Rama Bhagwat
Research paper written July 2019, summer after my freshman year of high school
Abstract
Non-Hodgkin’s Lymphoma is one of the most common types of Lymphomas, especially within the middle aged population. Unlike Hodkin’s Lymphoma, Non-Hodgkin’s Lymphoma is marked by an absence of Reed-Sternberg cells. Currently, scientists have found 4 main treatment methods to help cure this type of cancer. These include Chemotherapy, Radiation Therapy, Targeted Therapy, and Immunotherapy. Each of these treatment methods are still being improved upon, going through numerous clinical trial to increase maximum efficiency. While all of these options have been proven to work in the long run, there are numerous downfalls that come with each. Some treatments, such as chemotherapy and radiation therapy, don’t discriminate upon which cells they kill. While they are very efficient at destroying cancerous matter, they also kill healthy cells that a human would need for basic functions. On the other hand, immunotherapies and targeted therapies almost completely ignore the tumors themselves, instead focusing on strengthening the immune system.
What Is Non-Hodgkin’s Lymphoma?
Non-Hodgkin’s Lymphoma is a type of blood cancer that accounts for 4% of all cancers. Within blood cancer, it falls within the sector of Lymphomas. Lymphoma is a type of cancer that occurs within the lymphocytes, which are infection fighting cells that help make up the immune system. These cells can be found all over the body, most notably the lymph nodes, bone marrow, spleen, and thymus. There are two notable types of lymphoma: Non-hodgkin’s lymphoma and Hodgkin’s lymphoma. While they share a name and are similar in concept, they have core differences [Figure 1]. The main similarity between these two types is that in Hodgkin’s Lymphoma, there is a presence of Reed-Sternberg cells. In Hodgkin’s Lymphoma, these types of cells represent foreign matter. These cause issues in helper B cells, which are an important part of the immune system. On the other hand, Non-Hodgkin’s Lymphoma does not have these cells(9).
Prognosis of Non-Hodgkin’s Lymphoma
Unlike Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma is often diagnosed at later stages, making it more difficult to treat. Usually those who contract the disease prior to the age of 60 have a more promising prognosis of this disease than those over 60. Likewise, despite age, those at earlier stages have a higher survival rate than those whose disease has progressed to a later stage.
There are four main stages of Non-Hodgkin’s Lymphoma, with stage 1 being the least severe and the fatality rate going up with each stage. At stage 1, usually only one of the lymph nodes is affected by cancer. This makes it very easy to remove and treat. Upon entering stage 2 more than one of the lymph nodes – either in multiple locations or a cluster – are affected by the cancerous cells. However, due to their relative location, these are also easier to treat. One similarity between stage 1 and 2 is that the disease stays above the diaphragm. In stage 3, the cancer spreads to lymph nodes both above and below the diaphragm, making it harder to target. In the final stage of Non-Hodgkin’s Lymphoma, the cancer has finally spread into the bloodstream and the body, transferring to other organs (1). At this point in time, the cancer is almost incurable as it is in so many parts of the body.
Usually, those at risk for Non-Hodgkin’s Lymphoma are at a median age of 59. People are more likely to acquire this type of cancer if they have a weak immune system, as the cancer targets immune cells. Immunosuppressant drugs can be a risk factor, along with any diseases that lower immune response, such as HIV. There are a variety of tests that need to be done in order to diagnose Non-Hodgkin’s Lymphoma. These include X-Rays, CT scans, MRIs, and PET scans. Physical exams can show swollen lymph nodes, and an enlarged liver or spleen. Some common symptoms of Non-Hodgkin’s Lymphoma include: abdominal pain and swelling, pain, respiratory problems, fever and other flu symptoms, and swollen lymph nodes.
How Is It Treated?
Currently, there are 4 major ways to treat and potentially cure Non-Hodgkin’s Lymphoma. Some of these methods have been around for a year, and are just minorly changed to target the specific cancer as a whole. These include chemotherapy and radiation. While useful for killing the specific cancers as a whole, there is very little differentiation between the different patient’s experiences. Now, however, there are two new methods that are being more and more commonly used to treat cancers such as Non-Hodgkin’s Lymphoma. These include a variety of different immunotherapies, and new targeted therapy drugs/vaccines.
Chemotherapy
Chemotherapy is the most commonly used method of treating cancer. chemotherapy is the use of a variety of drugs that are injected into the body in order to kill cancerous cells. Cancer spreads by rapidly multiplying, spreading throughout the body and taking over the natural resources, crowding healthy cells out. Even one cancerous Non-Hodgkin’s Lymphoma cell can soon spread to two, then four, eight, sixteen, and so on. Within a matter of days the condition can get severely worse. Therefore, it is very important to kill off all the cancerous cells. chemotherapy utilizes a cocktail of different cell-killing chemicals, and the mixture varies based on the type of cancer. There are 6 groupings of the chemicals used: Alkylating agents, Corticosteroids, Platinum drugs, Purine analogs, Anti-metabolites, and Anthracyclines(3). Each of these families have 3-4 chemicals within them, and each have their own purpose. When curing Non-Hodgkin’s Lymphoma, the most common combination is known as CHOP (2) (3). CHOP consists of 4 different drugs: Cyclophosphamide, Doxorubicin, Prednisone, and Vincristine (2). One of the benefits of chemotherapy is that it can be combined with other treatments, such as radiation. Those still in stages 1 or 2 usually will receive anywhere from 3 to 6 cycles of chemotherapy along with radiation. Those in the latter stages often might experience 6 or more cycles of the treatment, along with a variety of tests and other treatments (12). chemotherapy has been proven to work in certain forms of cancer, as it very effectively kills off all cells it comes in contact with. However, chemotherapy does not discriminate from the patient’s healthy cells and the dangerous cancer cells. Therefore, while killing the cancer, it is also killing the host’s body. Many chemotherapy patients experience basic symptoms such as nausea, hair loss, smaller appetites, and fatigue. However, there are also some serious long term effects, such as fertility issues and susceptibility to illnesses. While chemotherapy is one of the most common treatments for cancer, it is not fully sustainable on it’s own and doesn’t cater to the victim’s specific cancer.
Radiation Therapy
Radiation Therapy is another method that is often used to treat a multitude of different cancers, including Non-Hodgkin’s Lymphoma. Often used alongside other treatments such as chemo, radiation therapy utilizes high energy x-rays, along with different types of radiation waves to go through the body and kill cancerous cells. Usually, this therapy is used following chemotherapy treatment, as it ensures any remaining cancer cells are destroyed. It can also be used to treat small localized cancerous cells, as it only affects a small portion and not the entire body (2) (13). Cancer cells have a specific type of DNA that, when healthy, allows it to keep multiplying [Figure 2]. This form of cancer therapy works by sending a variety of UV radiation cells into a specific part of the body. The UV radiation damages and breaks the cells’ DNA, rendering it useless [Figure 3] (13). This helps fight cancer as the cancerous tumor’s DNA is damaged, and they are unable to multiply and spread.
While radiation can be an effective way to help cure and get rid of cancerous cells, there are a multitude of side effects. For example, excess radiation exposure can actually cause more cancerous cells to occur. While it destroys the DNA from cancerous cells, it also destroys the DNA from healthy cells, leaving them susceptible to various mutations. It can also cause similar side effects to chemo.
Targeted Therapies
Targeted therapies are types of treatments and drugs that focus specifically on the genetic makeup of the patient and the type of cancer that they are experiencing. Scientists have discovered that not all tumors target the same genes, and this revelation has allowed doctors and researchers to begin working on drugs to target the specific tumor suppressor genes, among other things (2). Many recent breakthroughs have been made targeting specific parts of the Non-Hodgkin’s Lymphoma cells, such as those regulating cell signals and apoptosis (5). Other options include drugs that help radioactive material bind to the Non-Hodgkin’s Lymphoma tumors, successfully killing only the foreign cells. One of the newest ideas included a vaccine for Non-Hodgkin’s Lymphoma. Vaccines are traditionally only used for viruses. A dead virus is injected into the bloodstream, allowing for the white blood cells to memorize it and recognize it later on. These types of cancer viruses use the same ideas. Cancer neoantigen vaccines help the immune system recognize the foreign tumor cells, and helps trigger a T-cell response. In two stage 1 clinical trials, it has been proven that these vaccines do in fact help the immune system recognize traces of cancerous cells ahead of time, and trains them to kill it (7). Recently scientists have also been attempting to combine this vaccine with a checkpoint inhibitor. A second clinical trial is underway to test the effectiveness of this. The theory is that, in combination with the vaccine, would not only stop the cells from multiplying but also killing the existing cells. These vaccines are developed using human cells ex-vivo, and there have been multiple types of cancers (7) (Figure 4).
Unlike the previous methods mentioned, targeted therapies are more customized to the genetics. Side effects have not been fully documented due to the ongoing clinical trials, but since they target only specific cells they eliminate the possibility of killing healthy cells. This also allows the immune system to continue and try to fight the cancer itself, and help it recognize it for later on.
Immunotherapies
Immunotherapy is the newest and most popular type of cancer treatment among modern day scientists. As opposed to targeting the specific cancer cells like the previous treatments mentioned, immunotherapy drugs and techniques instead focus on boosting the immune system. Similar to targeted therapies, such as the vaccine, immunotherapies are very specific to the specialized cell DNA (2). One of the types of immunotherapy treatments that are undergoing research is the use of CAR-T cells. In this form of treatment, the T cells of an individual are taken out of a person’s blood and taken to a laboratory (Figure 5). Here, scientists reengineer the cells and add new DNA to the cell, producing CAR antibodies on the surface of the cell, hence giving them the name CAR-T cells. These cells then are grown in large numbers within a laboratory and frozen to preserve them. Once a sufficient amount has been collected, these cells are thawed and placed back into the patient’s bloodstream (15). With the newfound antibodies, the body and immune system of the victim are able to better recognize tumor cells, even those that are hidden and unmarked. There are multiple forms of this that are already FDA approved and ready to be used in the market (15) (16). However, very few commercial hospitals actually offer these treatments. The two currently approved by the FDA are Axicabtagene Ciloleucel and Tisagenlecleucel. Axicabtagene is specifically for adults with Non-Hodgkin’s Lymphoma and large B cell lymphoma, while Tisagenlecleucel are more used for those in remission to keep the disease from being reintroduced (16). Overall, immunotherapies are the most promising type of treatment, as it not only cures cancer without harming working cells, but as it also allows for the immune system to grow and recognize cancer, preventing its reintroduction.
Conclusion
Making up 4% of all cancers in the US population alone, Non-Hodgkin’s Lymphoma is one of the most common types of lymphomas. Characterized by a lack of Reed-Sternberg cells, and specifically targeting lymphocytes, scientists have found 4 main treatment methods: chemotherapy, radiation therapy, targeted therapy, and immunotherapy. While many are still undergoing clinical trials, they have been proven to be efficient in the long run. Despite the obvious benefits, there are multiple downfalls that come with each method. Chemotherapy and radiation therapy, while very efficient at destroying the foreign cancerous cells, also target healthy cells that are sometimes vital for survival. Immunotherapies and targeted therapies instead focus on strengthening and teaching the immune system how to detect the hidden cells, but scientists have yet to find a safe, cheap, and efficient way to mass distribute these techniques to the general public. With personalized healthcare becoming more common, these methods are becoming more and more intriguing, and could one day provide the ultimate cure for cancer.
SOURCES:
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