leukemias and lymphomas over-express the inflammatory cytokines TNF-alpha and IL-6. Essential fatty acids are derived from sources such as fish, primrose, and borage oils. The docosahexaenoic acid (DHA) and gamma-linolenic acid (GLA) portions of these fatty acids have been shown to suppress these dangerous cytokines (Purasiri et al. 1997; De Caterina et al. 2000). Additionally, the use of GLA and DHA has been shown to improve leukemia's response to chemotherapy (Liu et al. 2000).

Statin Drugs

A family of oncogenesknown as rasoften governs the regulation of cancer cell growth. The RAS family is responsible for modulating the regulatory signals that govern the cancer cell cycle and proliferation. A class of drugs known as the statins (used to control cholesterol) has also been found to induce apoptosis (cell death) in cancers that express the rasmutation. Acute myeloid leukemia strongly expresses the H-Rras mutation and has been found to be highly sensitive to one of the newer statins called cerivastatin. Cerivastatin has been found to be at least 10 times more potent at inducing apoptosis in AML than any previous statin drug (Wong et al. 2001).

DHEA

An interesting study (Inserra et al. 1998) showed that the hormone DHEA (dehydroepiandrosterone) favorably modulated the immune dysfunction that occurred during murine leukemia retrovirus infection in old mice. Leukemia is associated with deregulated cytokine production. When leukemic mice were given DHEA supplements, the loss of the cytokines, interleukin-2 and interferon-gamma was prevented (Araghi-Niknam et al. 1997). DHEA also suppressed the excessive production of the dangerous cytokines, interleukin-6 and interleukin-10. This preliminary study indicates DHEA might be effective in treating the immune dysfunction in those leukemia patients with a DHEA deficiency (especially older people).

Caution:DHEA is contraindicated in both men and women with certain hormone-related cancers (please refer to the DHEA Replacement Therapy protocol for complete information on the proper use of DHEA supplements).

Alpha-Lipoic Acid

Alpha-lipoic acid (also known as lipoic acid) is a powerful antioxidant that has demonstrated effects against brain damage, aging, and diabetes. It may also help kill cancerous cells and retard heart disease.

A remarkable study shows how lipoic acid can reverse aging. Researchers at the University of California at Berkeley took liver cells from aging rats and measured how energized they were, how many free radicals were present, and how well the cells could recycle vitamin C. The aged rats were 3 times less active than the young ones. Free radicals were 5 times higher, the generation of energy had plummeted, and the ability to recycle ascorbic acid (vitamin C) was about half. After 2 weeks on lipoic acid, everything was reversed. Ascorbic acid levels rose, free radicals decreased, and energy levels took off. Levels of glutathione, an important antioxidant for the liver, were also protected by lipoic acid (Lykkesfeldt et al. 1998; Hagen et al. 1999).

Dr. Lester Packer is a top authority on antioxidants. Packer and his group at Berkeley published results from a study on lipoic acid and human cancer cells. For the first time they showed that lipoic acid activates an enzyme that kills leukemia cells. The enzyme caspase increased 100% with treatment (Sen et al. 1999). Other research from his laboratory indicates that lipoic acid goads crippled immune cells (such as those of cancer and AIDS patients) into action (Sen et al. 1997). Among his other research projects is one showing that lipoic acid suppresses the "cancer gene," c-fos (Mizuno et al. 1995). Another group, this time at Yale, used lipoic acid and vitamin E succinate with vitamin D3 to make leukemia cells differentiate (become a normal cell as opposed to a cancer cell). Both antioxidants needed vitamin D3 to cause this positive effect (Sokoloski et al. 1997).

A big question is whether a person undergoing chemotherapy should take antioxidants such as lipoic acid. Since generating free radicals is one of the ways chemotherapeutic drugs work, there is concern that taking antioxidants could keep chemotherapy from working. The jury is still out. Some studies show that antioxidants ameliorate the toxic effects of chemotherapy without affecting the ability of the drug to work. Others show that antioxidants reduce the effectiveness of the drugs--at least in cell culture. It may depend on the type of cancer, the drug used, and the dose of antioxidant. People undergoing chemotherapy have reported positive effects, but this is something that should be discussed with an oncologist.

Shark Liver Oil

Alkylglycerols were first isolated from shark liver oil by Dr. Astrid Brohult, a physician in Sweden. Dr. Brohult was treating children with leukemia, with little success. Because white blood cells are produced in the bone marrow, she started to feed bone marrow from calves to the sick children. The result of this bone marrow feeding was a marked improvement in the immune systems and white blood cell counts of the children. Unfortunately, Dr. Brohult was unable to get the children to eat enough bone marrow to sustain these results, so she set out to find the active ingredient in bone marrow and isolate it. With the help of her husband, it was determined that alkylglycerols were responsible for the immune system-enhancing effects. Next, they discovered that alkylglycerols are found in the livers of cold-water sharks, such as the Greenland Shark. The shark in general has attracted attention because cancer occurrence is very rare in sharks. The existence of alkylglycerols in the liver of sharks may be one reason for the natural immunity to cancers.

The biologic effects of shark liver oil include stimulation of blood leukocyte and thrombocyte production (Le Blanc et al. 1995), as well as the activation of macrophage and antitumor activity. Other effects include the ability to protect against radiation damage during radiation therapy for various types of cancer. Alkylglycerols act as a powerful immune system booster against infectious disease and help give nursing animals, including breast-fed babies, protection against infection until their own immune systems can fully develop.

In a study published in the Journal of Cell Physiology (February 1999), Wang et al. studied the cell differentiation-promoting potential of a particular type of alkylglycerol on human colon cancer cells. The scientists wanted to observe the ability of alkylglycerols to change the biological makeup of human colon cancer cells. Alkylglycerols were shown to "... promote a more benign or differentiated phenotype in colon cancer cells." Treatment of the cancer cells with alkyl-glycerols resulted in a reduction of cellular proliferation and a reduced capacity for cellular invasion. In other words, alkylglycerols led to lowered cancer cell reproduction and a reduced ability of the cancer cells to invade healthy cells. The authors concluded that alkylglycerols possess both cancer preventative properties, as well as cancer treatment effects (Wang et al. 1999).

Shark liver oil has been around for 40 years and has been used as both a preventive and therapeutic agent. Not only have alkylglycerols been used to treat leukemia, as in the case of the children in Sweden, but they have also been used to prevent radiation sickness stemming from radiation cancer treatments. Furthermore, the high level of alkylglycerols that exist naturally within any given tumor cell has led scientists to postulate that this may be an apparent attempt of the body to control cell growth. Protein kinase C, an essential step in cancer cell growth, can actually be stopped or inhibited by alkylglycerols. In addition, it has been suggested that alkylglycerols directly act on the macrophages (large immune cells that "gobble up" cancer cells). Overall, alkylglycerols are able to stimulate the macrophage to secrete more than 50 substances concerned directly or indirectly with the immune system. Some of these substances, the interleukins, are powerful immune system fighters that interact with lymphocytes (Pugliese et al. 1998; 1999).

Resveratrol

Resveratrol, a phytoextract found in grapes and red wine may act as a chemotherapeutic agent and inhibit the growth of various leukemia and melanoma cell lines.

Resveratrol is a plant polyphenol found in grapes and red wine. A study published in the journal Blood indicates that resveratrol effectively inhibits acute myelogenous leukemia (AML) cells in vitro through several differentiating properties: blocking activation of nuclear transcription factor NF-kB, inhibiting proliferation, causing S-phase arrest, and inducing apoptosis. This suggests that resveratrol may have a role as a therapeutic agent in the treatment of AML ( Estrov et al.2003)

Asou et al. studied the in vitro activity of resveratrol on acute myeloid leukemia by examining its effect on proliferation and differentiation in various cell lines and in fresh samples of 17 AML patients. Used alone, resveratrol inhibited the growth of all AML . The authors concluded that resveratrol inhibits proliferation and induces differentiation of myeloid leukemia cells ( Asov et al. 2002)

Niles et al. examined the effect of resveratrol on the growth of two human melanoma cell lines. They found it inhibited growth and induced apoptosis in both cell lines with one (A375) being more sensitive. The authors concluded that resveratrol may be effective as either a therapeutic or chemopreventive agent ( Niles et al. 2003.)

From the in vitro studies cited above, an appropriate human dosage cannot be extrapolated.

Monthly Blood Markers

Because all cancer therapies produce individual responses based on factors such as the type of disease, patient's age, and the presence of other diseases, the Foundation recommends monthly blood markers and other diagnostic testing to monitor the benefits of any supplemental therapies. The results of these tests provide critical information to evaluate the effectiveness of nonconventional therapies. If tumor indicators do not decrease after the initiation of any nonconventional therapy, patients should discontinue their use and seek other alternatives immediately.

Inhibiting Protein-Tyrosine Kinase with Gleevec

In the various cancer protocols discussed in this book, references are made to nutrients like curcumin, genistein, and tocopherol succinate that function as protein-tyrosine kinase inhibitors. Because tyrosine kinases induce hyperproliferation of cancer cells, inhibiting these kinases has been shown to slow cancer cell propagation.

A drug called Gleevec (formerly known as STI571) is a protein-tyrosine kinase inhibitor that specifically interferes with the Bcr-Abl tyrosine kinase--the typical chromosomal abnormality seen in chronic myeloid leukemia (CML). Gleevec inhibits proliferation and induces apoptosis in Bcr-Abl cell lines as well as fresh leukemic cells from "Philadelphia chromosome positive" chronic myeloid leukemia (CML). Gleevec may also inhibit growth of other types of cancer cells.

Gleevec (imatinib mesylate) was first made available to patients with chronic myeloid leukemia (CML) in May 2001 after the results of exciting clinical studies were released in Europe. Gleevec is indicated for the treatment of patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.

The effectiveness of Gleevec is continuously being evaluated for efficacy, though it is now an FDA-approved drug. To read about the latest findings on Gleevec, log on to a special website www.gleevec.com.

It is interesting to note that a drug that functions along a similar mechanism as certain dietary supplements was put on the FDA's "fast-track" for approval.

CONCLUSION

Leukemia, Hodgkin's lymphoma, and non-Hodgkin's lymphoma generally respond well to conventional therapies. There are many different types of these diseases; therefore, chemotherapy and radiation therapy are individualized. Patients who do not respond well to chemotherapy and radiation therapy may benefit from other treatments such as bone marrow transplantation or a peripheral blood stem-cell transplant. In addition to conventional treatment, there are a number of alternative therapies available. Patients with certain types of leukemia or lymphoma may derive beneficial effects from Vesanoid, vitamin A, vitamin D3, curcumin, green tea, and soy extracts. It is imperative that patients have regular monitoring of tumor markers (or tumor size) to assess the usefulness of any treatment. Consult your hematologist or oncologist prior to initiating alternative treatments.

SUMMARY

1. Early diagnosis and treatment of leukemias and lymphomas are essential. Symptoms of leukemia and lymphoma are generalized and include fatigue, weight loss, fever, and night sweats. In Hodgkin's and non-Hodgkin's lymphomas, swollen lymph nodes may be present.

2. Diagnosis of the specific disease may include MRI scans, CT scans, and biopsy.

3. Chemotherapy and radiation therapy are usually used in combination to treat these diseases. The actual course of therapy depends on the specific type of disease.

4. Interferon-alpha, a biologic response modifier has been proven effective in the treatment of some leukemias and low-grade lymphomas.

5. Patients who do not respond to chemotherapy and radiation therapy may be considered for peripheral blood stem-cell transplants or bone marrow transplants.

6. Vesanoid, a vitamin A analog, has proven effective in patients with chronic promyelocytic leukemia and may be beneficial for other types of cancers. For chronic myeloid leukemia (CML), ask your doctor about Gleevec.

7. Water-soluble vitamin A may provide a useful alternative to Vesanoid for some cancer patients. The recommended dosage of this vitamin is 100,000-300,000 IU daily.
CAUTION:Monthly blood tests are necessary to avoid vitamin A toxicity.

8. Vitamin D3 and its analogs may induce differentiation of cancer cells into normal cells in certain types of lymphomas and leukemias. A high dose to consider is 4000-6000 IU daily.
CAUTION:Serum calcium, kidney function, and liver function should be monitored monthly to avoid vitamin D toxicity.

9. Curcumin may induce cancer cell death via a blockade of various signal transduction pathways. The recommended daily dosage is four 900-mg capsules 3 times daily with food, taken 2 hours apart from all medications.
CAUTION:Patients with biliary tract obstruction should not take curcumin. High doses of curcumin may induce NSAID-like side effects in the stomach.

10. Green tea extract providing high amounts of epigallocatechin gallate (EGCG) suppress VEGF and other growth factors used by cancer cells to escape regulatory control. An appropriate dose for VEGF blockade would be 5 capsules of the lightly caffeinated Super Green Tea Extract capsules with each meal. Each capsule provides 100 mg of the critical anticancer polyphenol called EGCG. Caffeine has been shown to potentiate tea polyphenols, such as EGCG. Because caffeine can keep some people awake at night, it might be preferable to take 5 decaffeinated Super Green Tea Extract capsules as the evening dose, or use decaffeinated green tea exclusively if hypersensitive to caffeine.

11. Patients who are positive for mutant p53 oncogenes may receive substantial benefits from the use of soy extracts. Soy extract high in genistein, such as Ultra Soy Extract, may inhibit cancer cell growth for a number of types of cancer. Recommended daily dosage of Ultra Soy Extract is five 700-mg 40% isoflavone extract capsules taken four times a day.

12. DHEA replacement therapy may be considered. Blood testing is recommended prior to and during therapy (refer to DHEA Replacement Therapy for more information).

13. Alpha-lipoic acid may help activate the enzyme caspase, which kills leukemia cells. It may also suppress the cancer gene C-FOS. People on a chemotherapeutic regimen should discuss the use of alpha-lipoic acid with their oncologist before taking this supplement. Typical doses of alpha-lipoic acid for cancer patients are 500 mg twice a day.

14. Shark liver oil functions via several mechanisms to suppress cancer growth, enhance immune function, and protect against radiation damage. We recommend five or six 1000-mg capsules (containing 200 mg of alkylglycerols each) daily for a period not to exceed 30 days.
CAUTION:At no time should the maximum recommended dose of shark liver oil be exceeded. In the case of chronic use, more than 30 consecutive days, a possible, albeit rare, side effect known as thrombocythemia (excess thrombocytes) can occur, leading to a tendency for the blood to clot. This condition is easily diagnosed with a blood test and reversed with lower dosages, the addition of a low-dose aspirin (81 mg daily), or omega-3 fatty acid supplementation. Consult with your physician if throm-bocythemia is a consideration or if you are using shark liver oil for the treatment of serious disease states. Other than the rare instance of blood clotting at chronic high doses, the alkylglycerols found in shark oil are remarkably non-toxic.

15. GLA/DHA may be taken for the suppression of inflammatory cytokines. Super GLA/DHA is derived from borage oil and marine lipid concentrate. The suggested dose is 6 softgels daily.

16. Resveratrol has been shown to act as a chemotherapeutic agent in vitro on certain leukemia cell lines. Although as a therapeutic agent, a dosage has not been established, 1 20-mg capsule daily of resveratrol provides multiple health benefits.

Note:At this juncture, the hormone melatonin is not recommended in the treatment of lymphoma and leukemia. Patients should avoid the use of this product until more information is available. If patients do choose to use melatonin, monthly blood testing for tumor markers should be closely monitored to determine if melatonin is promoting leukemic or lymphatic cell proliferation.

FOR MORE INFORMATION

Contact the American Cancer Society, (800) ACS-2345.

PRODUCT AVAILABILITY

Water-soluble vitamin A liquid, vitamin D3 capsules, vitamin C, alpha-lipoic acid, Ultra Soy Extract, curcumin, green tea extract, Super GLA/DHA, DHEA, Resveratrol, and shark liver oil are available by telephoning 0031-485-530860 or by ordering online. Vesanoid, Gleevec and statins are prescription drugs and should be prescribed by your oncologist or hematologist.

STAYING INFORMED

The information published in this protocol is only as current as the day the manuscript was sent to the printer. This protocol raises many issues that are subject to change as new data emerge. Furthermore, cancer is still a disease with unacceptably high mortality rates, and none of our suggested regimens can guarantee a cure.

Before utilizing the cancer protocols in this book, we suggest that you check if any substantive changes have been made to the recommendations described in this protocol. Based on the sheer number of newly published findings, there could be significant alterations to the information you have just read.