Lymphoma Wellness Plan

About Lymphoma

Non-Hodgkin’s Lymphoma (NHL) is the most common type of lymphoma. Hodgkin’s lymphoma is less common, and has a slightly higher cure rate. According to SEER data, in 2011 there were 530,919 people living with NHL in the United States. There has been a 73 percent rise between 1973 and 1991 in NHL with continued increases ever since.

Approximately 2.1 percent of men and women will be diagnosed with non-Hodgkin lymphoma at some point during their lifetime, based on 2008-2010 SEER data, and the 5 year survival rate is 69.3%.

The survival rate for lymphoma has greatly increased in the past 40 years, especially in children. The five-year relative survival rate for NHL patients has risen from 31 percent in Caucasians from 1960 to 1963 to 71.2 percent for all races from 2003 to 2009. In youths under 20, the 5 year survival rate is 84.5%, which is a significant improvement since most youths did not survive 5 years in the 1970s. NHL and Hodgkin lymphoma account for 11% of total cancer diagnoses in children.^[1]

Some of the many subtypes of NHL include: B cell and T cell types , follicular lymphoma, cutaneous lymphoma, marginal zone lymphoma, mantle cell lymphoma, Burkitt’s lymphoma, and lymphoblastic lymphoma . Lymphoplasmacytic lymphoma is a related lymphoma also known as Waldenstrom’s macroglobulinemia.  Other lymphomas may be named for their site of presentation, such as CNS lymphoma.

BREAK UNHEALTHY HABITS

Do not smoke, especially if you have hepatitis C. Heavy smoking doubles the risk of having NHL. Hepatitis C positive individuals who are heavy smokers have a nearly 4-fold higher risk of developing non-Hodgkin lymphoma than non-smokers.^[2]

▼Causes/Contributing Factors

A number of risk factors are known to be associated with lymphoma. Among the most well-established risk factors include:

1. Being of Caucasian race and male gender in the United States.^[3]
2. Aging is a major risk factor for most lymphomas although there are some types that occur more commonly in childhood.
3. Exposure to environmental radiation or being treated with radiation and chemotherapy for other diseases significantly increases the risk of lymphoma.
4. Having HIV or other immune system problems, including other cancers and viral infections such as CMV and EBV, increases the risk.^[4] Infection with hepatitis C nearly doubles the risk of NHL.

Other risk factors include:

1. Obesity and high BMI has been found to be a predictor of worse outcomes specifically for chronic lymphocytic leukemia and small lymphocytic lymphoma (vs. diffuse large B cell lymphoma and follicular lymphoma).^[5]
2. Pesticide and herbicide exposure. Human studies are demonstrating that exposure to pesticides increases the risk of NHL, especially in individuals who work and live on or near farms.^[6][7]  Specifically, diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure.^[8] Glyphosate is a major concern with lymphoma risk.^[9]Additionally, home pesticide use has been associated with a several fold increase in risk for NHL in children.^[10]
3. A number of genetic variants have been associated with risk, particularly when combined with environmental toxin exposure.^[11]
4. Smoking, alcohol use and sedentary lifestyle
5. Autoimmune disease: a number of autoimmune diseases have been associated with a higher risk of NHL, although the absolute risk is still small.^[12]

REDUCE STRESS

Meditation, stress relief, yoga and other modalities to reduce overall stress emotionally and physically have positive effects on lymphoma.^[13]

◄Relevant Diagnostic Testing

A biopsy of the swollen lymph node (s) is recommended and is often preceded by imaging of the body part affected, which can include x-ray, ultrasound, positron emission tomography (PET) computed tomography (CT) or MRI. Once the disease has been detected, other testing of the cancer cells includes cytogenetics and flow cytometry, as well as PET/CT.

Blood testing assesses white and red blood cells (RBC, CBC) and liver function are also routinely part of the diagnosis and monitoring of lymphomas

STAY ACTIVE

Exercise is a well-established way to prevent cancer development, including lymphoma. One study found that women who sat for 6 hours a day had a 28% higher risk of NHL than those who sat for 3 hours per day.^[14]

◄Dietary Action Plan

Emphasize:

1. Cruciferous vegetables, such as broccoli, cauliflower, cabbage, contain DIM and I3C.
2. Whole foods (foods that are as close to their natural form as possible)
3. Low sugar/low glycemic diet (Glycemic index (GI) and glycemic load (GL) are measures of the effect on blood glucose level after a food containing carbohydrates is consumed)
4. Omega-3 fatty acids, found in cold water fish such as sardines, wild-caught salmon, cod, mackerel, tuna
5. High fiber, from whole grains, beans, vegetables and fruits
6. Healthy fats, from avocados, nuts, seeds, olive oil, coconut oil, cold water fish
7. For animal protein, choose lean poultry and fish over red meat, and aim to view meat as a condiment rather than a staple. Try to choose grass fed and organic meats and eggs whenever possible. Eat no fish larger than a salmon to minimize environmental contaminants, including mercury.

Avoid:

1. Foods that have been treated with pesticides and herbicides, especially glyphosate
2. Processed and grilled meats. Also, try to limit intake of red meat
3. Fast foods, fried foods, baked goods and packaged, processed foods
4. Sugar, sweeteners and artificial sweeteners
5. Vegetable oils, shortening, margarine and anything with hydrogenated or partially hydrogenated oils

◄Lymphoma Supplement Protocol

CO Q 10 - Ubiquinol

• This antioxidant has been stated to improve survival rates in various forms of cancer as well as having cardioprotective influence on children with lymphoma.^[31] Cell studies show that coenzyme Q 10 reduced cell activity of malignant cells in Burkitt’s lymphoma.^[32]
• Suggested dose: 100 mg per day.

Curcumin Phytosome

• The active extract from the spice turmeric, curcumin has high anti-cancer effects on many cell lines, including lymphoma. Curcumin inhibited the growth of HL cell lines and increased the sensitivity to the chemotherapy cisplatin.^[21] Lymphoma tumor growth in mice was inhibited by curcumin.^[22],[23]
• Suggested dose: 1-2g per day of Meriva® or Longvida® curcumin.^[24],[25]

Indole-3-carbinol (IC3)

• IC3 was found to increase cell death in adult T-cell leukemia/lymphoma (ATLL) cells in both human and cell studies.^[18] Pregnant animals fed IC3 resulted in lower incidences of lymphoma in their offspring.^[19]
• Suggested dose: 200-400mg per day.

Pterostilbene & Resveratrol

• This antioxidant found in red wine and grapes inhibited Epstein Barr Virus (EBV) in Burkitt’s lymphoma cells.^[29] Additionally it induced cell death in Hodgkin lymphoma.^[30]
• Suggested dose: 100-200mg per day.

◄Additional Beneficial Supplements

Vitamin D

• Human trials have shown that low levels of vitamin D are related to a higher risk of developing T-cell lymphoma.^[15] Epidemiological findings demonstrate that time of year of diagnosis of Hodgkin’s lymphoma affects survival rates, with 20% lower rates of fatality if diagnosed in autumn rather than winter. The survival rate was 60% better for those under 30 years old. This may reflect the positive influence vitamin D levels have on the immune system and cancer fatality.^[16] In addition to monitoring 25(OH) levels, 1,25 dihydroxy-vitamin D levels also must be measured, as individuals with lymphoma may have a rapid conversion to this active form, and are at risk for vitamin D toxicity, even with modest doses of vitamin D.
• Suggested dose is that sufficient to raise vitamin D blood levels to >40 ng/mL, which may require 5000 IU per day or more.^[17] * Vitamin D must be used very cautiously at first in people who have lymphoma active in their body.

Diindolylmethane (DIM)

• DIM significantly reduced human T-cell acute lymphoblastic leukemia (T-ALL) cells as well as reducing lymphoma tumors in mice by as much as 44%.^[20]
• Suggested dose: 250 mg per day.

Quercetin

• Quercetin is a flavonoid which has shown to induce cell death in lymphoma cell lines.^[26] One cell study showed that quercetin combined with the drug rituximab enhanced the effectiveness of this drug in inhibiting diffuse large B-cell lymphoma (DLBCL) cells.^[27] TRAIL is an important cytokine needed for cell death that is often decreased in lymphoma cell lines. Quercetin restores TRAIL-induced cell death in resistant transformed follicular lymphoma B-cell lines.^[28]
• Suggested dose: 200-400mg, three times per day.

◄Footnotes

[1]Jaglowski SM1, Linden E, et al. Lymphoma in adolescents and young adults. Semin Oncol. 2009 Oct;36(5):381-418. doi: 10.1053/j.seminoncol.2009.07.009.

[2] Talamini R, Polesel J, Montella M, Maso LD, Crispo A, Spina M, Franceschi S, Crovatto M, La Vecchia C. Smoking and non-Hodgkin lymphoma: case-control study in Italy. Int J Cancer. 2005 Jul 1;115(4):606-10.

[3] Wu XC, Andrews P, Chen VW, Groves FD. Incidence of extranodal non-Hodgkin lymphomas among whites, blacks, and Asians/Pacific Islanders in the United States: anatomic site and histology differences. Cancer Epidemiol. 2009 Nov;33(5):337-46.

[4] Robbins HA, Shiels MS, Pfeiffer RM, Engels EA. Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States. AIDS. 2014 Mar 27;28(6):881-90.

[5] Leo QJ, Ollberding NJ, Wilkens LR, Kolonel LN, Henderson BE, Le Marchand L, Maskarinec G. Obesity and non-Hodgkin lymphoma survival in an ethnically diverse population: the Multiethnic Cohort study. Cancer Causes Control. 2014 Jul 29.

[6] Salem EA, Hegazy MM, El Khouley EA. Pesticide exposure as a risk factor for lymphoproliferative disorders in adults. East Mediterr Health J. 2014 Jun 18;20(6):363-71.

[7] Pahwa M, Beane Freeman L, Spinelli JJ, Blair A, Pahwa P, Dosman JA, McLaughlin JR, Demers PA, Hoar Zahm S, Cantor KP, Weisenburger DD, Harris SA. 0409 The North American Pooled Project (NAPP): Pooled analyses of case-control studies of pesticides and agricultural exposures, lymphohematopoietic cancers and sarcoma. Occup Environ Med. 2014 Jun;71 Suppl 1:A116.

[8] Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int J Environ Res Public Health. 2014 Apr 23;11(4):4449-527.

[9] Eriksson M, Hardell L, Carlberg M, Akerman M. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis. Int J Cancer. 2008 Oct 1;123(7):1657-63.

[10] Buckley JD1, Meadows AT, Kadin ME, et al. Pesticide exposures in children with non-Hodgkin lymphoma. Cancer. 2000 Dec 1;89(11):2315-21.

[11] Kokouva M1, Koureas M, Dardiotis E, et al. Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population. Toxicology. 2013 May 10;307:12-6. doi: 10.1016/j.tox.2012.07.003. Epub 2012 Jul 16.

[12] Fallah M1, Liu X2, Ji J2, Försti A3, et al. Autoimmune diseases associated with non-Hodgkin lymphoma: A nationwide cohort study. Ann Oncol. 2014 Jul 31. pii: mdu365. [Epub ahead of print]

[13] Cohen L1, Warneke C, Fouladi RT, et al. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer. 2004 May 15;100(10):2253-60.

[14] Teras LR, Gapstur SM, Diver WR, Birmann BM, Patel AV. Recreational physical activity, leisure sitting time and risk of non-Hodgkin lymphoid neoplasms in the American Cancer Society Cancer Prevention Study II Cohort. Int J Cancer. 2012 Oct 15;131(8):1912-20. doi: 10.1002/ijc.27445. Epub 2012 Mar 8.

[15] Drake MT, Maurer MJ, Link BK, Habermann TM, Ansell SM, Micallef IN, Kelly JL, Macon WR, Nowakowski GS, Inwards DJ, Johnston PB, Singh RJ, Allmer C, Slager SL, Weiner GJ, Witzig TE, Cerhan JR. Vitamin D insufficiency and prognosis in non-Hodgkin’s lymphoma. J Clin Oncol. 2010 Sep 20;28(27):4191-8.

[16] Porojnicu AC, Robsahm TE, Ree AH, Moan J. Season of diagnosis is a prognostic factor in Hodgkin’s lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005 Sep 5;93(5):571-4.

[17] Garland CF, French CB, Baggerly LL, et al. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res. 2011 Feb;31(2):607-11.

[18] Machijima Y, Ishikawa C, Sawada S, Okudaira T, Uchihara JN, Tanaka Y, Taira N, Mori N. Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol. Retrovirology. 2009 Jan 16;6:7. doi: 10.1186/1742-4690-6-7.

[19] Yu Z, Mahadevan B, Löhr CV, Fischer KA, Louderback MA, Krueger SK, Pereira CB, Albershardt DJ, Baird WM, Bailey GS, Williams DE. Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo

[a,l]pyrene. Carcinogenesis. 2006 Oct;27(10):2116-23. Epub 2006 May 16.

[20] Shorey LE, Hagman AM, Williams DE, Ho E, Dashwood RH, Benninghoff AD. 3,3′-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells. PLoS One. 2012;7(4):e34975. doi: 10.1371/journal.pone.0034975. Epub 2012 Apr 13.

[21] Kewitz S, Volkmer I, Staege MS. Curcuma Contra Cancer? Curcumin and Hodgkin’s Lymphoma. Cancer Growth Metastasis. 2013 Aug 8;6:35-52. doi: 10.4137/CGM.S11113. eCollection 2013.

[22] Das L, Vinayak M. Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice. Int Immunopharmacol. 2014 May;20(1):141-7.

[23] Zhu G, Zhang Q, Dai H, Shen Q.

[Effect of curcumin on expressions of mitogen-activated protein kinases and matrix metalloproteinases in Jurkat cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2013 Dec;33(12):1792-5.

[24] Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol. 2007 Jul;60(2):171-7.

[25] DiSilvestro RA1, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79. doi: 10.1186/1475-2891-11-79.

[26] Peng X, Yu DY, Feng BM, Wang YQ, Shi LY. A new acylated flavonoid glycoside from the flowers of Camellia nitidissima and its effect on the induction of apoptosis in human lymphoma U937 cells. J Asian Nat Prod Res. 2012;14(8):799-804.

[27] Li X, Wang X, Zhang M, Li A, Sun Z, Yu Q. Quercetin Potentiates the Antitumor Activity of Rituximab in Diffuse Large B-Cell Lymphoma by Inhibiting STAT3 Pathway. Cell Biochem Biophys. 2014 Jun 6.

[28] Jacquemin G, Granci V, Gallouet AS, Lalaoui N, Morlé A, Iessi E, Morizot A, Garrido C, Guillaudeux T, Micheau O. Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin’s lymphoma B cells. Haematologica. 2012 Jan;97(1):38-46. doi: 10.3324/haematol.2011.046466. Epub 2011 Sep 20.

[29] De Leo A, Arena G, Lacanna E, Oliviero G, Colavita F, Mattia E. Resveratrol inhibits Epstein Barr Virus lytic cycle in Burkitt’s lymphoma cells by affecting multiple molecular targets. Antiviral Res. 2012 Nov;96(2):196-202.

[30] Frazzi R, Valli R, Tamagnini I, Casali B, Latruffe N, Merli F. Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation. Int J Cancer. 2013 Mar 1;132(5):1013-21.

[31] Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review. Health Technol Assess. 2007 Jul;11(27):iii, ix-x, 1-84.

[32] Bruge F, Virgili S, Cacciamani T, Principi F, Tiano L, Littarru GP. NAD(P)H:quinone oxidoreductase (NQO1) loss of function in Burkitt’s lymphoma cell lines. Biofactors. 2008;32(1-4):71-81.