1 Leukemia Arrives by Dark of Night

I jumped up and shook hands with this man who’d just given me

something no one else on earth had ever given me

I may have even thanked him habit being so strong

—Raymond Carver, “What the Doctor Said,” 1989

Joan Walker was a surgical nurse in Wooster, Ohio, near Amish country, who couldn’t understand why she had become so tired every day, almost falling asleep on her feet while assisting doctors in the operating room.

“It felt like someone stuck a huge syringe into me and sucked out the energy, leaving me more tired than tired. I was a shell of a body, going through the motions of the day,” she later told me.

Wooster, located about 50 miles south of Cleveland in Wayne County, is typical of the state of Ohio in many ways. It is headquarters to businesses such as Daisy Brand, the maker of sour cream and cottage cheese, and the Wooster Brush Company, which manufactures paintbrushes and rollers. It is also an agricultural center that encourages its young residents to participate in 4-H programs and compete at the Wayne County Fair.1 As a result, industrial complexes and rural roads leading through bucolic farmland exist in equal measure. The patients Joan cared for reflected this balance, which she loved. Many, including Joan, had never left Wooster; their families, like hers, had lived in the area for generations and collectively pitched in to help raise the children. At the hospital, she often cared for her friends, and there were few secrets.

Perhaps it was years of waking up at 5 a.m. so she could be at the hospital on time for the first surgical case. Or the toll it took on her, being the single mom of two—a son who barely made it through high school and a difficult teenage daughter. It wasn’t just the tiredness: her gums started to bleed every time she brushed her teeth, and she developed a rash on her legs under the compression stockings surgical nurses wear to combat the swelling that comes with hours of standing in the operating room. When she mentioned these symptoms to the doctor she had worked with for more than a decade, he insisted she have her blood counts checked.

Early on a Wednesday morning, after the first surgical case of the day, she went to the hospital’s lab. With the technician who drew her blood, she joked about his ability to collect it on the first stick (he succeeded). After she had assisted on the second case of the day—a young man undergoing a hernia repair—the surgeon asked her to come into his office. He had just received a terrifying phone call from the lab.

Joan sat in a chair by the wall, still wearing her avocado-green scrubs. The surgeon sat in the chair behind his worn desk. Pictures of his wife and children adorned the walls, as did a photo of him with his surgical team, including Joan, taken a few years ago. She was still married back then, and was wearing her wedding ring.

She noticed his hair was mussed from the surgical caps he had been wearing all morning, and he made no effort to fix it. “Joan,” he said to her, “your tests came back, and they were pretty abnormal.” He grimaced and shook his head, clasping his hands in his lap as he leaned toward her. “I’ve never seen a white blood cell count this high. I need to get you over to someone who can figure out what’s going on.”

“How high?” she asked, looking her colleague in the eyes. Their professional relationship as doctor and nurse suddenly shifted; now, as doctor and patient, an unfamiliar vulnerability came into play for Joan, as it so often does when a healthcare worker gets sick.

“It’s 154,000.” They both knew that was over 15 times higher than normal. She swallowed the news and nodded her understanding.

“Do what you have to do,” she told him.

He picked up the phone, called the hospital operator at the Cleveland Clinic, the hospital where I work, and for the first time, she heard someone use the word leukemia when referring to her. The operator paged me, and I broke from rounds to answer her summons. That was the first time I heard about Joan.

I took out a blank 3×5 card from the pocket of my white coat and jotted down some notes: “48 yr old fem . . . 4 wks of fatigue . . . gum bld . . . wbc 150k . . . hgb 7.3 . . . plt 18.” The shorthand of illness. She was profoundly anemic, with a hemoglobin level that was about half normal, and her platelet count was one-tenth of where it should be, hence the bleeding.

“Yes, of course we’ll accept her to the leukemia service,” I told her doctor. He asked when she should leave for our hospital. “Today. If she would go home and pack her things and ask someone to drive her, that would be great.” He assured me that she would do that. We said our goodbyes, and I returned to continue my hospital rounds, anticipating her arrival sometime that afternoon.

Few cancers can be considered “good” cancers, but acute leukemia is worse than most. Whereas more common cancers, such as those involving the breast or prostate, can take years to grow to a size that can be detected, acute leukemia develops quickly, over just a few weeks, and thus cannot be screened for. Also, unlike those solid tumors in which cancer cells lump into a mass (it is estimated that it takes 10 billion cancer cells to form 1 cubic centimeter of tissue, the size detectable on a CT scan considered to be abnormal), leukemia is a “liquid” tumor, filling the bone marrow space as it grows out of control.

The first description of leukemia has been attributed to a French surgical anatomist, Dr. Alfred Velpeau, in 1827. He wrote about “a florist and seller of lemonade, ‘who had abandoned himself to the abuse of spirituous liquor and of women, without, however, becoming syphilitic.’” The patient had severe abdominal swelling, fever, headaches, and weakness, with an enormous liver and spleen, and pus-filled blood,” as he described it, “like gruel.”2

Despite Dr. Velpeau’s insinuations, “sin” does not actually cause the cancer.

Leukemia was first classified as a distinct medical entity in 1845. The British pathologist Dr. John Bennett described it in an autopsy report on a 28-year-old slater from Edinburgh. Six weeks later, in early 1846, Dr. Rudolf Virchow, a prolific German pathologist who wrote more than 2,000 scientific papers and books, reported it in an autopsy he had performed on a 50-year-old female cook with an excessive number of white blood cells. Virchow named the condition leukamie in 1847, combining the Greek words leukos (white) with aima (blood). He was also the first to conclude that cancer arose from otherwise normal cells and that inflammation played a role.3 There wouldn’t be even a marginally effective treatment for leukemia, though, for another century.

Leukemia cells proliferate in an unfettered fashion, making too many primitive, nonfunctional white blood cells while the normal bone marrow cells that make the red blood cells and platelets die out completely. Those leukemia cells get packed so tightly in the bone marrow, eventually filling almost 100 percent of the bone marrow space, that sometimes they can’t even be aspirated (sucked out) by one of our 4-inch-long, wide-bored bone marrow needles.

What results is a paradox of sorts: too many cells in the bone marrow but too few cells in the blood stream—except for the white blood cells, whose numbers may be sky-high.

Leukemia is also in some ways more insidious than other cancers in that the symptoms are subtle until they suddenly become life threatening. Normally, the white blood cell count is between 4,000 and 11,000 cells per microliter of fluid, the hemoglobin (a measure of the red blood cells) is between 11.5 and 15.5 grams per deciliter of fluid, and the platelets are between 150,000 and 400,000 cells per microliter of fluid. With the death of the normal bone marrow cells, the resulting low red-blood-cell count, or anemia—in Joan’s case a hemoglobin reading of 7.3 g/dL—causes people to feel tired, sleep more, and lose their appetite. The low platelets (18,000/µL for Joan) may cause minor bleeding from the gums or nose, or major bleeding leading to serious consequences, like a stroke, at lower levels. The high white-blood-cell count (154,000/µL for Joan), which can also occur with infections like the flu (though not nearly to as extreme a level as Joan’s), can cause fevers and chills. That is, in fact, what most people think they have—a bad case of the flu that doesn’t seem to go away.

That’s what Joan thought she had.

Imagine the shock when someone with acute leukemia goes to her doctor, or an urgent-care center, thinking she has the flu, and a doctor walks into the exam room and tells her no, she has leukemia, and must be admitted to the hospital immediately for treatment. It’s particularly daunting when that hospital is one of the largest in the world, almost 10 times the size of the hospital in Joan’s community, with almost 1,500 hospital beds, 225,000 hospital admissions each year, and over 6 million outpatient visits.4

Imagine the shock when I walk into that person’s room, trailed by a team that includes a hematology/oncology fellow, internal medicine residents, nurse practitioners, floor nurses, pharmacists, and students, and tell her that she needs to start chemotherapy within 24 hours, and may not survive the hospitalization. I would meet Joan later that day to have just that sort of conversation.

My team was waiting for me when I returned from answering the page.

“Sorry about that. Who’s our next patient?” I asked.

Two interns and two second-year (or “junior”) residents were standing in the hallway, each with a “workstation on wheels” (WOW), a laptop computer bolted to a platform that could be rolled from room to room. We document and store our patients’ medical records electronically, so we use the WOW to write daily progress notes, record vital signs, order medications, and request consultations from specialists. (These workstations used to be called “computers on wheels” or COWs. But rumor has it that one day a patient on the gastric-bypass surgery floor overheard a nurse refer to her COW and mistakenly concluded that he was the subject of her conversation. He took offense, and the name was changed.)

The interns, both guys, were dressed sharply in pressed white shirts and thin ties, while the two junior residents were in various states of bedraggled, the most extreme example being John, who had a two-day growth of beard and stained hospital scrubs. He was post-call, having just spent the night caring for our patients and admitting new ones. At least his counterpart, Becky, was wearing clean scrubs.

I could fool myself into thinking that the interns and residents loved learning how to treat people with leukemia as much as I did, but for many this rotation was akin to being sentenced to hard labor in the Gulag. Rumors about the leukemia service ran rampant—that rounds can last until late in the day (what I called “continuous infusion” rounding, like chemotherapy that is administered as a constant drip over a 24-hour period); that the patients could get desperately ill and commonly needed to be transferred to the intensive care unit; and that the emotional toll, from caring for people who seemed fine one day but could be on death’s door the next, was high.

All of that was true. But most interns and residents truly dreaded it because, despite the years they have spent in medical school learning about the science of disease and how we treat it, they still feared cancer. For some, it reminded them of their own family members who had cancer, endured toxic therapies, and still died. For others, they couldn’t shake the popular misconception that a cancer diagnosis was tantamount to a death sentence.

Many also resented that I peppered them with inquiries during rounds. I not only quizzed them about disease-specific data, but also asked them for details about their patients, which at first blush seemed to have little to do with leukemia.

What types of inquiries elicited such resentment, you might wonder?

First were the questions anyone might expect me to ask while teaching trainees about medical conditions they would soon be treating: the typical clinical presentation and how to make a diagnosis of leukemia; what causes leukemia and how to treat it; the population incidence and prevalence of the disease; and how to estimate prognosis. And then there were those other questions, the ones that focused on the stories about people who have just arrived at our hospital. John started to speak.

“Mr. Sweeney is a 68-year-old man with a history of hypertension and kidney stones who was in his usual state of health until two months ago, when he started experiencing fatigue and shortness of breath when climbing stairs. He went to his primary-care doctor, who sent him for an EKG and pulmonary-function tests, both of which were normal. She then ordered labs, which showed pancytopenia.” All of Mr. Sweeney’s blood counts—the red and white blood cells and platelets—were low.

“What were the exact numbers?” I asked.

“He had a hemoglobin of 8.2, platelet count of 73,000, and white blood cell count of 1.8.”

“Are you surprised that the white blood cell count was so low?” I followed up.

He thought about it for a few seconds. “No, because most older patients have a leukemia that probably evolved from another bone marrow problem.”

“That’s right.” I commended him. He smiled. “How do you know that he has leukemia based on those blood counts, though?” I asked.

“I don’t. But his primary-care doctor sent him to a hematologist, after scoping his GI tract to make sure he wasn’t anemic from a GI bleed. That was normal. The hematologist performed a bone marrow biopsy, and it showed leukemia.”

“What kind?” I inquired.

I was trying to get John to distinguish between the two acute forms of leukemia (acute myeloid leukemia, or AML, and acute lymphocytic leukemia, ALL) and the two chronic forms (chronic myeloid leukemia, CML, and chronic lymphocytic leukemia, CLL). Unlike acute leukemia, chronic leukemia can take years to develop and tends to be less life threatening—at first. Myeloid cells and lymphocytes are the two major branches of the immune system, with myeloid cells fighting bacterial infections, and lymphocytes fighting viruses. Table 1.1 includes basic facts about the different types of leukemia.

“It was AML,” John said, handing me a copy of the pathology report. I read portions of it aloud to the team:

“80 percent cellularity”—at his age, that should have been closer to 35 percent, or as a general rule, roughly 100 minus the patient’s age
“background of dysplasia”—as the resident indicated, this leukemia probably arose from a previous bone marrow cancer called myelodysplastic syndromes, in which the bone marrow cells are dysplastic (bad growing)
“42 percent myeloblasts”

Table 1.1

The Different Types of Leukemia 5

Type of Leukemia	Description	Number of Yearly Diagnoses (US, estimated)	Median Age at Diagnosis (years)	Treatment	Five-Year Survival
Acute Myeloid Leukemia (AML)	Cancer of the myeloid cells in the bone marrow; cells grow uncontrollably (proliferate) and stop maturing (blasts—comprising 20% or more of the bone marrow).	21,000	68	Intensive chemotherapy or Lower-dose chemotherapy or Watchful waiting Bone marrow transplant for high-risk AML or for relapse	30% (higher for good-risk features)
Acute Promyelocytic Leukemia (APL)	Subtype of AML in which the cells stop maturing at the “promyelocyte” stage.	1,000	50	Intensive chemotherapy and/or All-trans retinoic acid (ATRA) and arsenic trioxide Bone marrow transplant for relapsed APL	70% (trend improving with use of ATRA and arsenic)
Acute Lymphocytic Leukemia (ALL)	Cancer of the lymphoid cells in the bone marrow; cells grow uncontrollably (proliferate) and stop maturing (blasts—comprising 20% or more of the bone marrow).	6,000	16 (peaks in children and then again in older adults)	Intensive chemotherapy or Lower-dose chemotherapy or Watchful waiting Bone marrow transplant for high-risk ALL or for relapse	30% for adults (higher for good-risk features); 80–90% for children
Myelodysplastic Syndromes (MDS)	Cancer of the myeloid cells in the bone marrow; cells can be misshapen and grow uncontrollably (proliferate), and with advanced MDS stop maturing (blasts—comprising 19% or less of the bone marrow). Can transform to AML.	20,000	71	Lower-dose chemotherapy Bone marrow transplant for high-risk MDS or for relapse	30%
Chronic Myeloid Leukemia (CML)	Cancer of the myeloid cells in the bone marrow; in chronic phase CML, cells grow uncontrollably (proliferate) and with advanced CML stop maturing (blasts—comprising 19% or less of the bone marrow). Can transform to AML (called blast crisis CML).	9,000	65	Tyrosine kinase inhibitors (TKIs: imatinib, nilotinib, dasatinib, etc.)	70% (trend improving with use of TKIs)
Chronic Lymphocytic Leukemia (CLL)	Cancer of the lymphoid cells in the bone marrow; cells grow uncontrollably (proliferate) and with advanced CLL can transform to a large cell lymphoma or even ALL.	21,000	70	Lower-dose chemotherapy	85%

Myeloblasts, or just blasts, are primitive bone-marrow cells that eventually mature to become functional white blood cells. They are large, ugly, and menacing, particularly when they represent leukemia, and grow in sheets that seem to take over the other, normal bone marrow cells. Everyone has blasts in the bone marrow, but it is abnormal to have more than 5 percent of the bone-marrow contents consist of blasts. Once a person has 20 percent or more blasts, it indicates acute leukemia.

“What did Mr. Sweeney do for a living?” I asked next.

“He worked for a company that makes cardboard boxes.” John answered quickly, obviously forewarned that I always ask about my patients’ occupations. One colleague, a good friend of mine, wrote an essay about resilience in medicine, concluding that it boiled down to a “pathologic fascination with humanity.”6 I share that pathology—what buoys me is hearing about my patients’ symptoms, their fears, their children and grandchildren, their hobbies, and yes, their occupations.

“A cardboard-box company?” I looked up from taking notes. “How do you make a cardboard box?” John looked at Becky, and then at me uncertainly, trying to discern whether I actually wanted him to respond. Was I asking seriously, or just teasing?

I continued with the questions. “What was his job in the factory? Did he enjoy his work?”

“I have no idea.” This time, he answered a little more defensively. I couldn’t blame him. He was post-call, had barely slept, and I was asking him if his patient enjoyed this line of work?

“Okay, let’s rephrase the question. What was your worst job ever? And being an intern or resident doesn’t count.” The team laughed cautiously, and John looked at me, unsure again. Was he really supposed to answer?

Growing up in Rhode Island, I had my share of bad jobs. My first was at age 14 at a place called the Newport Creamery—basically, Friendly’s with a Rhode Island twist. I worked on the grill and as a busboy, filling orders and clearing tables as quickly as possible. I cleaned bathrooms, followed OSHA rules, and learned to treat customers with respect. Not a terrible job, but I didn’t have any basis for comparison.

The next year, I worked at a family-owned deli—that was a bad job. I even lied about my age so I could use the meat and cheese slicers, claiming I was 16. That was my first exposure to how dysfunctional staff can affect a workplace. The boss was moody, venting his anger by either insulting us or simply yelling. His wife, a mousy woman with a glass eye, did the accounting in the back room. The cook was addicted to cocaine and showed up sporadically. The boss’s son, who was a party animal in college and barely graduated, worked behind the counter, despite having promised himself for years that he would never work in the old man’s business. He had a tumultuous relationship with a woman who also worked behind the counter, and who would become unglued every time one of his former flames walked through the deli’s front door—which occurred approximately every other day.

But the worst part of the job involved being sent to grab some extra jars of borscht from the basement. I would open the door leading downstairs, brace myself, flick on the light switch—and the floor would seem to move as the massive infestation of roaches scurried for cover. But again I learned, this time about working with people who did not get along and about completing tasks you don’t particularly like, because it was my job. I also tried to see things from the boss’s perspective—I mean, the boss wasn’t exactly going to be like some Little Miss Sunshine, having worked in a disgusting deli his entire life.

Other jobs followed: many in food service but also as a truck driver, a maintenance man, and even in an ungodly hot warehouse at the peak of August. These jobs were not fun, but each gave me one more bit of knowledge about how a workplace functions, and how the things we take for granted are made. They also left me with a morbid curiosity about other people’s jobs, how businesses operate, and about the process for making everyday objects.

“The witness is asked to answer the question. What was your worst job ever?” I persisted with John.

We went around, and each member of the team contributed. I have asked this question multiple times. Many residents have worked in labs before. Some have worked in offices or for their parents. One woman worked at a restaurant in New Jersey, and we shared our common knowledge about grill cleaning: You take a piece of window screen patch and place it flat on the hot grill, holding the patch with a towel. You then pour seltzer water on the surface, and press down as hard as you can while scrubbing. If you slip, you burn your knuckles. (We both have the scars to prove it.) Another woman, an intern, had worked alongside migrant workers in Idaho picking raspberries, and she described her arms at the end of the day, blood-streaked from the thorns on the bushes. That sounded like a bad job. These last two were probably the best residents I have ever supervised.

And the worst? They were the ones for whom internship was their first job. They were the ones who didn’t understand why you have to check every lab, every vital sign, and every consultant’s note—the ones who didn’t understand that these tasks, as mundane as they are, actually have an impact on people’s lives. And that it’s their job to perform them.7

“Let’s go in and chat with Mr. Sweeney,” I suggested.

We walked into the hospital room. Mr. Sweeney was lying in bed, wearing a hospital gown patterned with the blue and green logo of our hospital. Diane von Furstenberg, who launched her brand in 1974 with a now-iconic wrap dress, had famously helped out with the design. He was slightly overweight, with a full head of hair, almost all salt with a dash of pepper. His legs were crossed causally, but his hand tapped the bed sheets nervously. A pole by his bed held a bag of saline, which dripped slowly through an IV in his arm. His wife sat in a chair by the window, in jeans and a scarlet and gray Ohio State sweatshirt. I introduced myself and asked each of the members of our team to introduce themselves. He asked me to call him David, and he introduced his wife, Betty.

“It’s nice to meet you, and I’m sorry about the circumstances under which we’re meeting,” I said, as I sat in a chair by his bed. He nodded grimly in agreement. “Where are you from?”

“Ashtabula. Near Erie.” Eastern part of the state, near the Pennsylvania border.

“Do you know why your doctor wanted you to be admitted to the hospital?”

“She wanted me to get treated for my condition,” he answered. This time I nodded.

“And what condition is that?” I asked. I did not intend to be mean or to patronize him. But occasionally, and as bizarre as this sounds, our newly arrived patients aren’t told that they have leukemia, but rather that they have a “blood” or “bone marrow” disorder. In one study we conducted, with almost 350 patients who had myelodysplastic syndromes, only 5 to 6 percent were told by their doctors that they had cancer or a condition similar to leukemia, whereas 80 percent were informed that they had a “blood condition”—despite the fact that their average survival was less than three years and most were treated with chemotherapy.8

David hesitated and glanced at his wife before saying the words. “Well, she says I have leukemia.” His hand tapped the sheets a little quicker, as his wife pursed her lips.

“It’s a scary word,” I acknowledged. Without realizing it he had been holding his breath. As he exhaled, nodding in agreement, Betty started to cry. One of the interns rushed to get her a box of tissues. “Do you know what leukemia is?”

“It’s a bone cancer,” he said.

“That’s right. Leukemia is a cancer of the bone marrow. Cancer involves the uncontrolled growth of cells. These cells acquire an abnormality that causes them to outgrow all of the normal cells around them. When this happens in the breast, a woman feels a lump. When it occurs in the lung, a person develops a mass that can be seen on an X-ray. The bone marrow is what I call a “high-rent district”—it can’t expand like breast or lung tissue, so when cancer grows in it, that space fills up pretty quickly.”

David was listening carefully as Betty put her tissue away, opened a small notebook, and prepared to take notes.

“Acute leukemia is unlike any other cancer in that two things actually happen: aside from the cells growing too fast, they also stop maturing. Imagine if the normal cells in your bone marrow started out as kindergarteners and keep maturing until they graduate high school, and then are pushed out into the blood stream to make a living as the white blood cells that fight infection, the red blood cells that deliver oxygen to the body’s tissues, and the platelets that stop bleeding. As acute leukemia grows, the normal cells die out, leaving only kindergarteners, because the cancer cells stop maturing. Just as you wouldn’t think that actual kindergarteners would function very well working in a factory or as carpenters, these cells can’t build the white or red blood cells, or platelets, that the body needs. We call those kindergarteners ‘blasts.’”

He nodded, recognizing the word from his hematologist’s explanation of his bone marrow biopsy results.

“So how do you treat it?” Betty asked, her pen poised over her notepad.

This was a complicated question, perhaps more so than she had anticipated.

The standard, intensive chemotherapy treatment for AML is called “7+3.” The “7” refers to the seven days of one chemotherapy drug, cytarabine, also called Ara-C, which was first isolated from Caribbean sponges and synthesized at the University of California, Berkeley, in 1959. It was approved by the FDA in 1969. The “3” refers to the three days of a second drug, daunorubicin, which derives from a microbe, Streptomyces peucetius, originally isolated from the soil surrounding a thirteenth-century castle (Castel del Monte) in Apulia, Italy, in the 1950s. The name daunorubicin is a combination of Dauni, a pre-Roman tribe that occupied the area where the compound was isolated; and rubis, which describes its red color. The FDA approved the drug in 1979.9

To understand how and why cytarabine and daunorubicin work, let’s go back to what many of us learned in high school biology about mitosis, and about how cells divide. Mitosis starts in the cell’s nucleus (its central portion) when DNA (the 23 pairs of chromosomes that are the blueprint for that particular cell’s function) replicates. As mitosis continues, the cell makes a perfect copy of itself, including the newly replicated chromosomes. For the cell to copy its DNA, it must first relax the tightly coiled structures of the chromosomes, using an enzyme called topoisomerase. After the DNA is copied, it will return to its coiled state.

Cytarabine acts like a Trojan Horse with its resemblance to cytosine deoxyribose, the sugar used to build DNA. When cytarabine is administered to a person with leukemia, it is incorporated into the DNA instead of the cytosine, blocking the cell’s ability to copy the DNA. (A cell that can’t copy its DNA can’t continue to grow and divide.) Cytarabine is given as a constant drip for 168 hours in a row. Daunorubicin, on the other hand, freezes the topoisomerase so the DNA cannot return to its coil, inhibiting the cell from copying itself. Daunorubicin is administered once daily as an intravenous “push” that lasts 10 minutes.

Cancer cells, by definition, divide and copy themselves much more frequently than normal cells. That makes them exquisitely sensitive to the chemotherapy, as they are constantly trying to replicate their DNA. But other cells in the body that divide and copy themselves with some regularity—such as hair and skin cells, and the cells in the GI tract that replenish themselves every time we eat—also become susceptible to the chemo. This explains many of the chemotherapy’s side effects: skin irritation and breakdown; hair loss; gastrointestinal events such as nausea, vomiting, diarrhea, and ulcers; and a precipitous drop in the blood counts (because the chemo also impairs the remaining normal bone marrow cells that continue to divide to make white and red blood cells and platelets). A person treated with 7+3 remains in the hospital for the seven days of chemotherapy, but also until the worst of the side effects have resolved—typically, for a total of a month or more.

The severity of the drug toxicities, and the body’s ability to recover from them, limit the amount of chemotherapy we can give. For serious conditions like acute leukemia, we accept a lot more risk than we would for, say, a drug to treat high blood pressure, because the downside to not treating acute leukemia is so extreme: certain death, on average within two months.

I explained the treatment, hospital stay, and side effects to the Sweeneys. The members of my team, who had already heard several similar conversations taking place with other patients during the past week, were shuffling, leaning against the hospital wall, and in general growing restless. Routine for them, anything but routine for the Sweeneys.

So much of medicine has become mechanized, from the treatment pathways we recommend for a given condition, to our reliance on electronic medical records. When I bring my own children to see their pediatrician, I often see more of her back and shoulders, as she pecks away at the computer in her examination room to complete her office notes about them, than I do her face. She’s under a lot of pressure, though, to complete those notes, or else she will have to take time away from her own children that night to finish them. One study found that primary care doctors spent almost 6 hours of an 11-hour workday populating information in the electronic medical record, 86 minutes of which was “pajama time”—after hours or at home.10

Facing someone with a new cancer diagnosis is different, though. Pathways make it easy to identify treatment options, and electronic medical records provide a simple way to order the right labs and prescribe the appropriate chemotherapy. But they can’t determine a patient’s goals, or read his body language.

“The chance that you could go into a remission, meaning we can’t find the leukemia as hard as we look, is around 50 percent,” I said. “But that isn’t the same as cure. We only know for sure that you’re cured of the leukemia when you come back to my outpatient clinic five years from now and it still hasn’t returned.”

Betty wrote down those numbers. “Then what’s the chance you can cure it?” she asked.

I looked over to David, meeting him in the eyes. “Are these numbers you’d like to hear, or would you rather I talk in generalities?”

He shifted his legs, glanced over to his wife, and then looked back at me. “Let’s hear it,” he said.

“The chance that we can cure this leukemia in someone over the age of 60 is less than 10 percent. That number is low, but real. I have some folks, now in their 70s and 80s, who I can say are cured.” I paused, letting the number sink in. David glanced down at his own hands as Betty wrote “<10%” in her notepad and then stopped writing, her eyes fixed on the pen still pressed to the paper.

“What’s the chance I don’t make it through this?” he asked.

“There are never guarantees,” I acknowledged. “Because the chemotherapy will lower your immune system and your platelets, you can have infections or bleeding events that could be life threatening. The likelihood that you could die from the chemo is between 10 and 15 percent.”

David mulled this over. “You’re saying that I’m just as likely to be cured of the leukemia as to die from the chemotherapy. But if I don’t take the chemo, then I’ll definitely die from the leukemia.” A statement, not a question. I nodded.

“It’s a trade-off,” I said. “You invest a month in the hospital, and risk dying, for a chance to live longer or even be cured. Or, you say to me, ‘thanks but no thanks, doc’ and leave the hospital, and we can give you lower-dose chemo as an outpatient or support you with blood and platelet transfusions, as you need them.”

“And that low-dose chemotherapy, can it cure him?” Betty asked. I shook my head.

“No. It has about a 15 to 20 percent chance of getting you into a remission. And the people who enter a remission—either with low-dose or intense chemotherapy—live longer than those who don’t go into a remission. But it isn’t curative.” She wrote down the numbers.

“This is a hard decision,” David commented. I wished I could have guided him better.

Unfortunately, the last time a clinical trial compared giving older adults intensive chemotherapy versus low-dose therapy or supportive care was in the late 1980s. Other studies—deemed “retrospective”—have looked back at how patients fared when treated with intensive or low-dose chemotherapy, but not as part of a formal trial. Those studies had mixed results, with some showing an advantage to intensive chemotherapy, and some showing no difference for intensive chemotherapy versus low-dose chemo or supportive care.11 The problem with those retrospective studies is what’s called a selection bias—that healthier patients were more likely to have been treated with intensive chemotherapy than unhealthy patients, and thus to have had a better outcome. The better outcome may have been because they were healthier to start with, and not because of any impact of the chemotherapy.

“Why don’t you take some time today to think it over?” I suggested. “There’s no wrong answer of what to choose—only what feels right to you, what your gut tells you.”

The Sweeneys nodded their agreement and thanked us for coming in. It always amazes me, how in this life-altering moment, my patients retain such kindness to be thankful when I have given them such rotten news. I rose from my chair to leave, but hesitated.

“I’m sorry, just one more question,” I said, as I motioned toward the post-call resident. “John tells me that you worked for a cardboard-box manufacturer.”

“That’s right, in a factory in Erie,” David replied.

“How many years?”

“Oh, goin’ on about 25 or 30. You don’t see many people sticking that long with a company anymore,” he reflected.

I agreed. “How exactly do you make a cardboard box?”

He shifted to sit up higher in his bed. “We make the cardboard itself out of wood pulp. Then the sides of the box are glued together using a starch,” he explained.

“Is that factory operational seven days a week?”

“Oh no,” he laughed. “There’s not that much of an urgent need for cardboard boxes! We were closed on the weekends. The problem was, that starch would go bad if it wasn’t used, so over the weekends, we added a preservative to the starch so it was still good on Monday.”

“Any idea what that preservative was made of?” I asked.

“Oh yeah,” David said. “It was made of formaldehyde.”

Formaldehyde. A known carcinogen linked to leukemia.12