Non-Hodgkin Lymphoma

Rachna Sehgal, Dr. Lopamudra Das Roy

Published 2021

Abstract

This paper explores the implications of Non-Hodgkin Lymphoma, a cancer that originates in the body’s lymphocytes, a special type of white blood cell that specializes in the body’s immunity. This paper discusses the incidence of this cancer among global populations as well as its occurrence, common symptoms, prevention techniques, and treatments. This paper utilized a wide array of sources, including websites of several renowned cancer organizations (cancer.org, mayoclinic.org, and clevelandclinic.org) as well as databases such as the National Institute of Health and PubMed. All in all, this paper details how B-cell lymphoma is the most common type of Non-Hodgkin diagnosed nationwide. It further discusses how Non-Hodgkin ly lymphomas are more prevalent in developed countries, rather than developing countries. The purpose of this paper is to inform the general public of Non-Hodgkin Lymphoma in layman terms and to dispel any common incorrect information that is associated with this cancer.

About Non-Hodgkin Lymphoma (NHL)

Cancer is usually simply defined as a disease, in which cells of a specific organ, tissue, or type begin to grow out of control [1]. In NHL, cancer usually originates in the lymphocytes, a special type of white blood cell that specializes in the body’s immunity, which goes on to infect the body’s lymph system. The lymph system is a significant part of the body’s immune system and helps out by moving fluids through the body. Essentially, lymphomas can origin in any part of the body that is made of lymph tissue, including but not limited to the lymph nodes, bone marrow, spleen, thymus, digestive tract, and adenoids and tonsils. There are two main types of lymphoma: B-cell lymphomas and T-cell lymphomas [2]. B-Cell lymphomas account for over 85% of all NHL cases, while T-cell lymphomas account for less than 15% [3]. In order for doctors to correctly treat lymphoma, they must be able to accurately distinguish between them. In B-cell lymphomas, the cancer attacks b-cells that are involved in creating antibodies, which in turn help protect the body from bacteria and viruses by attaching onto and destroying them. In T-cell lymphomas, the cancer attacks the-cells that are involved in boosting or slowing down the components of the immune system [2]. Doctors further classify lymphomas based on how fast or slow spreading they are into two categories: indolent lymphomas and aggressive lymphomas [2]. Indolent lymphomas are slow-growing and slow-spreading, and instead of being treated, most healthcare professionals choose to closely monitor their progress: the most common type is follicular lymphoma [2]. Aggressive lymphomas, on the other hand, are fast-growing and rapid spreading. They need to be treated right away to prevent metastasis, which occurs when the cancer spreads away from its original area. Non-Hodgkin lymphomas can further be classified by how rapidly they grow. Low-grade NHL include Marginal Zone lymphoma, Mucosa-Associated lymphoid tissue lymphoma, Follicular lymphoma, and Mantle Cell lymphoma. Intermediate grade NHL are commonly known as Primary Mediastinal Large Cell lymphoma, Anaplastic Large Cell lymphoma. Finally, high-grade non-Hodgkin lymphoma includes Burkitt’s lymphoma and Lymphoblastic lymphoma [1]. Though some lymphomas do not necessarily fall under either of these categories, it is extremely important for doctors to classify them as such so that they take the next appropriate measures to treat their patient [2].

Symptoms/Screening [4]

Risk Factors and Causes

Risk factors increase your chance of getting cancer. There are several risk factors associated with developing NHL over a period of time, including having family history (especially having a parent or sibling develop NHL), being exposed to radiation in any time in life, and having autoimmune diseases, such as Sjogren disease, rheumatoid arthritis, systemic lupus erythematosus, and celiac disease [5]. Being overweight, smoking, and not following a healthy lifestyle that includes plenty of exercise and the consumption of water and fresh fruits and vegetables can also lead to many able-bodied adults to develop NHL [6]. Furthermore, having a weakened immune system due to HIV/AIDS, organ transplants, or injuries can further increase the risk for NHL. Certain infections can over time lead lymphocytes, including the Epstein-Barr virus [6], human herpesvirus 8, and t-cell lymphotropic virus, manifesting themselves into the disease [5].Finally, the most significant risk factor for lymphomas is age. NHL is more likely to occur in adults over the age of 60 as the lymph system weakens; however, as always, there are notable exceptions [7], and though doctors are not exactly sure why or how it manifests itself in children, they have narrowed it down to two significant risk factors: a weak immune system (especially after having an organ transplants or severe injuries) and congenital immune deficiency syndromes (specifically Wiskott-Aldrich syndrome or Severe combined immunodeficiency syndrome) [8]. Oftentime, no cause at all (include). Though there is no pinpoint cause to NHL [6], scientists accept a variety of hypotheses, pertaining to the changes of genes and significant differences in the body’s immune system [15]. Because cancers are usually caused by mutations that allow tissues to continuously reproduce cells, many scientists have concluded that people with NHL inherit genes that contain mutagens in lymphatic cells. Later on in life, these mutations are activated either randomly or by environmental factors (such as exposure to radiation/carcinogens, onset of autoimmune diseases) and disrupt the regular life cycle of lymphatic cells, leading to the development of NHL. Oftentimes, NHL can be attributed to no reason at all [15]. Significant transitions in the body’s immune system can create an unstable and weak environment, in which NHL can manifest itself in. People who undergo organ transplants, diagnosed with HIV/AIDs, or exposed to immune-system weakening drugs as well as individuals with autoimmune or chronic diseases are more likely to develop lymphomas due to further weakened immune systems [15].

Prevention/Early Detection in Developed & Developing Countries

Like most cancers, there is no tangible way to prevent NHL. The best course of action for the general population is to follow a healthy lifestyle: maintaining a healthy weight level, exercising moderately daily, and consuming a healthy diet, including plenty of fruits, vegetables, and non-sugary beverages [9]. Maintaining a healthy lifestyle is especially important as it keeps the body's immune system strong and less likely to be affected by mutagens. Populations can also practice safe sexual intercourse to limit the risk for sexually transmitted diseases that can weaken the immune system, primarily herpesvirus8 and HIV/AIDS. People can also attempt to limit their radiation exposure and avoid behaviors that put them at risk for developing Hepatitis C [9]. NHL also can't be prevented in children, so parents should ensure that their children practice a healthy lifestyle, don't come in contact with radiation, and are aware of the autoimmune diseases their child is diagnosed with are the best measures to decrease risk [8]. Raising awareness and preventing the spread of the T-cell lymphotropic virus (an infection that gradually develops into lymphoma) in city settings in the U.S. and the Caribbean can also keep rates of lymphomas low [10]. There is no singular early detection test for people who have no symptoms, so the best thing for the general population to do is to be aware and pay attention to any possible signs and symptoms [10]. There is no set early detection test or screening for NHL. The best way to catch it in its early stages is to be informed about its signs and symptoms so that patients can get individual screenings to test for it, so the best measure the general population can take is to be aware and pay attention to any possible signs and symptoms. Due to the lack of education and awareness, people in developing countries often do not get the care or recognize the symptoms of the disease until it is too late and are likely to detect it much later than those in developed countries. This is another reason why NHL is more associated with developed countries, rather than developing countries.

Treatment

When diagnosed with NHL, there are a variety of options for treating a patient. Patients can choose a combination of treatments or a single treatment depending on how late the lymphoma is detected. If the lymphoma is indolent (or slow-growing and contained in one area of the lymph system), the healthcare provider may suggest active surveillance before taking the next step. The most common course of treatment for NHL is chemotherapy, which uses a combination of drugs to target and kill cancer cells. Patients ingest these drugs, or they are injected into the patient's veins. Chemotherapy is also the best course of treatment when treating a lymphoma that came back after initial treatments [11]. Chemotherapy is also the best option for treatment when a patient has to undergo a bone marrow transplant, as it helps prepare the body for the transplant [11]. Another well-known treatment for NHL is radiation therapy. Radiation therapy utilizes high-powered energy beams, such as protons and X-rays, from a high-powered machine, which moves around the patient while directing beams at affected areas. Healthcare providers use radiation therapy when the lymphoma is contained in one part of the body, or when the lymphoma is slow-growing. Radiation therapy is also used to kill off any remaining cancer cells after chemotherapy [11].Targeted drug therapy is another viable option. In this treatment, monoclonal antibodies bind to affected lymphocytes and block growth pathways for lymphoma cells; it is important to note that the antibodies do not affect normal cells [12]. CAR-T (Chimeric Antigen Receptor) cell therapy is another viable option for patients who haven't done well with other treatments. In this treatment, special engineered cells utilize the body's T-cells (another type of lymphocyte) to fight cancer cells [11]. Immunology, a relatively new therapy, is also a viable option to treat patients. Immunology utilizes the body's natural defense mechanisms to identify and fight off cancer-affected cells [12]. Bone marrow transplants are usually the last option. These transplants altogether rid the body of affected lymphocytes and work to strengthen the immune system. If all other options fail, depending on the case, a patient may be eligible to participate in a clinical trial, which utilizes and tests new cancer therapies [12].

Statistics

Non-Hodgkin lymphoma is a relatively common cancer and is the seventh most diagnosed cancer in women in the U.S. American governmental cancer society predicts around 77,000 new diagnoses of NHL annually. However, as technology advances in developed countries, survival rates are at an all time high. An early diagnosis case has around an 83% survival rate in the U.S., and NHL, even in its most advanced stages, has a survival rate that averages more than 60% [13].In 2021, 20,720 people (of both sexes and all ages) in the U.S. are predicted to die from NHL [14]. Likewise, in 2021, 630 people (of both sexes and all ages) in North Carolina are expected to die from NHL [14]. Furthermore, in the U.S, the chance of a woman developing NHL in their lifetime is 1 in 52, while the chance of a man developing NHL in their lifetime is 1 in 41 [14]. As our population of elderly people increases in the coming years, epidemiologists believe that the incidence of NHL will increase.

As the table displays, while there is plenty of information available concerning the rates of new cases of NHL nationally and regionally, there is virtually no information that conveys the incidence of NHL in developing countries. This again shows how it is crucial to track and verify cases of NHL internationally, so that epidemiologists and researchers can learn more about the cancer and where it occurs.

Global Scenarios

Ethnicity/Gender Incidence

In the U.S., White Americans are more likely to get NHL than African American, Asian, Hispanic, and Middle Eastern populations. All in all, NHL is more prevalent in developed countries, such as those in Europe, the U.S., and Canada having the highest rates of diagnoses [1]. This is partly due to the fact that NHL is more likely to occur in older people, and these countries have higher life expectancies than developing countries, leading developed countries to have more at-risk and diagnosed populations. In developed countries, males are more likely to be diagnosed than females for NHL [15]. There is not too much available on NHL and it is being diagnosed in developing countries, due to a critical lack of accurate data [15]. In the coming years, it would be wise to collect it so that epidemiologists and researchers can learn more about cancer and where it occurs.

Socioeconomic Factors

Socioeconomic factors do come into play when determining which populations are affected the most by NHL. People from low-income areas and developing countries are more likely to not lead a healthy lifestyle due to not consuming clean water and a healthy diet. These groups of people are likely exposed to cancer-causing chemicals throughout their entire life due to poor living and working conditions. People in developing countries in Africa are also commonly exposed to viruses such as H. pylori and immune-weakening STDS. Due to the poverty and lack of education that exists in developing countries, most populations in these areas do not have the means to be treated or even diagnosed with such illnesses. As these illnesses progress, they weaken the body's central immune system, further increasing the risk for NHL. Finally, in developing countries, particularly in the African subcontinent, having genes or being diagnosed with Epstein-Barr virus (EBV) increases the risk of children and adults developing Burkitt lymphoma [16]. The associated risk runs as high as 50% [16]. Again, due to the impoverished state of developing countries, spreading awareness and educating populations is the only way early detection can occur [16]. In conclusion, these factors in developing countries and low-income areas are likely to increase the risk for developing NHL.

Conclusion

In conclusion, Non-Hodgkin lymphoma is the 7th most common cancer in the U.S. It is a highly complex disease, and there are many aspects of it that scientists are still trying to figure out. There are two main types of lymphomas: B-Cell lymphomas and T-cell lymphomas. B-cell lymphomas make up about 75% of the diagnosed cases in the U.S., while T-cell lymphomas account for only about 15% of the cases. There are a wide array of risk factors that make people susceptible to developing NHL, including exposure to radiation, previous diagnosis of autoimmune or sexually transmitted diseases, and family history. People who do not lead a healthy lifestyle are also likely to develop NHL. NHL does not affect people in the U.S. equally. In fact, NHL is most likely to affect white populations older than the age of 60, than any other ethnicity in the U.S. Due to the lack of resources for education and awareness available in developing countries, people in these areas are likely to miss out on the symptoms of the cancer and not get diagnosed in time. In fact, data for NHL rates in developing countries is not the most accurate, and in the coming years, it would be wise to start tracking the illnesses so that epidemiologists and health professionals can learn more about the prevalence of the disease.

References

1. Non-Hodgkin Lymphoma: Overview." A Non-Profit Hospital in Los Angeles | Cedars-Sinai, 21 Feb. 2021, www.cedars-sinai.org/health-library/diseases-and-conditions/n/non-hodgkin-lymphoma-overview.html. Accessed 9 Aug. 2021.

2. "What Is Non-Hodgkin Lymphoma?" American Cancer Society | Information and Resources About for Cancer: Breast, Colon, Lung, Prostate, Skin, 12 Jan. 2021, www.cancer.org/cancer/non-hodgkin-lymphoma/about/what-is-non-hodgkin-lymphoma.html. Accessed 9 Aug. 2021.

3. "Non-Hodgkin Lymphoma." MD Anderson Cancer Center, www.mdanderson.org/cancer-types/non-hodgkin-lymphoma.html. Accessed 9 Aug. 2021.

4. Roy, Lopamudra Das. “Non-Hodgkin Lymphoma Early Detection Card.” Breast Cancer Hub, Breast Cancer Hub, 9 June 2021.

5. "Non-Hodgkin Lymphoma Risk Factors." American Cancer Society | Information and Resources About for Cancer: Breast, Colon, Lung, Prostate, Skin, 9 June 2020, www.cancer.org/cancer/non-hodgkin-lymphoma/causes-risks-prevention/risk-factors.html.

6."Non-Hodgkin (Non-Hodgkin's) Lymphoma." Johns Hopkins All Children's Hospital, www.hopkinsallchildrens.org/Patients-Families/Health-Library/HealthDocNew/Non-Hodgkin-Lymphoma. Accessed 9 Aug. 2021.

7. "Non-Hodgkin and Non-Hodgkin Lymphoma Risk Factors." Rogel Cancer Center | University of Michigan, 27 Dec. 2019, www.rogelcancercenter.org/blood-cancer/resources-patients/leukemia-and-lymphoma-awareness/lymphoma-risk-factors. Accessed 9 Aug. 2021.

8. "Risk Factors, Causes, and Prevention of Non-Hodgkin Lymphoma in Children." ACCO, 15 Aug. 2019, www.acco.org/blog/risk-factors-causes-and-prevention-of-non-hodgkin-lymphoma-in-children/. Accessed 9 Aug. 2021.

9. "Non-Hodgkin’s Lymphoma." Cleveland Clinic, 15 Sept. 019, my.clevelandclinic.org/health/diseases/15662-adult-non-hodgkins-lymphoma. Accessed 9 Aug. 2021.

10. "Can Non-Hodgkin Lymphoma Be Prevented?" American Cancer Society | Information and Resources About for Cancer: Breast, Colon, Lung, Prostate, Skin, 9 June 2020, www.cancer.org/cancer/non-hodgkin-lymphoma/causes-risks-prevention/prevention.htm

11."Non-Hodgkin's Lymphoma - Diagnosis and Treatment - Mayo Clinic." Mayo Clinic - Mayo Clinic, 10 Apr. 2018, www.mayoclinic.org/diseases-conditions/non-hodgkins-lymphoma/diagnosis-treatment/drc-20375685. Accessed 9 Aug. 2021.

12. "Non-Hodgkin Lymphoma." MD Anderson Cancer Center, www.mdanderson.org/cancer-types/non-hodgkin-lymphoma.html. Accessed 9 Aug. 2021.

13. "Cancer Facts & Statistics." American Cancer Society | Cancer Facts & Statistics, 2020, cancerstatisticscenter.cancer.org/#!/cancer-site/Non-Hodgkin%20lymphoma.

14. "Key Statistics for Non-Hodgkin Lymphoma." American Cancer Society | Information and Resources About for Cancer: Breast, Colon, Lung, Prostate, Skin, 21 Jan. 2021, www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html#written_by. Accessed 2 Aug. 2021.

15. Becnel, Melody et al. “Disparities in lymphoma on the basis of race, gender, HIV status, and sexual orientation.” Annals of lymphoma vol. 1 (2017): 8. doi:10.21037/aol.2017.11.01

16. Shannon-Lowe, Claire et al. “Epstein-Barr virus-associated lymphomas.” Philosophical transactions of the Royal Society of London. Series B, Biological sciences vol. 372,1732 (2017): 20160271. doi:10.1098/rstb.2016.0271

Lopamudra Das RoyOctober 20, 2021