Jordan's+Journey

“Eagles on three! One…two…three…EAGLES!” Jordan chanted as his high school football team completed practice for the day in early spring. “Great passing today, Jordan. Make sure you ice that arm if you’re sore,” Coach Nelson remarked as Jordan strode off the field, massaging his underarm. “Thanks, coach,” Jordan replied. Considering he had just been throwing footballs for the past two hours, the eighteen year old did not think much of the mild irritation and small lump he felt under his arm. He returned home to his mother, father, and younger sister, ate dinner with the family, iced his underarm, and went to sleep.

Jordan woke up at three in the morning in a cool sweat. He felt as though he had climbed out of a swimming pool in his boxers and undershirt before diving into bed the night before. His blond hair, matted with sweat, appeared almost black. “God damn D.C summers,” he cursed under his breath as he descended the stairs into his family’s kitchen for a glass of water. Jordan had misattributed his second symptom to the notoriously humid August weather in the mid-Atlantic. He changed his sleepwear and returned to bed.

By mid-October, autumn and the football season were in full swing. Jordan had begun feeling fatigued and had a lingering cough. He often came down with seasonal colds, but his dry cough accompanied by occasional chest pains were not at all the run of the mill cold symptoms he was used to, so he decided to schedule an appointment with his family doctor.

“Mr. Brewer,” the nurse called as Jordan sat in the waiting room at his doctor’s office. He stood up, coughed a bit, and followed the nurse back to an examination room. The nurse took his vital signs and checked his height and weight, as was routine. “Well Jordan, it looks like you’ve lost some weight since you’ve last been here. Has your diet or exercise regimen changed?” the nurse inquired. “No, nothing has changed,” Jordan replied. “What exactly brought you in today?” asked the nurse. “Well, I’ve been coughing for about three weeks, and I have chest pains sometimes,” responded Jordan. The nurse listened to his chest and could hear wheezing near the top of his lung caused by a tumorous lymph node in his chest pressing against his windpipe. She jotted down a few notes, “The doctor will be right in.”

“Hello, Jordan,” Dr. Nagy spoke as he entered the examination room. “I see you have a cough and some chest pain,” the doctor spoke as his eyes scanned over the notes the nurse had left. “Yeah, I’ve had a dry cough for like three weeks,” Jordan replied. The doctor pressed his stethoscope to Jordan’s chest, and Jordan took a deep breath. “It sounds like you have some wheezing in your chest. Have you had any other symptoms lately?” Jordan massaged his underarm while he thought. “Nothing related to the cough, but I have a small lump under my arm.” “How long ago did you notice this?” the doctor asked as he felt the lump. Jordan thought back, “I noticed it last spring at football practice.” Arms crossed, the doctor clenched his jaw and stared at the floor for a moment. He looked up and made eye contact with Jordan, “I think you should have this lump biopsied.” The following week, Jordan had an outpatient procedure performed to remove a piece of the tumorous lymph node under his arm. The excavated piece of tissue was examined by a pathologist who determined that cancerous lymphocytes—also known as Reed Sternberg cells —were present in the lymphoid tissue. Jordan was diagnosed with Nodular Sclerosis Hodgkin’s disease: a cancer of the lymphatic system most common in teens and young adults.

Jordan was numb, he sat motionlessly on the grey examination table against the wall in the unfamiliar office of his new oncologist. “Hi, I’m Dr. Andersen” “Hi,” Jordan emotionlessly responded. For the rest of the appointment, Dr. Andersen explained to Jordan that he has stage two Nodular Sclerosis Hodgkin’s disease. The oncologist hypothesized that the cancer started in the lymph node under Jordan’s throwing arm and pressed on nearby nerves, causing the soreness. He explained that though the link between the two is unclear, the fact that Jordan had previously had mononucleosis—an Epstein-Barr viral infection —was a risk factor for developing Hodgkin’s disease, which most likely arose from a random DNA mutation in a B lymphocyte in his underarm. He also explained that because his younger sister had not had the disease, Jordan had no major risk factors for developing the cancer outside of being a white, teenage male—the most likely demographic to develop this form of Hodgkin’s disease[|[4]]. Dr. Andersen went on to explain that the cancer most likely spread across the lymph system to a lymph node in Jordan’s chest. This lymph node in his chest then became tumorous and began to press on his right bronchial tube, causing his cough and chest pain. The oncologist staged Jordan’s cancer as stage two, because it was present in two lymph nodes in his upper torso Had the cancer been detected before it spread to the lymph node in Jordan’s chest, it would have been considered stage one; had the cancer spread below Jordan’s diaphragm, it would have been stage three, and had the cancer spread to multiple, distant lymph nodes as well as nearby organs, it would have been stage four . The doctor explained that the cancer only being stage two was relatively good news as the five year survival rate of patients with stage two Hodgkin’s lymphoma is ninety percent.

 Jordan’s oncologist met with him and his parents to discuss what kind of treatment Jordan should undergo in order to rid his body of the cancerous cells traveling through his lymphatic system. Dr. Andersen spoke about how he usually suggests starting with a chemotherapy regimen due to the possible long lasting side effects of radiation, an alternative and effective treatment for Hodgkin’s disease. With radiation treatment, Jordan may be susceptible to developing another cancer later in life due to unintended DNA damage of healthy cells. Because the radiation therapy would be targeted at the tumors in his torso, he may also develop radiation fibrosis—permanent scarring caused by radiation treatment—which can lead to serious issues with his heart and lungs. The oncologist went on to speak about how there are several different combinations of chemotherapy medications that Jordan can take to treat his cancer; however, Dr. Andersen recommended either the ABVD combination or the Stanford V, because they are the most commonplace treatments for Hodgkin’s disease. “So what’s the difference?” Jordan inquired.

 The doctor explained that for each cycle of Stanford V, Jordan would be given different combinations of Doxorubicin, Bleomycin, Vinblastine, Mechlorethamine, Vincristine, and Etoposide intravenously every week for 12 weeks followed by radiation. He also explained that with each cycle of ABVD, Jordan would be given Adriamycin (Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine all at once, twice a month. In either treatment, Bleomycin and Doxorubicin are used as “antitumor antibiotics”—antibiotics that interfere with cellular DNA in order to disrupt cellular growth. Vinblastine is a plant alkaloid, and is effective in inhibiting microtubule growth in order to keep cancer cells from dividing. In Stanford V, Mechlorethamine acts as an alkylating agent by inhibiting transcription in cancer cells, Vincristine is a plant alkaloid , and Etoposide is both a plant alkaloid and topoisomerase II inhibitor which causes gaps to form in cancer cell DNA, thus stunting their ability to divide. In ABVD, Dacarbazine acts as an alkylating agent. Dr. Andersen pointed out that these chemotherapy regimens not only use very similar drugs, but studies have shown them to have statistically equal effectiveness in treating Hodgkin’s lymphoma in any stage for a wide demographic of patients(Figure 1) ,. With this in mind and because there are greater chances of developing long term side effects with the radiation that accompanies the Stanford V treatment2,3, and the fact that the treatment requires more time in the chemotherapy room, Dr. Andersen recommended Jordan take the ABVD regimen. 

<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;"> “Are the side effects bad?” asked Jordan. “The side effects are pretty standard,” Dr. Andersen responded. “You’ll definitely experience hair loss, nausea and vomiting are likely, and your blood cell counts may decrease, but we’ll test you frequently to make sure they don’t go too low. As for the nausea and vomiting, I will prescribe you anti-nausea medications as is standard for patients undergoing chemotherapy. If your white blood cell counts start to look low, I will prescribe some growth factors to you that will promote your bone marrow to produce more white blood cells. These are important in fighting infections; too low of a white blood cell count could compromise your immune system. Further tests for kidney, liver, heart, and lung function as well as blood cell counts will have to be done in order to establish a baseline so we can monitor potentially serious side effects as the treatment progresses<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;">. But since you are young and relatively healthy, your body should respond well to this treatment.” “How long will he need to undergo this treatment?” Jordan’s father asked. “Seeing as the cancer has spread from a lymph node under his arm to one in his chest, Jordan will likely need five or six cycles of this particular treatment.<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;"> ”

<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;"> Approximately three months after he was initially diagnosed with Hodgkin’s lymphoma, Jordan was half way through his third cycle of ABVD chemotherapy. Named for the combination of medications used in this treatment—Adriamycin, Bleomycin, Vinblastine, and Dacarbazine—ABDV is the most commonly used chemotherapy regimen for treating Hodgkin’s lymphoma<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;">. Despite standard side effects such as hair-loss and nausea, Jordan has responded well to his treatment. PET scans—radioactive medical imaging scans—of his torso conducted two months into his treatment have indicated that his tumors are shrinking; Jordan’s doctors are optimistic about his progress and estimate that he will only need two more cycles of chemotherapy after he completes his third. PET scans will be conducted again after his fourth round of treatment to confirm that the tumors are continuing to shrink. ABVD has been shown to be one of the most effective chemotherapy treatments for Hodgkin’s lymphoma. In addition, ABVD has less toxic side effects than other similar chemotherapy drug combinations The outlook for Jordan is great. The goal shifts from treating his cancer to curing it.

<span style="font-family: 'Times New Roman',serif; font-size: 13.3333px;"> During his last couple months of treatment, Jordan had become very curious about the disease he had, and how it was being treated. He spent his time connected to the IV bag researching how exactly the drugs that had been circulating through his body were shrinking his tumors. Jordan learned that chemotherapy drugs are delivered to cells through the circulatory system. In an effort to obtain the nutrients needed to sustain cellular growth, his tumor cells upregulated the vascular growth factor VEGF in order to promote angiogenesis—the growth of blood vessels from existing vessels. In creating these paths for nutrients, they were simultaneously creating a path for the chemo drugs to reach them. Jordan read about how Bleomycin and Doxorubicin—antitumor antibiotics—work by binding to and cleaving DNA in order to disrupt the cell cycle of the cancerous cells(Figure 2) He learned that Doxorubicin is also effective in inhibiting topoisomerase, an enzyme necessary for uncoiling DNA so it can be replicated. He also read about Vincristine—a plant alkaloid—that works by binding to tubulin dimers in order to prevent the formation of tubulin fibers (Figure 3). This prevents cellular division as tubulin fibers are necessary for maintaining the structure and fluidity needed for cells to divide. Vincristine is especially effective as it is more reactive with tubulin dimers than other plant alkaloids. Jordan also researched Dacarbazine—an alkylating agent—that works by binding DNA strands together, so they cannot be separated by DNA helicase and copied (Figure 3). After researching how the drugs in the ABVD treatment work, Jordan educated himself on his cancer.

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<span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> In researching Hodgkin’s disease, he discovered that the tumor cells primarily survive by evading cell death. He read one research article that describes how NF-kB transcription factors play a crucial role in controlling immune, inflammatory, and anti-apoptotic responses in B cells. The article describes how over expression of NF-kB transcription factors can lead to the synthesis of proteins that stop apoptotic—cell death—pathways. NF-kB can become over expressed in two main ways: through promotion by LMP-1 —an Epstein Barr Virus (EBV) protein—or by the degradation of IkBa which inhibits NF-kB. Jordan reasoned that his rogue B cell’s ability to evade cell death was likely due to LMP-1 from the latent EBV DNA that remained in his cells after he had mononucleosis, an infection caused by EBV. Another common observation in these tumor cells is the mutation of genes that code for Janus kinase (Jak). Jak activates transcription factors which can then enter a cell’s nucleus and promote the synthesis of inhibitors of apoptosis pathways. Jordan also read about how Hodgkin’s lymphoma tumor cells can resist cell death by manipulating their microenvironments. He read about studies that have shown that the tumor cells can recruit inflammatory cells to protect them and send them survival signals. Through proper positioning of these recruited cells, the tumor can also evade T cells and Natural Killer cells, thus avoiding direct attacks in addition to apoptotic pathways.

<span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> <span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> Jordan also researched how cells affected by Hodgkin’s lymphoma grow out of control. He discovered that the cancerous B cells primarily rely on the up-regulation of certain receptor tyrosine kinases—cellular receptors that are signaled by growth factors—including: PDGFRA, DDR2, MSPR, TRKA, and TRKB. No mutations in the genes coding for these growth factors have been discovered in Hodgins’s lymphoma tumor cells, so it is likely that their up-regulation is a result of autocrine or paracrine signaling .<span style="font-family: 'Times New Roman',serif; font-size: 10pt;">Therefore, the cancerous cells maximize the number of growth promoting signals they receive by signaling themselves or receiving signals from nearby cells to grow more receptors.

<span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> After researching his disease and how it was being treated, Jordan reasoned that the ABVD treatment was so successful for him because it targets the tumor cell’s ability to divide. He noticed that Hodgkin’s disease tumors are well equipped to evade apoptosis and attack by immune cells, but only one discovered way to sustain growth. Therefore, targeting the tumor cell’s ability to divide, through drugs that can sneak into the tumors through blood vessels, is an extremely effective treatment. Though none of the drugs used in the ABVD treatment target the specific receptors on the cancer cells that promote growth, inhibiting growth by targeting DNA and microtubule function is an effective way to exploit the fragility and sensitivity of Hodgkin’s lymphoma tumor cells.

<span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> “HIKE!” Jordan yelled as his center snapped him a football during practice. He shuffled back a few steps, scanned the field for an open receiver and launched the ball. Jordan’s eyes followed the spiraling football as it floated along a parabolic path into the hands of his teammate downfield. “That’s what I like to see!” shouted Coach Nelson from the sideline, “let’s break for water.” Jordan jogged off the field and pulled off his helmet. His once dirty-blond hair was coming in bleach blond. It was a year after Jordan had first noticed a small lump under his arm, and six months after he had started chemotherapy. The ABVD chemotherapy treatment recommended by Dr. Andersen had worked, and Jordan was in remission. After studying his disease and how he, his family, and his doctors combated it, Jordan had a sense that he had truly conquered it. He not only felt accomplished that he had survived cancer, but that he now understood it from both an academic and an experiential perspective.

<span style="font-family: 'Times New Roman',serif; font-size: 10pt;"> Apercu: In a battle with Hodgkin's lymphoma, the best defense truly is a good offense.