by Michael LaPelusa
The dark coffee soaked through the fabric of my freshly pressed white coat. I grabbed a bleach pen and left my shabby studio apartment, hopped on my bike, and rode to the hospital. The automatic doors opened for me as I walked in. I navigated to the transplant ward physician workroom.
"Good afternoon!" the transplant oncology fellow, Dinesh Dang, joked. Scientific papers littered his workstation. A title slide on his computer monitor read, "Human Leukocyte Antigen Immuno-Editing as a Mechanism to Improve Donor Matching in Bone Marrow Stem Cell Transplantation.”
"Sorry I'm late! Coffee issues. My name is Lisa. I'm the resident on transplant this month. I look forward to learning a lot.”
"Happy to have you here. My name is Dinesh.”
"Oh, I know who you are," I blurted, tugging at my right ear. Playing with my earring, a gift from my mom, was a nervous tic. She got leukemia when I was in high school. Because her disease didn’t respond to chemotherapy, she underwent a bone marrow transplant. Unfortunately, the transplanted donor stem cells underwent a large-scale offensive against her tissues, thinking they were foreign. She subsequently spent the last months of her life suffering from “graft-versus-host disease” – a syndrome characterized by endless diarrhea, unrelenting fevers, and disfiguring rashes. As I watched my mom suffer and take her last agonal breaths, I decided to devote my life to medicine.
"I hope you’ve heard only good things. Are you interested in pursuing any particular fellowship after you finish residency?” Dinesh asked, trying to make small talk.
"I'm actually interested in transplant," I replied sheepishly. "Part of the reason I came to this residency program was because of your work," I went on, leaving out the bit about how I rejected my soon-to-be fiancée’s ultimatum to either stay together and complete residency near his family in the suburbs or break up so I could move to the city and continue chasing my dream.
"Right on. Meet me in the conference room before rounds," he replied.
Dinesh was a prodigy in the field of transplant. Rumor had it he was weighing several lucrative offers from large pharmaceutical companies to develop their research portfolios.
"Cool! Will do!" I blushed. I skipped to the nursing station and logged on to a computer to review patients’ charts.
"You're in my seat," someone squawked. It was Helen, the transplant ward charge nurse.
"Sorry, Helen!" I apologized. “I'll find another computer." I finished up and scampered from room to room to introduce myself to each patient, perform a brief physical examination, and talk to the bedside nurses. Afterward, I went to the conference room to meet Dinesh. The room was crowded. I sat in the back.
"Today, I’m going to tell you about our progress on immuno-editing in transplant,” Dinesh announced. He flashed a title slide on the screen – the same I saw on his workstation earlier.
“Preventing immune-mediated complications of transplant, such as graft-versus-host-disease, is a challenge. We rely on a national registry of bone marrow donors whose cells are analyzed to determine which alleles, or gene variants, they contain. Only half of all patients who require a transplant will have an available donor marrow with alleles that are, what we call, a perfect match. No perfectly matched donor marrows exist in the registry for the other unlucky half of patients, and consequently, they have a higher chance of developing graft-versus-host-disease. We think we can level the playing field with immuno-editing," Dinesh continued.
A flurry of whispers wafted through the room.
"Last year, we took bone marrow stem cells from a random group of mice. These mice served as bone marrow donors in our experiment. We immuno-edited their alleles to perfectly match the alleles of a second group of mice with leukemia. Next, we transfused the donor mice’s immuno-edited bone marrow stem cells into the recipient, leukemic mice. Not only did all the recipient mice survive, but not a single one developed graft-versus-host-disease. Our success led to funding – more than we asked for – to conduct a human trial. Let’s take a walk,” he gestured toward the door.
The group filed out of the conference room, nearly stumbling over each other in excitement. Dinesh led everyone down the ward to Bed 13.
"Three months ago, a young man went to his primary care physician because he was fatigued. Routine laboratory testing showed too many white blood cells and too few red blood cells and platelets. He was referred to an oncologist who identified cell surface markers consistent with acute myeloid leukemia – AML for short – using flow cytometry. The oncologist inserted a spiculated metal rod into the young man’s hip and sucked out bone marrow aspirate with a syringe. Then, the oncologist sent the aspirate to a pathologist, who, under a microscope, saw dysmorphic leukemia cells. Cytogenetic testing with immunohistochemistry staining, karyotyping, and fluorescence in situ hybridization revealed mutations in his DNA that indicated a poor prognosis unless he received a bone marrow transplant. Unfortunately, no perfect matches in the national registry existed. We approached the young man to query about participating in our immuno-editing trial.”
Dinesh waved to patient through the glass door, who returned the wave with a thumbs-up. He appeared shrunken in the bed, emaciated. I wondered if I was the only one who noticed how fragile he looked.
"Meet Adam, the first-ever human recipient of an immuno-edited bone marrow transplant,” Dinesh turned and looked at me. “Lisa, could you present this patient to the group?"
"Adam is 27 year-old male with AML now day four status-post immuno-edited bone marrow transplant. He had no subjective complaints this morning. He has been afebrile since transplant. On exam, I didn’t identify any pharyngeal edema, mucosal or skin lesions, lymphadenopathy, or splenomegaly. His labs are notable for the absence of anemia, leukopenia, or thrombocytopenia in addition to normal kidney and liver function. In summary, Adam’s blood counts are indicative of engraftment." Wow, I pulled that one out of my ass, I thought.
"That’s right. Today, we achieved engraftment of the first immuno-edited bone marrow stem cell transplant.”
The crowd was silent for a second, then burst into a round of applause.
“Great presentation, doctor.” I turned around and saw Dr. Martinez, my residency program director. “Presenting on the fly, in front of these bigwigs – that took guts. Keep it up!”
“Thanks, Dr. Martinez! It was nothing,” I replied. Impressing him was important. I was about to apply for entry into transplant oncology fellowship, and he was responsible for writing a letter of recommendation on my behalf.
Dinesh and I finished rounding on the rest of the patients in the transplant ward.
“Strong work today, Lisa. Let’s meet early tomorrow morning to talk about starting a new research project together,” Dinesh offered.
“That sounds awesome!” I gushed. “See you tomorrow!” I returned to the workroom and took a moment to reflect. Here I was, the first person in my family to graduate from college - not to mention graduate school and medical school – and I was treating a patient with an immuno-edited bone marrow transplant. My mom would’ve been proud.
I walked around the ward, stopping by each patient’s room to say good night. I ended with Adam. The lights in his room were out, but the television was on. Out of the corner of my eye, I saw an error message on the monitor displaying his vital signs.
“Hey, Adam!” I called. The pulse oximeter that was supposed to be recording his pulse was correctly attached to his finger, but no heart rate tracing appeared. I tapped his shoulder to wake him up. To my surprise, he didn’t.
“ADAM!” I shouted anxiously. I couldn’t tell if he was breathing. I touched my right index and middle fingers to his wrist. Oh, God. There was no pulse.
“CODE BLUE, BED 13” I yelled to the nursing station. Helen was there. Everyone in the ward immediately jumped into action. I stood at the head of Adam’s bed and assigned roles to everyone that came to help. Suddenly, Helen ran up to me and held a phone to my ear.
“STOP COMPRESSIONS!” a loud, shrill voice shrieked over the phone. “HE DOES NOT WANT TO BE RESUSCITATED!”
“It’s his wife,” said Helen.
“Can you pull up his chart and look for an advanced directive?” I asked.
“I do not want life-prolonging measures if my heart stops or I stop breathing,” she read. I stepped out of the room and called Dinesh.
“Hey, this is Dinesh”.
“Adam arrested. I don’t know what happened. He…” I stammered.
“I just saw him a few hours ago – he was fine. What happened?”.
“I don’t know! We started CPR and got his wife on the phone. She said he didn’t want to be resuscitated. We confirmed that with his advanced directive”.
“Keep resuscitating him,” Dinesh said.
“What?” I asked, unsure if I heard him correctly.
“Keep resuscitating him,” Dinesh repeated.
“Dinesh... he has an advanced directive that states he does NOT want to be resuscitated,” I tried to explain.
“If he dies, the most important experiment in the history of transplant will have failed. Funding for my research will evaporate, and patients who need immuno-edited transplants will die. It will be your fault.”
I stood there, dumbfounded.
“I will ruin you if he dies,” Dinesh threatened. The phone went dead.
I felt a pang of dread. After what seemed like an eternity but was probably more like a couple of minutes, an organized rhythm showed up on the cardiac telemetry monitor. I couldn’t believe it.
“I have a pulse,” cried a nurse. She held a doppler probe over Adam’s groin, superficial to his femoral artery. My instincts took over.
“Let’s prepare for intubation and central line placement,” I ordered.
The next few hours were a blur. Night turned to morning. I didn’t even get to go home to sleep before Dinesh walked into the workroom.
“Dinesh…” I began. He didn’t look up. Was he ignoring me? My phone rang. It was Dr. Martinez.
“H… Hi Dr. Martinez,” I stuttered.
“Hi, Lisa. Come to my office.” The call ended before I could ask why. I made the long walk through the hospital to his office and knocked on the door, holding my breath.
“Come in,” I heard. I opened the door and saw Dr. Martinez with a team of C-suite types. I recognized a few of them from rounds yesterday. Helen was there, too. I pulled at my earring violently.
“Adam’s wife informed legal that she’s filing a complaint and suing the hospital. Did you continue to resuscitate him after he went into cardiac arrest despite an advanced directive AND a plea from his next of kin to stop?” one of the suits asked. My eyes welled with tears. I nodded.
“Please leave your badge here, gather your personal belongings, and vacate the premises. It would be wise to obtain legal counsel,” another man stated. I took off my badge and put it on Dr. Martinez’s desk. Would I be stripped of my medical license? How was I going to afford next month’s rent? I slumped back to the workroom to grab my things. Dinesh was still there.
“Dinesh, I think I just got fired,” I wept. He didn’t look up.
“Dinesh, did you hear me? Aren’t you going to stick up for me?” I screamed desperately. “YOU WERE THE ONE WHO TOLD ME TO CONTINUE RESUSCITATING ADAM!”
He turned and looked at me, expressionless.
“I don’t know what you’re talking about.”
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