From our anonymous insider…
Leukemia/Lymphoma week. A spunky 40-year-old hematologist/oncologist hung up her phone as she arrived five minutes late for the first lecture. “Sorry! Sorry! My husband is incompetent at getting the children ready for school. I had to leave earlier than normal to get here. He can’t find my son’s shoes! The whole house is in chaos.” (She rejected three additional calls from the husband during the lecture.)
Leukemia, a cancer of bone marrow blood cells, is classified according to (1) stem cell lineage (myeloid versus lymphoid), and (2) chronic versus acute. Disease severity is determined by symptoms and the percentage of immature cells (called blasts) in the marrow and blood.
She began the lecture with an impassioned speech on the advances in treatment of chronic myelogenous leukemia (CML). “This is the coolest story of the century! It is an amazing time to be in medicine. In the 1990s, CML had 100 percent mortality within five years.” Dr. Brian Druker’s lab linked CML to the Philadelphia Chromosome, a translocation between chromosome 9 and chromosome 22 resulting in the constitutively (constantly) active BCR-ABL fusion protein. Druker developed imatinib, a targeted therapeutic agent, that inhibits the function of BCR-ABL protein. “This is what bench to bedside medicine is all about. Imatinib was the first successful targeted therapeutic in cancer treatment. The trials of the drug that became Gleevec showed complete hematologic response in 94 percent of patients versus 55 percent for standard of care. We never see these numbers. The coolest thing is it is a small pill. This is Nobel Prize-worthy.” The class, one week before exams and exhausted after three hours of lecture, showed little reaction. “Guys, come on, get excited!”
Imatinib is a nearly complete cure, with CML patients now as likely to live to a ripe old age as anyone else, but nobody wants to do a clinical trial investigating whether patients can stop taking Gleevec. “Would you sign up to be randomized to stop the drug that saved your life? Who is going to fund it? Not Novartis.”
She continued with the childhood disease of acute lymphocytic leukemia: “ALL is a parent’s worst nightmare. An 8-year-old falls on the playground and starts to complain of bone pain. When you go to the pediatrician, ALL is not on their radar. There is no fracture on x-ray, but the pain does not resolve.” After several tests including an abnormal CBC, the child is referred to a pediatric oncologist who then performs a bone marrow biopsy to diagnose ALL.
Induction therapy (initial treatment) involves 30 days of intense chemotherapy (typically, methotrexate) to get the child into remission. Due to ALL’s tendency to metastasize to the brain, chemo drugs are introduced via lumbar punctures every three days. “We fortunately have a fantastic prognosis for ALL. Children are resilient. We are able to use doses and treatment frequencies that are not achievable in adults.”
Lectures conclude with an overview of common chemotherapy agents and a discussion of side effects: “An overlooked area of chemotherapy is managing nausea. I had a patient vomit when she saw me at the grocery store. These drugs cause such visceral reactions. We’ve developed much better antiemetics in the last few decades.” She is a strong proponent of medical marijuana having trained in Seattle. “Even with the newer antiemetics, Marinol [synthetic THC] is one of the most effective agents I have seen to control nausea and appetite.”
We need to memorize the major complications of several drugs. Doxorubicin has a 11 percent risk of developing acute dilated cardiomyopathy. This rises to 35 percent if higher doses are used. Vincristine, a microtubule inhibitor, can disrupt the highway system of the neuron. This can lead to peripheral neuropathy (sharp pain in the extremities), one of the most common side effects of chemo. Certain breast and ovarian cancers requires hormonal agents. “Some of the estrogen modulators and aromatase inhibitor makes the patient feel like he or she is going through menopause. Testosterone inhibitors for prostate cancer causes this similar menopause sensation with hot flashes and all.” Straight-Shooter Sally: “All an oncologist does is hope the poison kills the cancer before the patient.”
Our patient case: George, a 31-year-old owner of a small construction firm, presents for a painless mass on the right side of his neck he noticed showering a week earlier. He has lost 10 pounds over the last month, which he attributes due to training for an upcoming bike race. He reports occasionally waking up sweaty in the middle of the night, which he attributes to anxiety from his 100-hour work week. He has intermittent back pain, which worsens when he consumes two or three beers. Physical exam reveals a 4 cm x 3 cm mass in the right supraclavicular fossa (space just above the collarbone) and an unbeknownst 5 cm x 5 cm mass in the right axilla (armpit). George undergoes a lymph node resection (removal). Biopsy reveals pathognomonic binucleate Reed-Sternberg cells on histology. George is diagnosed with Hodgkin lymphoma (formerly “Hodgkin’s lymphoma,” but the trend is to get rid of the apostrophe S when a disease is named after a physician who discovered it, as opposed to being named after a patient).
Hodgkin lymphoma begins in a single lymph node and, unlike other cancers that can pop up in random locations around the body, spreads along continuous lymph drainage, spreading first to the spleen, then the liver and finally the bone marrow. Most lymphomas afflict the elderly, but Hodgkin patients have a bimodal age distribution, peaking around 25 and 65.
George is joined by his oncologist, a 60-year-old with a slight stutter. “Oncologists are stereotyped as two-faced. We are aggressive in attacking the cancer, but the moment we give up on beating the cancer, we switch to palliative care. It could be overnight the day after receiving chemo.”
George: “I had chemo about once or twice a week for two months. Then I had a PET scan to re-evaluate.” His oncologist commented: ” George was a uniquely motivated patient. We discussed possible clinical trials. However, he wanted to preserve his lung function given his passion for biking. Clinical trials are not good for personalizing treatments. We customized a treatment regimen without standard-of-care Bleomycin.” [Bleomycin causes pulmonary fibrosis in 10 percent of patients.]
George was asked to describe the chemo center. “Chemo centers are a depressing sight. You remember the faces of the person next to you. I would try to imagine the life of the person. You can tell who will not be there next month.”
Mischievous Mary asked how George’s family managed the diagnosis and treatment. “My wife was a rock,” recounted a tearful George. “She would try to shield me. I remember one time I got up from the TV to do some task. My wife thought I would be away for 15 minutes. When I came back sooner, I found my wife and son scrubbing the whole room with bleach. I asked them, ‘What is going on?’ ‘Oh, nothing…’ they responded. I realized they were doing this out of fear I would get an infection.” He continued: “I kept working during the early chemo. After a few cycles it got unbearable to work immediately after a dose. I would take a few days off and lie in bed, then be back later in the week. My brother and his family moved into our house to help manage the business. I was upfront with my employees and clients. I am proud that not a single employee left.”
Type-A Anita asked what motivated George through his treatment. “I grew up without a father and did not plan to have children because I thought I wouldn’t make a good father. I am a Christian, but talk a lot with my neighbor who is a rabbi. One evening he told me, ‘Look at what you have accomplished.’ After that, I promised myself I would always be there for my children.”
Friday afternoon concludes with an introduction to intravenous catheters (IVs), the first workshop in our clinical procedure series to prepare us for clerkships. “Think of this as a little treat before you start exams next week,” explained the physician coordinating the series. Students have been eyeing each other’s veins all week, especially Buff Ben’s, a stereotypical class “orthopod” (aspiring orthopedist) who played baseball in college.
An ER nurse demonstrated IV insertion on a student. “The hardest part is getting the feel of advancing the catheter while retracting the needle. Access the vein by inserting the needle at 45 degrees. Once you see the flash [of blood], level out, inch forward with the needle and advance your catheter. If you lose the flash, pull the needle back and adjust.”
Students paired up and began. We adjusted… a lot. Gigolo Giorgio practiced on Particular Patrick, a fastidious and fashionable student from California. Giorgio did not level out enough and punctured the vein. He was moving the needle around aimlessly with a grimacing Patrick shaking under his dyed blonde hair (“flow” in California parlance, apparently). The ER nurse told him to just practice advancing the catheter. Patrick was not happy. “You are just shoving the catheter into my connective tissue!” Jane and I partnered. Neither of us got it. When I retracted my needle, blood gushed out. She now has a 3 cm diameter bruise from my handiwork. I snagged two unused IV kits to practice on at home under the guidance of Jane’s sister. Patrick: “We must look like heroin users.”
Our director of academic counseling emails a recipe for Goji Berry Trail Mix, including an explicit “place all ingredients in bowl and mix together” instruction in case any aspiring interventional radiologists are in doubt. We also learned about seven ways to calm our minds, e.g., reduce caffeine.
Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: none. Jane and I prepared for the weekend studying sprint by stopping at a craft beer and wine shop with a bar. We’ll be concentrating on lymphoma histology and the endless list of cancer drugs.
Can you call a 40 year old physician “spunky” without the thought police showing up these days?
May I never have cancer. I’m reminded of the saying that hospitals are where people go to die.