4 The Purgatory of the Hospital

with fearful trill

of the things unknown

but longed for still

—Maya Angelou, “Caged Bird,” 1983

I walked down the eight flights of stairs from the leukemia floor to the Skyway, a main drag connecting the sundry buildings of the sprawling Cleveland Clinic hospital complex. From there I would take another hallway leading to the outpatient cancer center, and then some stairs up to my office. On one side, I could stare out north, through the windows, in the direction of Lake Erie and the hospital’s semicircular main drive, to the new medical, dental, and nursing school building across Euclid Avenue. On the other side, I looked south at a large parking garage and the basic science research building, which houses laboratories, biomechanical engineering facilities, and even the front offices where the CEO and his staff work. The irony of having caged rodents in the research building, and my following this human habitrail of connections to my own nest, did not escape me.

As was true of the Mayo Clinic, the Cleveland Clinic hospital was born from war. George Washington Crile, MD, organized the American military hospital in Paris in 1915, later leading the US Army Base Hospital #4 in Rouen, France. Prior to serving overseas, Crile was in practice with Frank E. Bunts, MD, and Crile’s cousin William Lower, MD; both of them also served in the Rouen hospital. In France the three doctors discussed the creation of a new medical center in Cleveland, where they could continue to practice some of the military surgical procedures they were developing. John Phillips joined them in these discussions and in the eventual founding of the Cleveland Clinic upon their return.1

A four-story building, which housed all of the clinic’s 60 employees, was dedicated in February 1921. One of the Mayo brothers, William Benson Mayo, delivered the keynote address. The pale, brick edifice still stands today, though its original, large atrium has been turned into two floors. It is also easy to miss: the clinic’s footprint quickly expanded after opening with a new hospital building in 1924, and even-newer buildings surround and nearly engulf it now; major expansions in the 1950s, 1980s, and at the close of the last century have necessitated the Daedalus-inspired connectors through which I walk on a daily basis.

But in May 1929, only eight years after opening, the Cleveland Clinic almost came to an end when some nitrocellulose X-ray films ignited in the basement of one of its buildings. Nitrocellulose, the flexible film base first used in products made by the Eastman Kodak Company in 1889, had developed a reputation for being highly flammable and difficult to extinguish with water. The combination of the fire and toxic fumes from the films quickly spread throughout the hospital, leading to the deaths of 123 people, including patients, employees, visitors, and the hospital founder John Phillips. Victims were carried by stretcher, or even slung over the shoulders of volunteers, to be cared for on the front lawn of the hospital. After relocating temporarily to a nearby building, the clinic resumed patient care services five days later, and hasn’t closed since.2

The cause of the fire, though never precisely determined, was thought to have been due to a discarded match or cigarette, spontaneous combustion due to heat, or contact with a light-fixture cord near the films. The legacy of the blaze persists to this day: fire-fighting approaches, hospital procedures, and guidance on the proper storing of hazardous materials nationwide have been revised as a result of the fire, and all 50,000-plus employees at the clinic undergo extensive fire prevention and recognition training when we start our jobs, and we take refresher courses every year.

In 2017, the new Cleveland Clinic Taussig Cancer Center opened, a structure remarkable for its cantilevered glass facade, and for the clean white and gray interior walls interspersed with colorful artworks. If you troll the clinic’s Twitter feed frequently enough, you’ll see photos showing how the reflective glass of its exterior mirrors the sun and clouds in the sky to evoke a Magritte-like trompe l’oeil. Works featured in the building and on the entire hospital grounds number 6,500 paintings, photographs, sculptures, and mixed media installations or objects. Artists represented include Eva Rothschild, Rana Begum, and Spencer Finch, whose “Trying to Remember the Color of the Sky on That September Morning” is the only work of art to grace the National September 11 Memorial Museum. The Art Program at the clinic adheres to the belief that “fine art is good medicine,” in that it “comforts, elevates the spirit, and affirms life and hope.”3

The Boston-based William Rawn Associates designed the building, its focus on empathy for patients apparent even as the building was going up. Construction workers decorated a ribbon wall, each ribbon commemorating a loved one or family member of their own with cancer.4 Every day those workers walked by that wall, in their hard hats and bright orange vests, they must have been reminded who would be cared for within the completed structure, and what it was like when, as family member or friend, they sat by the infusion chair as the chemo dripped into a loved one. Before the last steel beam was placed, a bunch of us donned the same hats and vests and, using a silver Sharpie, wrote our names and a message to our patients on a girder. We all had something personal invested in that building, right down to its bones.

Similarly, when the new Dana-Farber Cancer Institute building was erected in Boston in 2016, construction workers there wrote the names of patients on the steel beams after seeing signs held aloft by children with cancer in the windows of the old building across the street. Another reminder of what was at stake within the confines of these spaces.

The newer buildings on campus evoke an antiseptic environment run by professionals, intended to inspire confidence in patients seeking treatment with us. With the new cancer building, I worried that the sterility of the surroundings would instead cause patients to think we were cold and indifferent, more of a business rather than a team of healthcare workers who care deeply about their patients. I was wrong, though—my patients repeatedly told me how much they loved the space, particularly the light streaming through the windows. In fact, when we participated in designing the building, we specified that the windows by the chemotherapy treatment rooms needed to be tinted, as many of the drugs we administer can make people more susceptible to sunburn.

When I am on service—taking care of people in the hospital—my office becomes no more than a closet, a place where I trade an outdoor jacket for a white coat in the morning, and a white coat for an outdoor jacket in the evening. One braces me against the elements of Cleveland weather, the other against bodily fluids. The first evening after meeting Joan and David, I grabbed my fall jacket and headed outside to the fresh air for the first time in 12 hours. As I crossed Carnegie Avenue to the parking garage, I saw the sun dip behind the downtown skyline. It was pretty, and sad at the same time, as my day had been bracketed by the sun’s rising and setting.

When I graduated medical school, I came in possession of the first car I ever owned—a late 1980s white Plymouth Turismo, passed down from a grandmother whose vision had so deteriorated that she’d been declared a driving menace. That dinged and dented car lasted for about three months before its transmission essentially exploded, and I had to get a new vehicle, fast.

Interns don’t have much in the way of leisure time, so I was only able to “shop around” at a nearby used car lot when I was post-call, having gone approximately 36 hours without any shuteye. In this state of sleep-deprived concupiscence, I decided it would be a great idea to buy a convertible.

In Boston. With winter approaching.

The car, a Honda Del Sol, performed admirably in October. But it fell a bit shy of expectations come February, when its light weight, low clearance, and dicey defroster frequently lost the battle against the heavy New England snow and the frustrated efforts of the Boston Public Works Department. Still, I adored that car, and every day the weather allowed, I would pop off its T-top for my drive home from the hospital. The cold Boston air was almost baptismal, allowing me to be cleansed daily of my own sometimes-thwarted efforts to clear the hospital roads of disease.

I never lost that almost physical need to be reborn at the end of the day. A few years after selling the Del Sol, I bought the car I always coveted in high school—a 1984 Porsche 911—on eBay, for a song. My family thought it was great. My in-laws, though, were aghast.

“How can you buy a car sight unseen, especially one from California?” my father-in-law demanded. He restored old cars as a hobby, and even paid for my wife’s college education with the proceeds from a 1940 Ford he made look new again. After I proposed to my wife, he had me drive her around in his 1929 Ford Model A, a test of my worthiness. He neglected to tell me the car had a reverse shift. Meanwhile, the route he “suggested” for us required me to make the car come to a complete stop while ascending the steepest hill in rural Greensburg, Pennsylvania, and then to get it going again. I passed, though just barely.

“A lot of people buy cars online now,” I told him. “I even had the seller take it to a garage, and the mechanic said it checked out fine.”

“Hunh!” he scoffed. “The mechanic is probably in cahoots with the guy.”

He and half the male population of Greensburg over the age of 70 were probably rooting against me, hoping that this car would be a lemon. But when it arrived it started right up, and never gave me a lick of trouble.

As my father-in-law’s best friend of more than 60 years put it, “It must be feel great to be young and stupid.”

Which passes for a compliment in those parts.

I got into the old Porsche and drove home, letting the Cleveland air work its magic. It wasn’t entirely successful, though. I felt guilty knowing I was tooling around in a convertible, while Joan and David wouldn’t breathe fresh air for weeks to come.

The next morning I was paged on the way to work by Karl from pathology. Always tricky to dial a phone while working a car’s stick shift, but Karl never paged just to chat about the latest research in the journal Blood. I called him back at the next red light.

“Hiya. Good news, I think this lady has APL,” he told me.

“Ms. Walker? Really? You have the FISH results back?”

Pennina Langer-Safer, M. Levine, and David Ward first developed FISH, or fluorescence in-situ hybridization, at Yale University in the early 1980s. With this test, a probe is manufactured to precisely fit a particular genetic abnormality within the chromosomes. Imagine a key that can only fit one genetic lock. Because these abnormalities are too small to be seen with the naked eye, even under a microscope, the probe is attached to a fluorescent marker that can be detected through the scope’s viewfinder. The good news about FISH is that it is so precise, it can detect one cell out of a thousand with that genetic abnormality. The bad news is that it can only detect the one abnormality for which it was constructed, and will not detect other genetic mutations.

“Not yet. We should have that this afternoon. But these promyelocytes are classic. I noticed her coags are off, too, and she’s got some schistocytes in her smear.” Schistocytes are red blood cells that look as if someone used shears to make the ends of the cell jagged. Karl, gentle as usual, was telling me she had DIC without making me feel bad, in case I had missed it.

“Nothing gets by you, Karl. Somebody paged me about that last night, and we’ve already given her some cryoprecipitate.” I replied, mentioning blood products that help restore the body’s clotting factors, which are consumed as part of DIC. “You sure enough about this diagnosis for us to start her on some ATRA?”

“I think that would be a good idea,” he answered. “We’ll know more later today.”

By this point I had reached the hospital. I parked, walked to my closet to exchange my outerwear for my white coat, and headed to the leukemia floor through my habitrail. Rachel was sitting at the nurse’s station by a computer.

“Did the lab call you?” she asked.

I nodded. “Looks like this may be your first patient with APL.”

“Awesome. Can you cosign the ATRA I ordered in the computer?” She never missed a beat.

I grabbed one of the WOWs, checked the dosing and schedule (twice a day, half the total dose in the morning, half in the evening, every day until she entered a remission, hopefully), and completed the order. “Let’s tell her the good news before the pills arrive.”

Joan was sitting in a chair by the door, reading The Plain Dealer. She glanced up at us as we walked in.

“Uh oh, it’s never a good sign when the two of you walk in,” she said, grimly. A spent bag of cryoprecipitate was still hanging on her IV pole, along with a bag of saline, and some zosyn, an antibiotic. She had spiked a fever, and not knowing whether it was due to the leukemia or to a brewing infection, we always played it safe and treated it as if it were infection. A couple of plastic caps from the ports on the IV lines were still lying on the floor. It had been a busy night for her. Behind her bed, a collection of menacing-looking connectors stuck out from the wall, labeled air, oxygen, and suction. Precautions? Or a herald of events not yet realized?

I smiled. “You know, we’re not always harbingers of doom. Sometimes we bring good news.”

A look of hope flashed across her face. “You mean I don’t have leukemia?”

I could have kicked myself for being sloppy with my language. Good news is relative: this sure as hell wasn’t good news compared to not having cancer.

“I’m sorry, you do have leukemia, that hasn’t changed. But it looks like you have the relatively good kind of leukemia, the APL we talked about last night. We’ll be 100 percent sure this afternoon.”

She processed what I said for a few seconds. “Of course, I knew I had those blasts and the high white blood count. How could I have been so dumb?”

I shook my head. “Not dumb, Joan, nobody would ever call you that. It’s just a lot of information, even for one of us to keep track of.”

She nodded and exhaled, giving herself permission to be human for the moment. “Okay, next steps?”

I told her about the ATRA and the FISH test. “And then we’ll start chemotherapy today, like we discussed.”

“Would you consider treating her with arsenic?” Rachel asked. Joan looked at her in horror, and then at me, as if wondering what had prompted me to invite this she-devil into her room.

But, as usual, Rachel had been doing her reading.

Arsenic compounds have been used medicinally in Eastern and Western medicine for almost 2,500 years. Hippocrates treated ulcers with the yellow sulfide of arsenic, also called orpiment or realgar. In traditional Chinese medicine, arsenous acid or arsenic trioxide paste was often applied to treat “tooth marrow disease.” Arsenic has been a treatment for the plague and malaria, and was used by Thomas Fowler at the end of the eighteenth century, in the form of potassium arsenite, to treat a variety of conditions, including rheumatism, epilepsy, hysteria, dropsy, heart palpitations, syphilis, ulcers, and cancer. In the nineteenth and early twentieth century, it was the standard therapy for syphilis, until it was replaced by penicillin. Well into the twentieth century, arsenic was even used to treat CML and Hodgkin lymphoma, after it was demonstrated in Boston in the 1880s that it could reduce high white blood cell counts.5

The empirical use of arsenic as an anti-leukemic agent continued in China during the past century. Then, in the late 1990s, Chinese investigators at the Harbin Medical University reported striking results when they treated APL patients with arsenic, absent additional chemotherapy: 73 percent of patients entered a remission, and even 50 percent of APL patients whose cancer had relapsed achieved this hallowed state. Around the same time, doctors in Shanghai reported similar results in patients whose APL had relapsed. Like ATRA, arsenic helps the leukemia cells stuck in primary school to mature and develop into high schoolers—healthy white blood cells. This led to a study in 40 patients treated with arsenic in the United States, all of whom had relapsed APL. Remarkably, 85 percent achieved normalization of blood counts and 86 percent even had disappearance of the translocation of chromosomes 15 and 17.6

As if the leukemia had never been there to start with.

Other studies were conducted in, of all places, resource-strapped India and Iran, where patients with a new diagnosis of life-threatening acute leukemia often had to wait days, at home, because no hospital bed was available for them.7 Medical arsenic, though, is cheap, and can be administered outside of the hospital, because it has few side effects—other than its name. Remissions were achieved in over 85 percent of patients, 65 percent of whom were still alive five years after their diagnosis. Patients in these countries who previously would have died from their leukemia instead were cured thanks to this old, scary-sounding drug.

Arsenic was approved in the year 2000 for the treatment of relapsed APL in the United States, based only on that 40-patient study, because the results were so remarkable.8 As occurs commonly with the introduction of new cancer drugs, studies start in patients who basically have no other options, and are the most desperate for a new therapy, and then are conducted in newly diagnosed patients, hopefully to prevent the cancer from ever recurring in the first place.

In the United States a nationwide study of almost 500 patients randomized them to receive arsenic, or not, following the initial round of aggressive inpatient chemotherapy (the cytarabine and daunorubicin). The investigators on that study found that patients who received the arsenic after they had achieved a remission from the chemotherapy were 20 percent more likely to be alive without the leukemia returning three years after their diagnosis than those who had not received the arsenic.9 This was the treatment approach we were proposing to Joan Walker.

Meanwhile, in an even bolder study, investigators led by Elihu Estey, MD, at the MD Anderson Cancer Center were eliminating the use of traditional chemotherapy altogether, treating lower-risk APL patients (frequently defined as those who had low white blood cell counts and relatively higher platelet counts) at diagnosis with just arsenic and ATRA. Of the 25 patients they treated, 24 achieved a remission.

Without a drop of chemotherapy.

German and Italian investigators, under the lead of Uwe Platzbecker, MD, and Francesco Lo-Coco, MD, picked up on this finding and conducted a study of 156 patients with lower-risk APL who were randomized to receive a regimen similar to what Estey had pioneered versus standard chemotherapy. They presented their findings at a plenary session of the American Society of Hematology in 2012 in Atlanta, Georgia, in front of almost 20,000 hematologists.10

The results? Not only was the combination of ATRA and arsenic at least as effective as standard chemotherapy; it was more effective, and caused patients to actually live longer than those treated with chemotherapy. All 77 patients receiving the arsenic and ATRA went into a remission, compared to 95 percent of those receiving chemotherapy. At two years following diagnosis, 99 percent of patients treated with the arsenic and ATRA were still alive, compared to 91 percent for those receiving chemotherapy.

When Platzbecker showed the results, first of the similar remission rates, and then a graph with the line indicating survival for those treated with just arsenic and ATRA hovering over the survival line for those treated with chemotherapy, an audible gasp went up in the audience, as those of us attending realized that our standard treatment for people with lower-risk APL had just changed.

Fittingly, when their publication of the study results appeared in the New England Journal of Medicine, Zhu Chen, who had done so much to make ATRA the standard therapy for APL, wrote the accompanying editorial.11

So, why not use arsenic along with the ATRA to treat Joan Walker? I explained some of this background information to Joan.

“Unfortunately, your white blood cell count was really high when it was measured down in Wooster, and your platelet count was low. Our labs have shown the same. You have what we would consider to be a higher-risk version of the leukemia, and just giving arsenic and ATRA may not be enough. We’ll need to give the chemotherapy along with the ATRA, and then, once you’re in remission, we’ll start the arsenic, as an outpatient.” Just like in the nationwide US study.

“My luck, having the high-risk good leukemia.” Joan shook her head, a gesture of incredulity. “Well, at least I have my health,” she said, wryly. We all sat in silence for a bit, as she continued to process what we had just discussed. “You did say remission, and that I would make it home.”

“That’s the goal. More likely than not, you’ll get there.”

“Promise?” she asked. Her eyes were both beseeching and commanding. Part patient, part OR nurse.

I hesitated, wanting to reassure her but also trying to be careful not to make absolute guarantees. “I promise we will do everything we can to get you through the chemo and then get you home.”

She continued to stare at me, making clear that what I had said wasn’t enough. I took a deep breath before continuing. “I promise we’ll get you into a remission and back home safely.” She nodded, sank back into her chair, and thanked us for seeing her.

Our conversation nagged at me, though.

I have been pushed by patients in the past to make promises—promises that they wouldn’t die in the hospital; promises that they would live long enough to see a grandchild born; promises of cure.

To become a doctor, I had to take about a gazillion standardized tests, in undergraduate and medical school, aptitude tests to get into those schools, three steps of medical boards tests, and two steps of specialty boards. As any grizzled test taker will tell you, when an answer to a multiple-choice question contains the word “always” (as in, “APL is always treated with chemotherapy”), that answer is invariably wrong.

Promises of a guaranteed medical outcome are a form of “always.” Add to this accumulating years of having seen the unexpected occur in patients, and it’s no wonder doctors and nurses are reticent to make promises we aren’t sure we can keep to our patients.12

On the other hand, I recalled a patient I met early in my career whose voice filled my small exam room with confidence and optimism. He was a large man, well over six-feet tall, and had been a scion in the business world, used to being in charge. After we discussed his leukemia diagnosis and treatment options, he put one of his large hands on my shoulder.

“Doc, I want to hear from you that you’re going to cure this thing and get me back to my family where I belong.

At the time I was taken aback, and tried to adjust his expectations, interjecting a series of caveats in an even, measured voice. He interrupted me.

“You’re not gettin’ it. I only want someone to treat me who is going to be fighting like hell, just like I am, and isn’t going to stop until this cancer is licked. I’m not hearing that from you.”

But I didn’t want to be the kind of doctor people talk about: not the one who tells people they are going to be alive in five years, yet they die two months later; and not the opposite—the one who tells people to get their affairs in order (right now!) only to be mocked when they breeze into his clinic two (or more) years later.

People want their doctors to be honest, but many also look for hope and confidence from them. I have tried to walk that line: between unabashed support for my patients, emanating from the compassionate part of me that aches to alleviate their fears; to reality checks about the grim statistics of the chances of curing their leukemias. Otherwise, how could they trust me to always tell them the truth?

But I haven’t always been successful.

Rachel and I joined the rest of the team, who were organized in an approximate scrum around the WOWs. We frequently debated what to call the lot of us. A pride, as with lions? Seemed over-confident, as did a shrewdness of apes. A murder, as with crows? Too ominous. Maybe we were like a flamboyance of flamingos. I looked over to the latest pair of post-call residents, who weren’t exactly looking flamboyant as they leaned against their WOWs to keep from toppling over. A gaggle—that felt right.

“How’s Mr. Sweeney doing?” I asked.

John, looking spiffy in a clean shirt and tie, had admitted David, and thus would follow him for the duration of his hospital stay or until John’s rotation ended—whichever came first. Frequently, our patients outlasted our residents.

“He had a pretty good night. Some nausea to the chemo, though, and his hemoglobin dipped to 7.8, so we’re giving him a transfusion today.”

“Did he throw up?” When John nodded I asked, “You gave him something extra for the nausea?”

“Compazine,” John answered. Embarrassing as it may be to admit, some say our greatest advances in treating leukemia over the past couple of decades haven’t been new chemotherapy drugs, but rather better nausea medication so patients better tolerate the chemotherapy we have; and better antibiotics, particularly antifungal medications, which reduce the number of people who die while their blood counts are low from life-threatening infections.

“Let’s go see him,” I said, as the gaggle of our team entered his room.

David was lying in bed, propped up on one elbow with his head swaying over a barf bucket. He looked miserable. Betty hadn’t arrived yet.

“I guess it would be foolish of me to ask how it’s going,” I said, as he glanced at us sideways. He gave us a half-hearted thumbs-up sign, the way football quarterbacks who’ve suffered a concussion signal the fans as they’re being carted off the field.

“We’re going to take care of the nausea,” I told him. I glanced up at his IV pole and saw the bag of red blood cells hanging. “We’re also giving you some blood, which I think will give you a little more energy.”

He nodded slightly, limiting his movements so he wouldn’t start retching again. “Just knock me out for the rest of it,” he whispered.

“I wish I could. You’ll sleep from the medications. I’m sorry about all of this, we’ll try to make it better.”

He nodded at us slightly again and closed his eyes as his nurse brought in a syringe filled with Compazine, and injected it into his IV line. We left quietly.

I worried about his becoming nauseated so soon after getting chemotherapy. Though I’d seen it happen before, and obviously it is a common side effect to the types of drugs we use to treat the leukemia, it was a bit unusual. Nausea can be complicated. Sometimes, when it’s like the “upset stomach” kind of nausea people get from eating food that doesn’t agree with them, it’s because the chemotherapy causes gastritis, an inflammation in the stomach. Other times it may be “the room is spinning” kind of nausea, like the feeling people get when they lie down in bed and close their eyes after a night of heavy drinking or following a particularly chaotic ride at the Cedar Point amusement park. In that case the chemotherapy affects their sense of balance, which the brain and nervous system control.

Nausea that is psychological comes in a couple of flavors. The first is anticipatory nausea, which patients may experience prior to receiving chemotherapy that has caused them to be nauseated in the past, or when encountering something they associate with nausea-inducing chemo. I heard about one patient who was successfully treated for Hodgkin lymphoma, which requires a chemotherapy regimen given every two weeks for four months. Every time she came to the cancer center, she threw up soon after receiving the chemo. Before long, she started throwing up in the car as soon as she saw the cancer center building, just anticipating how the chemo she was about to receive would make her sick.

Years later, after she was cured, this same woman was in the airport and happened to run into the oncologist who treated her. When the oncologist went over to greet her, she immediately threw up on his shirt, perhaps successfully fulfilling the wishes of many a cancer patient! The association hadn’t been extinguished, even years later.

Similarly, patients whose sense of smell is heightened due to chemotherapy have told me they can’t stand the “fragrance” of the antibacterial soap we use in our hospital. They associate it with their pre-chemo exam, performed of course with my freshly washed hands.

The other type of psychological nausea my patients have experienced relates to the five stages of grief described by Elizabeth Kübler-Ross in her landmark book On Death and Dying.13 People facing death—or as in the case of leukemia, any serious illness that represents the loss of health—progress on their way to accepting this new reality through a series of reactions that can occur in any order. These include sadness or depression, anger, bargaining, denial, and finally acceptance. Some people may not experience all or any of these stages. But because time is so truncated—from the point when a person first seeks medical attention for what seems like the flu, to the start of chemotherapy for leukemia—we often see patients march through at least some of these stages during their hospitalization.

Sadness may be obvious, especially in people who are tearful, and thus we keep a box of tissues close at hand at all times. But it may be subtler in those who withdraw from family and friends, or don’t engage in medical decision-making. Anger can be challenging: some patients will direct it toward themselves, as if they somehow could have prevented the leukemia from arising (“I should have gone to the doctor earlier!”); others will turn it toward their family, which causes predictable matrimonial discord or estrangement (“I told you to bring in my Cleveland Indians shirt, not my Cleveland Brown’s shirt!”); and others still toward current or past health care providers (“The food here stinks!” or “Why didn’t my primary care doctor find the leukemia at my appointment months ago?”).

Bargaining can be clear-cut (“God, if you help me get into remission, I will be a better Christian”). Or it may involve negotiation over tests or procedures (“I really don’t want to go for a CT scan today. How about we schedule one for tomorrow instead?”). Denial takes a number of forms, from doubting the diagnosis (“Can you repeat the bone marrow biopsy to make sure?”) to intractable nausea that can’t be relieved with medications—a subconscious, visceral reaction to the cancer diagnosis that a person may not be outwardly acknowledging but is nonetheless attempting to rid himself of. Depression can manifest itself in similar ways.

One of my patients, a woman in her late 20s with the same APL as Joan, was nauseated every day for the entire month she was hospitalized, and even after she was discharged to her home. We tried every nausea medication we had and engaged some of our specialists in palliative care to help; gastroenterologists then used a scope to see if there was a mechanical reason behind her nausea, but to no avail. Multiple times during that hospitalization, she asked us to repeat her bone marrow biopsy to confirm she had leukemia, even after we showed her print-outs of the biopsy reports that clearly stated: FINAL DIAGNOSIS: ACUTE PROMYELOCYTIC LEUKEMIA.

We eventually had to readmit her to the hospital because she couldn’t keep food down. Her mother, who cared for my patient’s 2-year-old daughter during her initial hospitalization, brought the girl in to visit during this second hospital admission. Perhaps it was her return to the hospital and the memories from her first stay. Maybe it was seeing her daughter run around that hospital room, and realizing just how much time she had just spent without her. But suddenly she burst into tears and sobbed unabated for the next hour. We witnessed in real time her psychological breakthrough as she progressed from denial of her leukemia diagnosis to acceptance. That night she ate everything on her hospital tray, and never had a twinge of nausea for the remainder of her therapy.

I remembered what Rachel had said about David: “It’s not right. He doesn’t want to be here. He doesn’t want to get the Ara-C and daunorubicin. He only agreed to it because his kids wanted him to be aggressive.” She was right. And with the nausea and vomiting, his body may have been agreeing with her assessment and revealing his true wishes about treatment.

We continued rounding for the next three hours, and then stopped in to see Joan as a team. Enough time had passed that her chemotherapy was already hanging from an IV pole when we entered her room. She was sitting in a chair, staring out the window, and barely turned around when we came in.

“How’s it going?” I asked as I snuck around her bed to try to make eye contact. She glanced over to me.

“It’s going.”

“Anything we can do for you?” I persisted.

She shook her head and turned back toward the window. Sadness.

Our final patient of the day was a 72-year-old man who had received the same chemotherapy regimen that David Sweeney was just starting. We tell people at the beginning of their hospitalization, as they are considering their treatment options, that with the 7+3, they can expect to spend between four and six weeks in the hospital, and he was coming hard on six. His blood counts showed no sign of recovery, and his bone marrow was a wasteland of emptiness.

We walked into his room, where his wife sat in a chair by his bed. Amazing how frequently this same picture is repeated in room after room. She gave us a half smirk as we glanced over to her husband, who lay in bed with the sheets pulled completely over his head and tucked underneath it, a life-sized, starched cocoon.

“Oh, that’s normal for him,” she told us. “On the ship, he had to sleep on a couch that was located directly under a vent. It was the only way he could keep warm.”14

The cocoon shifted as he heard us talking, and a hand emerged to pull down the sheet. He smiled sleepily at all of the eyes staring down at him, recognizing how silly he must have looked.

He was captain of a barge that hauled iron ore for the steel mills across the Great Lakes, at a time when steel mills were still open. (This is how the Steinbrenner family made enough money to buy the New York Yankees, when their attempts to buy the Cleveland Indians in 1972 were foiled.15) He steered these massive vessels from the back (“aft,” he liked to remind us landlubbers), staring out across a deck the equivalent of two baseball fields long.

“He’d be gone from March through October. I was one of the Lake widows!” She started to chortle but stopped herself, realizing how the leukemia could make that moniker all too real.

“That’s a long time to go without seeing each other,” I commented. “How did you get through it?”

“I missed her, but we’d meet up every month or two,” my patient said, sitting up in bed to join the conversation. “She would track the ship’s location.” I looked over to his wife for confirmation.

“I knew what day they would set out from Duluth, and approximately when they’d be getting into Chicago,” she said. “I’d pile the kids into the car and we’d go see him.”

“For how long?” I asked.

“A day, maybe longer if the ship had some maintenance issues,” my patient answered. “After the kids were out of the house, she’d join me for a week or two on the ship. That was better.”

His wife nodded but said nothing. A picture hung on the wall, of the sun rising over one of the Great Lakes. I imagined that was often the scene he woke to on his ship. We all stared at it for a few moments, before my patient sighed and asked if his blood counts had improved.

“Nope, not yet,” I answered. “Any day now.”

“It’s okay, we’re not in a hurry,” said this man used to waiting, used to the familiarity of one day looking much like the day before. Acceptance.

David’s nausea persisted, stubbornly, for the rest of his week of chemotherapy, while Joan’s sadness started to lift as more of her friends and colleagues streamed in. They were a funny bunch—aware of her impending alopecia, a group of nurses from the Wooster hospital had donned masks that made them look totally bald or like old men with grotesquely receding hairlines. Later, when Joan did lose her hair, a few actually shaved their heads in solidarity.

Joan’s children came to visit after school, often brought by friends or by the family they were now staying with. Joan did her best to show them she was the same mom as she had been two weeks earlier, before her diagnosis, teasing them and asking the same questions about the mundaneness of their daily lives as she would have over the dinner table. But despite their tough exteriors—her son’s tattoos on his arms and trucker’s cap, and her daughter’s multiple piercings—they looked scared, fragile even, like kids whose main source of stability was now broken.

On rounds a few mornings later, it was John’s turn to discuss Joan. He frowned a bit before starting.

“She had a rough night. She became short of breath, so we had to put her on oxygen. She also spiked a fever.”

“Did you get a chest X-ray?” Rachel asked.

John nodded. “It showed some patchy infiltrates, consistent with fluid overload from heart failure.” He turned his WOW computer screen toward me. Fluffy clouds floated over the gray background of her lungs. “So we diuresed her to take the fluid off and added vancomycin [an antibiotic] to her meds. But her oxygen requirements increased by morning, so we switched her from nasal canulae to a face mask. She’s now on 10 liters of O2.”

“Yikes,” I said. “Not good. How are her blood counts?”

He crinkled his nose. “That’s the weird thing. Her white blood cell count had been going down from the chemotherapy, but it suddenly spiked up today.”

I nodded. “Let’s start her on decadron 10 mg twice daily.”

John looked at me quizzically. “You thinking a COPD flare? I don’t think she’s a smoker.” Chronic obstructive pulmonary disease is often the end result of the havoc smoking wreaks on lung tissue. Sudden exacerbations are treated with steroids like decadron.

I shook my head. “Nope. And I’m not thinking heart failure either in someone this young without a history of heart disease.” I glanced over at Rachel, as a dawn of recognition spread across her face.

“This is differentiation syndrome, isn’t it?” she asked. I nodded. “She needs to be on steroids!”

“Wish I had thought of that,” I razzed her. “Let’s go check on Ms. Walker.”

When we walked into Joan’s room, I noticed a new photo now hanging on her wall, printed from someone’s computer; she was standing among her friends in her hospital room, laughing, the day they were all dressed in their bald wigs. Another photo, in a frame on her window seat, must have been taken a year or two ago; she was with her two children, all dressed up, at what looked like a wedding reception. A third photo by the window was a few years old: Joan with her surgical team.

I’ve long made it a habit to scan the walls of my patients’ rooms, to try to gain some insight into what their lives are like outside of the sterile confines of the hospital walls.16

Most are pasted with photos of family and friends, like Joan’s: significant events, like anniversaries or weddings; posed holiday photos, with matching outfits and frozen smiles; and my favorites, the casual or even goofy shots of my patients with full heads of hair, taken during a summer trip to the shore with their families, for instance, in which everyone looks tan and relaxed, or at a Halloween party, their smiles exaggerated to match their outfits.

I’ve cared for members of high school football teams or their coaches, whose walls are often adorned with large posters signed by all the players, or with photos of the team holding up signs saying “Kick leukemia’s butt!” When one high school football coach was being treated for leukemia, his family, friends, and team organized a fundraiser in which they sold rubber bracelets with his name on it; that year I saw Urban Meyer (who at the time was coaching at the University of Florida) wearing one at their national championship game.

Religion is a common theme, and patients often display crosses or St. Christopher’s medals in their rooms. Some turn to the religion of Marvel and DC Comics, pasting stickers of Batman, Ironman, Thor, Spiderman, and even the Teenage Mutant Ninja Turtle, Michelangelo, on their doors. I’ve seen them sporting Superman T-shirts, too—especially fitting given the Man of Steel’s “true” birth in 1933 at the hands of Jerry Siegel and Joe Shuster, two teenage boys from Cleveland’s East Side.

But most touching are pictures drawn by children or grandchildren, with bright yellow suns, electric green grasses, and rudimentary people, one always taller than the other. If I look closely, I notice the extra care given to drawing the smile, one as wide as can fit into the oval of the head—as if, with that smile, the child is willing a return to happiness, to how things were before the leukemia.

The love I see on the walls of those rooms is breathtaking, and a constant reminder of what my patients are trying to recapture. For those whose walls remain unadorned for the length of their hospital stay, though, I worry about the care they will receive when they are finally discharged from the hospital. We spend extra time with them when they leave, ensuring they will be safe.

Joan, lying in her hospital bed, looked quite different from the Joan in her photos.

She was laboring to breathe, with respirations at a rate of 30 or 40 per minute. I could see the muscles and tendons on her neck strain with the effort. Her face mask, attached to one of the projections marked “oxygen” coming out of the wall over her bed, was foggy with her breathing. She looked worse than I imagined.

“Joan,” I said, sitting on her bed and leaning in close to her face, so she could hear me over the flow of oxygen. “The chemotherapy we’re giving you, the ATRA, is working. It’s making the leukemia cells mature to normal white blood cells. But there’s a side effect. You have fluid in your lungs and you’re spiking fevers. It’s called differentiation syndrome.”

I looked her in the eyes but couldn’t tell if she understood me. All I saw was alarm, the kind that people display when they’re not getting enough oxygen and feel like they’re about to suffocate.

“Joan, you have fluid in your lungs from the ATRA. Do you understand me?”

She closed her eyes and nodded.

“We need to send you to the ICU so we can give you more oxygen, so you can make it through this.” As soon as I said this, out of the corner of my eye, I saw John and Rachel leave the room quickly.

Her eyes sprang open—more alarm. She shook her head. The ICU was her greatest fear.

“Joan, I think this is just temporary. We’re giving you steroids, and that’ll make it better, but it may take a couple of days for the steroids to kick in.”

She closed her eyes again and mouthed something to me, but I couldn’t hear it. I leaned in closer, lifted her face mask slightly, and asked her to repeat herself.

“Promise,” she whispered, between breaths. “You promised, go home.”

I lifted my face away. Her eyes were wide open.

“We’ll get you home.” I reassured her, but not confidently.

She held my gaze for a second, as if assessing my truthfulness, and shut her eyes again as the ICU staff entered her room. They rolled in a red “crash cart” that contained breathing tubes of various sizes, a defibrillator machine with paddles, IV lines and solutions, needles and catheters, cardiac medications, and all the ancillary equipment they might need to resuscitate a person in extremis. About 8 or 10 people accompanied the cart, swiftly doing what needed to be done. A few of them moved the bedside table and chairs away from her bed, and someone unlocked the brakes on the bed’s wheel to move it away from the wall so someone else could stand behind Joan, at the head of the bed, if it became necessary to place a breathing tube down her throat.

I hoped I was right.

Meanwhile, David was nearing the two-week mark since we had started his chemotherapy. His nausea had improved as he marched toward accepting his leukemia diagnosis, and the chemotherapy we had given to treat it. But also as a consequence of the chemotherapy his blood counts, low to start with, had taken a major hit. His total white blood cell count was now 0.3 (one-sixth of his baseline), his platelets were 8,000 (placing him at risk of spontaneous bleeding if we didn’t give him transfusions every other day), and he had become dependent on red blood cell transfusions every few days.

I entered David’s room and smiled at him and Betty as they sat side-by-side in chairs near the window. As usual, I glanced first at the photos and pictures decorating the sill. One was a shot of the family standing near a small grill in front of a tailgate setup: everyone wore Ohio State sweatshirts; David and Eric held beers.

“I’m sorry you’re going to miss the game this weekend,” I said to them.

David shrugged. “It’s okay. I told the kids to go and to text me updates. I tried to convince Betty to join them, too, and take a break from this place.”

She had been by his side every day, entering the Leukemia Unit and walking past our team’s gaggle each morning around 9, and heading back home after dinner. Like David, she seemed to have accepted his decision and dutifully recorded the details of our daily updates into her small notebook, in which she also wrote down questions from other family members. I couldn’t imagine what it must have been like for her, during the lonely drive to the hospital when she prepared herself mentally for the day to come, or during the even lonelier trip back home. Sometimes, she stayed at the guesthouse near the hospital, where family members of patients, or patients themselves with frequent outpatient appointments, temporarily reside. Alone at night, I wondered, was she imagining that this might be practice for widowhood?

Whenever a patient of mine dies, I send a note to the family, many of whom I have gotten to know pretty well. I use the occasion to reflect on how my patient affected me, and how much admiration I have for the often-inspiring way he or she lived with this contemptible disease. I also reflect on how lucky my patient was to have such a supportive partner, when that is the case. It isn’t always.

Occasionally, I’ll get a letter or phone call in return, in which the partner asks to meet with me.

It’s usually a wife, now a widow.

Often, the focus of these visits is the chance to ask “What if?”

“What if the cancer had been caught earlier?”

“What if he had chosen a different therapy?”

“What if the antibiotic had been started sooner?”

I never take these questions as an accusation of malpractice. Rather, they remind me of Joan Didion’s heroic exploration in her 2005 book The Year of Magical Thinking, where she reviews the details of her husband John Gregory Dunne’s cardiac arrest repeatedly, especially the report from the ambulance first responders.17 Her questions, and those my deceased patients’ partners, likely represent an iterative revisiting of events in the hope that doing so will change the inevitable outcome.

One of my patients, a minister, once observed that my role in people’s lives was pastoral. In that spirit, I tried to reassure these women: they had been exceptional partners, helping their husbands make good decisions and supporting them unfailingly, and they could not have altered fate.

I once met with a widow and her two children, aged 10 and 13 at the time. Their dad had a terrifically aggressive form of leukemia, and had died around Christmastime.

“We want to get some closure,” his wife told me. I asked the kids if they were okay coming to see me, or if they faced it with trepidation.

“We’re okay,” his daughter, the older of the two, answered. His son, a spitting image of my patient, was quiet.

I spoke to them as if I were talking to my own children, mentioning how much I liked their dad, and how I looked forward to seeing him and their mom. I told them what an awful disease he had, and how courageous he and all of them had been in facing it. I looked both kids in the eye and told them their dad talked about them all the time, and that he was so proud of them.

The son started weeping quietly, and wiped his eyes with the back of his hands. His mother rubbed his back gently.

“It’s okay to be a little bit relieved that your dad has died,” I reassured them. “Meaning that you don’t have to worry about him being sick and hear about leukemia every night.” The pastor in me tried to absolve. They nodded their understanding.

The four of us remained quiet for a bit. I noticed they were all tan and asked if they had gone on a trip recently.

My patient’s widow told me that, when he was dying, her husband had urged his family to go to Florida, to their usual spring break vacation spot, whether or not he could join them. They had honored this wish. She then told me a story about how, on their first night there, they discovered a bottle with a cork in it by the water, washed up on shore, “As if he had sent it to us.”

As a family, they wrote a letter to my patient, stuck it in the bottle and replaced the cork, and then my patient’s son threw it in the water.

But it came back. As if my patient were returning the bottle to them and asking, “Are you sure you’ll all be okay without me?” So his son threw the bottle in the water again.

“And this time it stayed,” the son told me, his sight set somewhere in the distance, picturing the beach, the heft of the bottle, the space where it once was.

I realized, at that moment, how worried I had been about them, and how much I, too, needed to be absolved by them for not being able to help him more.

“My place is here,” Betty said, smiling at me, and patting David’s hand.

“We’re doing this so I don’t have to miss any games next season, right?” David asked, taking her hand in his.

I nodded and gave him my non-answer. “That’s the goal.” I was still shaken from making my promise to Joan. “Speaking of which, I believe you have a date with a large needle tomorrow.”

Two weeks after starting an intensive chemotherapy regimen, we routinely perform another bone marrow biopsy to determine if the leukemia persists, because we can’t always tell from the blood counts. If we see enough blasts in the bone marrow, we give more of the same chemotherapy, hoping that will do the trick. If all we see is a vast wasteland—a bone marrow with few cells remaining because of the nuclear bomb of chemotherapy we used to level the landscape—we wait for the bone marrow, and blood counts, to recover on their own. When we started down this path, I had quoted to David a chance of going into remission of around 50 percent. If we had to retreat him, the likelihood that we would be successful dropped.

David grimaced as Betty took out her notebook and read over what she had written on one of the pages. “Oh yes, my secretary here has reminded me of that fact,” he said.

“Administrative assistant,” she corrected him. “When will we get the results back from the biopsy?” she asked.

“As early as tomorrow afternoon, but if the pathologists have to perform some additional tests, a day or two after that.” She recorded what I said.

“And then you’ll start more chemo?”

“As soon as we hear that leukemia is still there. If it is,” I added.

She wrote that down too.

The following morning, Rachel performed his bone marrow biopsy. Betty had come in early, so she could be there for him. I asked Rachel how it had gone.

“He asked me if we had a punch card, so that every time he underwent a bone marrow biopsy, he could get one free,” she answered. We all laughed—the BOGO (buy one, get one) nobody wants.

But we weren’t laughing that afternoon when my pager went off and Karl’s number appeared. It usually meant that the blasts persisted if results came back early. I gave him a call.

“Bad news,” he said. “Mr. Sweeney still has 20 percent blasts.”

“No need for additional tests to make sure?” I asked, half-heartedly. At this high a percentage, Karl was sure.

“Afraid not,” he answered.

I thanked Karl and hung up the phone. As I promised David, and every patient we treat, there would be no delay in letting him know the results, good, bad, or otherwise. I marched into his room, where he was lying in bed, wearing an “Old Guys Rule” T-shirt and reading on his iPad. Betty sat in her usual chair, completing a crossword puzzle.

“Hey,” I said to them as I walked over to sit at the edge of his bed. Betty, ever his protector, had her antennae up for danger. She had divined, either from my facial expression or from the unusual time of my visit, that information was about to be conveyed—information that would affect David’s course. She put the puzzle down and took out her notebook. We had started calling it “The Book of David.”

“What’s going on?” she asked, her pen poised for action.

“I got a call from pathology. Unfortunately, the leukemia hasn’t gone away, and we’re going to have to give you more chemotherapy to try to get rid of the few remaining cells,” I told them.

“How many are left?” David asked. I conveyed what Karl had told me. Betty flipped through her notes.

“He started with 42 percent. So that’s less than half.”

I nodded my agreement. “You’re spot-on. We’ve made some progress, but we need to get those blasts to less than 5 percent.”

“It’s good that his blasts have come down so much though, right?” Betty asked. “How does this affect his prognosis?” She persisted, looking quickly at David and then back to me.

My colleagues and I researched how this situation affected the prognosis in more than 1,500 people with AML who had been treated in studies conducted by one of the National Cancer Institute (NCI) cooperative groups—the Southwest Oncology Group.18

The concept of cooperative group trials came about in 1955, when the NCI formed a Clinical Studies Panel that concluded cancer research would progress faster if cancer centers worked together to enroll patients—particularly those with rare cancers—onto the same studies. Congress appropriated $5 million to the NCI to create the Chemotherapy National Service Center, which organized a number of these cooperative groups around the country. The trials that emerged from these groups set the standards for care for a variety of cancers and helped debunk the utility of particularly aggressive (and disfiguring) treatments such as radical mastectomy for breast cancer, or certain particularly aggressive chemotherapy regimens for lymphoma, which led to higher rates of infertility and secondary cancers—meaning, the lymphoma treatment led to the development of other cancers years later—but worked no better than standard regimens.19

A little more than one-third of the 1,500-plus AML patients were in the same tough spot as David—with more than 5 percent blasts two weeks into their treatment with cytarabine and daunorubicin. As it turns out, no single factor predicted the ability of someone with persistent leukemia to enter a remission subsequently—from the absolute percentage of blasts remaining in the bone marrow, to the percentage reduction in blasts from where they started, to a person’s age. Also, having persistent leukemia at this time point did not always portend a worse prognosis, but it exposed a person to risks associated with receiving more chemotherapy.

I communicated all of this to Betty and David. David still didn’t look pleased.

“So I’ll have to spend even more time in the hospital,” he said.

“I’m afraid so. We’ll give you another two days of the daunorubicin and five days of the cytarabine, and it’ll take longer for your blood counts to recover as a result. Figure at least an extra week, maybe more.”

David stared out the window, at the world he had left behind to receive this treatment that hadn’t worked yet, the world he wanted to return to. Had he rolled the dice and lost? Or was it another test of his mettle, of what he was willing to endure for his family?

Betty had stopped taking notes and crossed her hands over “The Book of David.” Staring at him, worry clouded her face. Would these be the last days together when they could still cling to a modicum of hope that the treatment would work? Or would it be one of the darkest hours they would look back on ruefully, years from now, when they knew that it had?