3 A Time for Decisions

For the yellow smoke that slides along the street,

Rubbing its back upon the window panes;

There will be time, there will be time

To prepare a face to meet the faces that you meet . . .

And time yet for a hundred indecisions

And for a hundred visions and revisions.

—T. S. Eliot, “The Love Song of J. Alfred Prufrock,” 1915

Most of the time our patients arrive on a stretcher, by dark of night, wearing another hospital’s gown. A phalanx of family members trails the stretcher, along with two emergency medical services technicians from the ambulance that brought our new patient to us. A cloud of shock, disbelief, trepidation, and sadness encircles the lot of them as they check in at the floor’s front desk and move en masse to the room where our patient, and scores of family and friends, will spend the next month.

But sometimes our patients arrive with less fanfare. Their registration at the front desk, a quiet formality, masks the seriousness of the diagnosis—and perhaps the depth of their despair at this new reality—which has turned their body into a sinister, unfriendly place.

Later in the afternoon, when Joan Walker arrived, she gave her information to Angela, the floor’s hospital unit secretary. Her new patient identification band noting her name, birthdate, medical record number, and unique QR code was now firmly in place on her left wrist. She was wearing jeans with brown leather clogs and a purple fleece jacket. Her best friend, also a surgical nurse, stood by her side and pulled Joan’s wheeled luggage behind her. The large black bag had a shock of red yarn tied to the handle, so Joan could identify it easily when it came off the conveyor belt at the airport. As she had packed her clothes earlier in the day, she recalled ruefully that the bag’s last trip was to Cancún. This would be no Mexican holiday, though she reminded herself that at least it would be all-inclusive.

“You wait right here, honey, and I’ll call your nurse,” Angela told her. Joan stood patiently, knowing the drill. Before long, a nurse who appeared to be a little older than Joan came up to her.

“Are you Joan? I’m Jane. It’s so nice to meet you.” She smiled warmly. Jane wore white pants and a white top, with white clogs. Her pockets were filled with pens, syringes, tape, alcohol swabs, and gauze pads—the trappings of a nurse who had been doing her job (and doing it extraordinarily well) for 25 years. Her hair was a reddish brown, and she sported gold-rimmed glasses. “Crazy Janey,” I called her, after the subject of Bruce Springsteen’s “Spirit in the Night.” But there was nothing crazy about Janey’s gut feelings when it came to her patients. You better believe that when Janey worried about a patient, I worried about a patient and directed the residents to check on that person more frequently. When Janey wondered if we should adjust a medication, I adjusted the medication. And when Janey told me she felt someone was coming out of the woods after being ill for days, I would start to breathe easier.

“I hear you’re a nurse down in Wooster.” She grasped Joan’s elbow and held onto it, both reassuring and steadying her, and held her gaze for a few seconds. That look said: “We’re both nurses. You should be the one escorting a patient to her room, not the one wearing the wristband. I’m going to help you get through this.”

Joan just nodded, her eyes misty, acknowledging the enormity of that moment, the awful irony, when caregiver becomes cared for.

It’s happened to all of us in healthcare, though in varying degrees of seriousness.1

A few years back, I was cycling on my road bike, training for a bicycle ride that raises money for our cancer center. As I headed down a steep hill, my bike started going pretty quickly: 20 miles per hour . . . 25 . . . 30 . . . 35 . . . when all of a sudden I hit a slick patch on the newly paved road and, as if pushed by some vengeful god, my bike slipped away from under me.

Slam! I hit the pavement so hard it took my breath away, with no time to even brace myself. The pain in my side was extreme, but I had the wherewithal to realize that at least I was conscious and able to feel pain. I also remembered that I was in the middle of the road and stood up so I wouldn’t get hit in the traffic.

That’s when the pain went from extreme to blinding, as I felt broken rib scrape against nearby broken rib. It wasn’t until later that I realized the distant, disembodied cry I heard was coming from me. I called my wife and asked her to pick me up, probably in some show of bravado that I really wasn’t battered enough to require an ambulance—which of course I did.

When my wife arrived, it took me a couple of minutes to figure out how I would fold myself into the passenger seat of her car. She drove to the nearby community hospital within our health system and dropped me off by the ER doors as she went to park. I clip-clopped in my biking shoes up to the triage desk and gave a breathless greeting to the nurse there.

“Hello there,” she answered. “And what happened to you?” she asked, scanning my torn cycling jersey, bloody shoulder and leg, and awkward stance.

“I was biking . . .” breath, breath, “. . . and the bike slipped . . .” breath, breath, “. . . and I fell.”

“Ouch. Well, sit down in this chair so I can get your vital signs.” She gestured toward a blue plastic chair by her desk. I looked at her uncertainly.

“I don’t think . . .” breath, breath, “. . . I can sit.”

She looked at me quizzically and walked around the desk to stand next to me. “How fast were you going on this bike?” she asked.

“About 30 . . .” breath, breath, “. . . maybe 35 miles per hour.”

She shook her head pityingly and took hold of my elbow, just as Janey had done with Joan. “Oh honey, come walk with me to the other side of the ER. You’re a trauma.”

She gently led me away from the minor and major medical portion of the ER, never letting go of my arm. When we reached one of the trauma bays, she stopped.

“Now, I’m going to have to call a code for you, and a lot of people are going to come running down here when I do. Why don’t I help you off with your clothes, because otherwise they’re going to cut them off with trauma scissors.” Her kindness was in such contrast to the brutality of the crash, to the unforgiving pain I was feeling, it brought me to tears. Just like Joan.

I nodded my agreement, and she pulled off my shoes, biking pants, and what was left of my shirt, and slipped my arms through the hospital gown sleeves. My transformation was complete—I had become a patient. She eased me on to the stretcher, and chaos erupted as people ran into the bay.

It’s at this point that, as a doctor-cum-patient, I tried to make the calculation of whether or not to tell the healthcare workers now tending to me that I was “in the biz.” On the plus side, I might be treated like a VIP. On the minus side, I might be treated like a VIP.

Having VIP status in a hospital is not all it’s cracked up to be. True, these patients do get to occupy nicer rooms on quieter floors, closer in appearance to a fancy hotel. Which sounds great, except these floors are not disease-specific, and the nurses, doctors, and pharmacists who provide the care may not be specialized in the illness that required the hospitalization.

Doctors and nurses who care for someone labeled “VIP,” especially when that VIP is also a medical professional, tend to get more nervous because the number of people scrutinizing their every move will probably be greater than on average. As a result, the likelihood increases that mistakes will be made. The number of consultants involved also increases with efforts to avoid those mistakes, as do the numbers of laboratory and radiology tests.

When I was an intern, I cared for a famous infectious disease specialist who, ironically, had developed an infection requiring intravenous antibiotics. I quickly wrote the order, so he wouldn’t have to wait to be treated—but the dose I wrote was twice what was standard. He was the one who caught the mistake just as the antibiotic was being hung by his bed. I slowly walked into his room, tail between my legs, ready to be chewed out for my carelessness. He just laughed, and generously said that he assumed I had tried the higher dose based on a recent study.

So now, having to make a quick decision, I decided to keep it on the down low that I was a doctor. Which lasted for all of about 10 minutes, by which point the nurse had noticed the Fitbit I was wearing to track my activity—the same Fitbit worn by other employees in our health system, so we could qualify for discounts on our health insurance. Sure enough, after X-rays confirmed multiple broken ribs and a pneumothorax (which explained my breathlessness), I was given a private room, visited by a bevy of consultants, and underwent a lot of tests.

On the one hand I appreciated the attention. But I wondered how much of my care was ordinary, and how much extraordinary. It also quickly became apparent how awkward it would be to refuse the recommendations of those in my profession. I didn’t want to be known as a “difficult patient” or an “ungrateful colleague.”

On the other hand, in situations where my workplace status wasn’t known, how enlightening to view the hospital from a patient’s perspective. When the transport guy (who must have been popular) wheeled me down to the radiology department the following morning, a Monday, multiple hospital employees stopped him to chat about their weekends. The aroma from the Starbucks cup each of them gripped was robust, and in stark contrast to the anemic cup of brown liquid that had graced my hospital tray just minutes earlier. I tried to look them in the eye and nod a hello, as I would have at my own hospital. I had learned to do that when I moved to the Midwest (where lack of such greetings are associated with anger) from the East Coast (where such regular greetings to strangers might have earned me a reputation of being needy or even unhinged). But I was ignored, just an object on a wheelchair. I vowed that none of my own patients would ever feel so marginalized, so like an outsider, when their illness prevented them from participating in the normal interactions enjoyed by those caring for them.

Janey walked Joan into her room to do intake and get her settled, and Rachel followed them soon after, a bone marrow biopsy kit in her hands. Great—the sooner the biopsy is completed, and a bone marrow sample makes it down to Karl, the sooner we can have a diagnosis and get started on treatment.

Why do we rush people to make decisions about treatment for acute leukemia, often within a day or two of their diagnosis? At first blush, it seems unfair. After all, a woman who eventually is diagnosed with breast cancer that requires chemotherapy may have weeks to consider her options: from the moment she first feels a breast lump while taking a shower; to the time it takes to schedule an appointment with her primary care physician, who confirms that a worrisome lump is present; to the next step of undergoing a confirmatory mammogram or ultrasound; to scheduling a surgical biopsy; to waiting for the pathology results to return; to finally meeting with an oncologist to discuss medical, radiation, and/or surgical treatments.

Unlike breast cancer though, leukemia profoundly affects not only the platelets, and thus the body’s ability to stop bleeding, but also the immune system, leaving a person susceptible to life-threatening infections. While Joan had a white blood cell count of 154,000, most of those were probably blasts—the kindergarten cells—and it was really remarkable that she hadn’t already caught a devastating cold.

But the clock was ticking. At any moment she could contract an infection that would run rampant through her defenseless body, or she could all of a sudden start to bleed internally. We needed to stop this malignant golem before it killed her.

Theoretically, then, it makes sense to diagnose and treat acute leukemia rapidly. But is there a way to prove it? Along with colleagues at the MD Anderson Cancer Center in Texas, my Cleveland Clinic colleagues and I examined over 1,300 people diagnosed with AML at both of our institutions over a 10-year period.2 Everyone was treated with an intensive chemotherapy regimen, similar to what I described to David and Betty Sweeney. We measured the time from when a leukemia diagnosis was made to when chemotherapy was started, to see if delays in starting treatment mattered.

What we found was fascinating.

For younger adults, defined in the study as ages 17 to 59 years, treatment delays mattered—a lot. Longer times from diagnosis to starting therapy were significantly associated with a lower chance of entering a remission, and a lower survival rate. With every day that passed, the chance that we could successfully treat a person’s leukemia diminished substantially—by almost 10 percent going from a one-day delay to a five-day delay. That’s the reason Rachel trailed Joan and Janey into the room to perform Joan’s bone marrow biopsy.

But for adults 60 years and older, delays didn’t significantly impact remission rates or survival. We hypothesized that older adults with AML did better with delays because, for many, their leukemia evolved from a previous bone marrow disorder like myelodysplastic syndromes, which we suspected in David. Rather than a dramatic change that caused leukemia to grow and cause symptoms, as commonly occurs in younger adults, for older folks the leukemia was more of a slippery slide from a previous condition that may have existed for months or even years, and was therefore not as life threatening.

Still, we didn’t draw an arbitrary line in the sand at age 60 for whether we would hustle to start therapy or not. For some older adults, the time from diagnosis to starting chemotherapy did matter, if not biologically, certainly psychologically.

I walked over to David’s room to see how he was doing. He was still lying in bed, watching the news on the small, flat-screen TV hanging on the wall. I watched him for a minute from the hallway. He held the remote in mid air, as if about to change the channel, but he didn’t click it. He was watching, but not watching, distracted, his mind elsewhere. Betty sat in the same chair she had occupied earlier, a crossword puzzle book open on the bedside table, which she had pulled in front of her. She was using the small golf pencil the hospital provided to every patient to take notes and fill out menu choices. I knocked softly at the open door before entering. They both looked up.

“Anything exciting going on in the world today?” I asked him.

David smiled a bit and shrugged his shoulders. “Oh, you know, crime and politics,” he said, vaguely. Betty put her book down.

“And Ohio State football,” I offered. “You think they’re headed to the National Championship?”

This time Betty smiled. “We put both of our children through Ohio State. They get alumni tickets to the games. In fact, we’re planning on going to the Horseshoe in a couple of weeks.” A look of uncertainty flickered across her face as she realized mid-sentence that David’s future, their future, and the chances that he would be making it to the stadium in two weeks were slim.

“About that,” I said, as I sat in a chair by David’s bed. “Have you made any decisions about your leukemia?”

“We’ve talked about it.” He glanced over to Betty, who was staring at him, nodding her head faintly. “And I’m not sure it’s worth going through all of this, with the aggressive therapy, being cooped up in the hospital and away from family, getting sick, maybe even dying, for such a low chance of being cured. I’d rather take the low-dose stuff and sleep in my own bed every night.”

I turned to Betty. “How do you feel about his decision?”

“I’ll support whatever he wants to do,” she said bravely. David reached over to hold her hand. As she started to cry, he did, too. I grabbed the tissue box from the window seat and brought it to them. I was about to sit back down when a man and woman, both a decade or so younger than me, entered the room. They wore leather jackets, his brown and hers black. She sported an Ohio State scarf around her neck. David introduced them as Eric and Susan, his and Betty’s children.

“Can you explain to them what’s going on with David?” Betty asked me. Eric walked over by his mom and leaned against the window seat. Susan sat on the bed by her dad.

I reviewed much of what I discussed earlier in the day about David’s diagnosis and treatment options, along with the chances the therapies would work. As I spoke, Susan gave her dad quick glances, checking to see how he reacted to my description. They seemed close. When I finished talking, Eric piped up.

“When can you get started on the hospital chemo?” he asked.

David cleared his throat. “I’m not sure I want to go that route. I’m thinking of taking the other drug that I can get in the doctor’s clinic.”

Eric popped up from the window seat. “Dad, you can’t do that!” he exclaimed. “Your only chance of beating this is by getting the high-dose chemo. The doctor says it has a good chance of working. You can’t just give up like this.”

“He’s not giving up,” Betty countered. “And the doctor said he only had a 50/50 shot with that chemo. And he could die getting it.”

“Well, he’ll die if he doesn’t get it,” Eric answered, and crossed his arms.

“Dad’s thought about this carefully, Eric,” Betty said. “He doesn’t want to be cooped up in the hospital for a month.”

“If I’m going to die, I want to die in my own bed,” David said quietly.

Susan had placed her hand on David’s leg and was looking at him intently. “Daddy, we want you around,” she said. “I’m not ready to let you go.” She started crying, and David’s face collapsed into tears.

“Why don’t you all talk this over a bit and I can come back,” I said, unnecessarily. At that moment, I was the least important person in the room.

How people make decisions about treating their cancers is complicated. One reason is that both patients—and doctors—exaggerate the benefits of interventions and minimize the harms. In one systematic review of 35 studies that enrolled over 27,000 patients, most participants overestimated benefit for 65 percent of outcomes, and underestimated harm for 67 percent.3 These studies included interventions like mammography or colonoscopy screening for breast and colon cancer, or mastectomy to prevent breast cancer.

Doctors don’t fare much better. In another systematic review of 48 studies that included more than 13,000 clinicians, some of which asked about benefits of cancer screening or risks of cancer from other interventions such as radiation exposure associated with CT scans, more than half the participants overestimated benefits, and underestimated harm, for almost one-third of outcomes.4 The authors of these studies speculated that such unrealistic optimism stems from core psychological needs such as hope, safety, a sense of control, the need for action, and even reassurance that the right decision has been made. Add to this the clinicians’ conviction that they need to act when tragedy strikes—tragedy, in this case, being cancer.

One of my favorite sayings in medicine is “Don’t just do something—stand there!” The hardest decision I ever have to make is to not test or treat a patient, or to be comfortable offering a “no therapy” option to someone like David Sweeney, and to be genuinely supportive if that’s the route the patient decides to go.

After all, I haven’t lived the same life David has. Thus, I can’t know what factors he uses to weigh risks and benefits or how to assess the influence of people he holds dear in his life.

I once took care of an Amish man, from a town not too far from where Joan lived, whose white beard made him look much older than his 50 years. Like David, he had acute leukemia, and I had a discussion about treatment options with him similar to the one I had with David and Betty. The difference, because of his younger age, was in the estimates I gave him for going into a remission (about 20 percent higher), death from the treatment (about 10 percent lower), and chance of being cured (about 30 percent higher).

“What if I chose to leave the hospital without treatment and go back home?” he asked me.

Given his age, I was a bit surprised that he wanted to consider this option.

He explained to me that he was a deacon in his community and was privy to the hospital bills that resulted when other members had become ill. Many Amish don’t have private insurance, but as a community they pool their resources to pay the bills. He didn’t want to cripple others financially to pay for his healthcare.

As he put it, “This world is not my final destiny, anyway.”5

Another patient, a man in his 60s, had a leukemia that kept returning, despite our best efforts at containing it. He and his wife made the regular hour-and-a-half drive to my clinic in their aging car, which itself had become less and less dependable. When I broached the topic of another round of therapy, a pill that would not be covered entirely by his insurance, I also had to discuss the $5,000 monthly out-of-pocket price tag. This, too, had become part of my informed consent process: risks, benefits, alternatives, and financial toxicity. He declined the treatment in favor of hospice.

As he put it, “I won’t bankrupt my family for a month or two more time. I have to leave them something.”6

People also make decisions to take chemotherapy given chances that I, personally, would have thought to be too against their favor to be worthwhile. These are the gamblers, the folks who “chase the tails” of survival curves, meaning the handful of people in clinical trials who were cured despite the long-shot odds.

In a study that I led when I was still in my training fellowship in Boston, I approached older adults, like David, who were just given a diagnosis of acute leukemia.7 My colleagues and I asked them a series of questions about their quality of life—in other words, how much the leukemia was causing them to feel fatigued, depressed, or worried—and questions about how they made the decision to receive the aggressive, inpatient chemotherapy, or the lower-dose, outpatient option.

We found that physical functioning among patients was more than one-and-a-half standard deviations below the general population (about 30 percent worse) and that 35 percent of patients were depressed—numbers far worse than we would have guessed. The physical functioning scores deteriorated significantly for hospitalized patients after they started the high-dose chemotherapy, but then rebounded as soon as they were discharged back home, and continued to improve over months for those who entered a remission. Among people who chose to receive therapy as an outpatient, where remission rates were less than half of the aggressive inpatient therapy, physical functioning worsened at a slower pace, but never rebounded like it did for those hospitalized. Depression continued to worsen in this group also, reaching a peak of almost 50 percent six weeks after the first survey.

These findings led us to beef up our psychosocial supports for our patients, and to be deliberate in asking questions that touched on their emotions, rather than just their blood counts. Assessing sadness or despondency has become another vital sign.

When we asked people how they made decisions, the results surprised us even more. Almost two-thirds of patients told us that they had not been offered treatment options other than the one they chose—despite conversations taking place that were almost identical to the one I had with David and Betty, in which three options (aggressive chemotherapy, low-dose chemotherapy, or supportive care [no chemotherapy]) were discussed.

Those choosing the aggressive chemotherapy were more likely than those choosing the low-dose outpatient treatment (74 percent versus 47 percent) to say their decision was influenced by their doctor. Yet, when we asked the same patients what they estimated their chance of cure to be, 74 percent reported it to be >50 percent—despite 89 percent of their doctors having communicated the chance of being cured as being <10 percent, as I had to David. This even occurred when the survey questions were administered to the patients and to their doctors just a few minutes after the discussion about risks and benefits of chemotherapy took place.

Why did this happen?

It may be that all the talk about how leukemia arose, how to treat it, the side effects of treatment, the hospital stay, the likelihood the chemotherapy would work, and survival estimates was simply an information overload. In other words, my colleagues and I may be poor communicators in the sense that we don’t convey information in a way that people can process or remember it.

In a study conducted at the Dana-Farber Cancer Institute in Boston and the Fred Hutchinson Cancer Research Center in Seattle, interactions between 40 hematologist/oncologists and more than 230 patients over a four-year period were audio recorded, and the transcripts analyzed.8 The average duration of each interaction was almost 70 minutes.

In one analysis of this study, the most common technique doctors used in communicating with patients was called “broadcasting”: a pattern of lengthy physician monologues on disease mechanisms and history, treatment options, or prognostic information, often lasting for 10 minutes or longer!9 Doctors did not invite interruptions. Some used deferential language (referring to how “some patients” would make a treatment decision, or telling patients “you need to figure out” the right course of action), while others were directive (“I would vote for the first treatment option”). The favored style of communication was one that invited patient participation by using open-ended questions (“What have you been told about treatment for your cancer?”).

People who choose to receive aggressive chemotherapy may choose to remember the best odds, or exaggerate those odds, to bolster the justification for their decision. Or, some may enter a type of adaptive denial to cope with both their diagnosis and the long-shot odds of chemotherapy curing them. A more positive spin to this coping mechanism is to call it optimism, or hope—both of which have been associated with better outcomes among cancer patients. For example, one study showed better early survival among 300 patients undergoing bone marrow transplant, and another study showed improved five-year survival rates for 530 non-pessimistic people with lung cancer.10

If that’s the case, I hope to experience the same adaptive denial if I’m diagnosed with an illness that is potentially terminal.

A separate study in 260 patients undergoing a bone marrow transplant found that those with higher-risk cancers—meaning that their expected survival following the transplant was lower—tended to be much more optimistic about their chances than their doctors. Those with a likely favorable outcome following the transplant tended to have expectations that were more concordant with what their doctors estimated.11

For the study I led during my training, it sometimes took 30 minutes or more to administer the survey questions depending on how many times a patient and I got interrupted. Inevitably, a patient or family member would stop me before I left the hospital room.

“Why is somebody like you asking me all of these questions?” they wanted to know.

I would adjust my white coat, a little bit confused. “What do you mean?”

“You’re a doctor, don’t you have more important things to do?”

More important than trying to understand what it feels like to have leukemia, and how my patients make decisions about their future? I couldn’t imagine what that could be.

I walked over to Joan’s room just as Rachel was leaving.

“How’d it go?” I asked Rachel, who was peeling off a protective paper gown for the second time that day.

“Good. I didn’t feel a thing,” she wisecracked. “Actually, it did go well, but she kept bleeding from the puncture site for a while. I had to hold pressure on it for about 20 minutes, and even then it was still oozing. So I put a pressure dressing on the site and asked Ms. Walker to lie flat for an hour.”

“Do you think it bled more than usual?” I asked. She nodded. “Can you send some coags?”

“Way ahead of you, boss. They’re cooking,” she answered. Rachel was the type of fellow who was so smart that I had to work to find some esoteric fact about our patients I could teach her.

Coags, short for coagulation labs, are a group of tests that measure the ability of the blood to form clots. It’s bad enough that someone has a diagnosis of acute leukemia, which usually causes the platelet count to be low, predisposing that person to bleeding. We already knew that was the situation with Joan. It’s even worse when the blood’s ability to coagulate the sparse numbers of platelets is impaired, a condition called disseminated intravascular coagulopathy, or DIC. DIC can arise as a side effect of certain types of leukemias, or it can be triggered by a serious infection. It can be devastating, as DIC can lead to either life-threatening bleeding, or to the formation of blood clots that could be equally dire.

I knocked on Joan’s open door gently. She was lying flat in bed, now wearing the Diane von Furstenberg duds. There was some blood staining her sheets. Her eyes were shut, and her friend had left the room, probably ushered out by Janey when Rachel performed the bone marrow biopsy. While we loved having friends and family members around frequently to support our patients and help them get through the ordeal of treatment, we have learned from past experiences that once one of us brandishes that absurdly long needle for the biopsy, some people faint. And then we have two patients, instead of one. That situation is one I call an IGBO—I Got Burned Once.

“Hey,” I said softly. She opened her eyes and looked over to me. Rachel followed me in.

“Hey,” she answered, almost reluctantly, as if she didn’t want this next stage of her life to begin yet.

“Okay for me to sit down?” I asked, gesturing to her bed. She nodded, and I introduced myself. “You know why you’re here?” She nodded again.

“I sure would have liked to be meeting you in the outpatient clinic in Wooster,” I offered. She grimaced. “I hear you’re a surgical nurse. You have a really good group there. Your patients are lucky to have you.”

“Yeah, they’re the best,” she agreed.

“We’re pretty concerned that you have leukemia,” I said. “What do you know about it?”

“Only that anyone I’ve taken care of with leukemia in the ICU hasn’t done too well,” She replied. “Especially the bone marrow transplant patients.”

“It’s true, our patients have to be pretty sick to make it to the ICU, and once they get there, many don’t make it out. But some do. And my goal is to keep you out of the ICU as we get rid of this leukemia,” I told her. She was quiet, tearing up a bit.

In many hospitals, there is a bias that cancer patients shouldn’t be admitted to intensive care units, the perception being that they never make it out of them alive. A few years before I treated Joan, we had decided to study this phenomenon to see if it was true. We followed 90 patients with acute leukemia who were admitted to our intensive care unit so we could evaluate how they did.12 Approximately one-third improved enough during their ICU stay to continue receiving aggressive therapy for their leukemia; most of them were eventually discharged from the hospital back home. Those who did not need to be placed on a mechanical ventilator and did not require medicines (called pressors) to raise a low blood pressure had the best outcome of all, with over half surviving the hospitalization. The main take-home message from the study was that people with acute leukemia fared no worse than those with other serious medical conditions who were admitted to the ICUs at the same time. There was no basis for the bias.

Joan’s friend walked into the room with an older woman who came straight over to the bed to give Joan a hug. Joan introduced her to me as her sister Connie. I could see the resemblance, in the eyes and the edges of their mouths. She also introduced her nurse friend Patty.

“Connie’s 15 years older than me,” Joan said. “I was planned, she was the accident.” I laughed as Joan and Connie smiled at what I’m sure was a well-tread joke, repeated over years. Joan asked me to explain what was going on to Connie and her friend, and by association to her too.

I reviewed a lot of the same facts that I had discussed earlier in the day with David and Betty and their children. I shifted some of the outcome estimates given Joan’s younger age, quoting a 70 percent chance of entering a remission, a risk of dying less than 10 percent, and a chance of being alive in five years of approximately one-third. No one took notes, but everyone listened attentively.

“I’m confused,” Connie said. “If Joan has a 70 percent chance of a remission, why does that drop to 30 percent five years from now. Doesn’t remission means she’s cured?”

I reflected back to the study we conducted when I was in my training, and wondered whether the people I surveyed really overestimated their chances of being cured, or were conflating remission estimates with cure. Either way, the onus was on me to do a better job explaining the critical difference.

“We can only detect cancer in the body when you have 10 billion cancer cells. Below that amount, we might not even notice anything abnormal on a CT scan for a solid tumor like lung cancer, or see anything abnormal in blood counts for hematologic cancers like leukemia.”

“So right now, Joan has more than 10 billion leukemia cells in her body,” Patty commented, her eyes widening at the enormity of the number. A statement, not a question.

I nodded, looking at Joan. “You do. When we give you this first round of chemotherapy, our goal is to reduce that number 1,000-fold or 10,000-fold—by three or four logarithms, down to maybe 10 million cells. If we’re successful, we’ll know it because we’ll perform another bone marrow biopsy on you and we won’t be able to see any of the leukemia cells.”

“Even with 10 million of them still floating around?” Patty asked.

“That’s right,” I answered. “Remission means we can’t see any of the leukemia using a microscope to view a section of the bone marrow, with the blood counts mostly recovered back to normal. Remission is a wonderful thing. It’s the first step toward being cured. But it doesn’t mean the leukemia’s gone.”

“So you have to give more chemo after that, to get rid of what’s left over,” Joan said.

I nodded again. “Yup. That’s what we call post-remission therapy. It’s mainly done in the outpatient clinic. Every time we give another cycle of chemo, we hopefully reduce the number of leukemia cells another 100- to 1,000-fold. So, from 10 million cells to 100,000, and then from 100,000 to 1,000, and so on. Eventually, there is such a low level of leukemia remaining that, hopefully, your immune system can gobble up the rest.”

“And then she’s cured,” Patty said. I agreed. “Even at a genetic level?”

I hesitated. “You’ve been doing some reading?” I asked Patty.

She nodded. “What I could on the drive up here.”

She seemed like a great friend, and a super advocate for Joan. I hoped I was lucky enough to have someone like Patty with me if I ever had a serious illness.

“Leukemia starts when something goes wrong in the genetic machinery of the bone marrow cells—the blueprints for the cell.” I clarified that most of the time these weren’t genes that were passed down to children. “When we talk about remission, we said that we couldn’t see any leukemia cells as hard as we look. Sometimes, though, we can still detect the abnormal genes. This is a condition we call minimal residual disease with a morphologic remission—we can’t see the leukemia cells, but we know they’re still there because the bad genes are lurking. We can sometimes use that information to our advantage—it means there’s a greater likelihood the leukemia will return despite the traditional remission, and we might intensify the therapy we use in the future, even recommending a bone marrow transplant. So we’ll look for any of these genetic abnormalities to see if we can follow their levels over time.”

“Can you treat any of the genetic abnormalities?” Patty asked.

“We can,” I answered. “There are a couple that have been discovered in the past few years that are associated with AML. One, called FLT3, can be targeted with a drug that was just approved in 2017. People who received the drug, along with chemotherapy, lived longer than those who were just treated with the chemo. Another, called IDH2, can be treated with a pill.”

Patty and Joan were rapt with attention. Connie stared at Joan, her eyes unfocused, probably still shell-shocked that her younger sister had a life-threatening diagnosis.

I hesitated before I continued, wanting them to absorb what I had just said but not wanting to raise their hopes prematurely with what I had to say next. I gestured to Rachel.

“Rachel tells me that you had some bleeding after she performed the biopsy.”

Joan glanced quickly at Rachel, then back to address me. “I guess so. The young doctor did a good job with the needle, but could use a little work on her pressure dressings,” Joan joked.

“Hey, hey, they haven’t taught us that in fellowship yet!” Rachel answered, joining the repartee. “The bleeding stopped, didn’t it?”

“Doctor, eventually all bleeding stops,” Joan quipped. She was a riot.

“Great point!” I laughed. “But in all seriousness, while the bleeding could have occurred with your low platelet count, it also may mean you have some DIC.”

“That’s not good,” Joan answered, alarm now replacing her previous, mischievous look. “When my patients develop DIC, they almost never make it out of the hospital alive.”

“Well, maybe. But paradoxically it may actually be an encouraging sign. DIC can occur with any type of leukemia, but it occurs more frequently with one subtype, acute promyelocytic leukemia, or APL, which has a really good prognosis. We were just talking about the genetics of leukemia. This one is associated with abnormalities of chromosomes 15 and 17.” A translocation, like with BCR-ABL in Ms. Badway’s chronic myeloid leukemia. “We’re sending tests both to see if you have DIC, and to check if you have this type of leukemia. I should know more later today about the DIC, and by tomorrow about the leukemia.”

“We’ll keep our fingers crossed,” Patty responded.

“Yes,” Connie added, looking at Rachel and me. “Fingers and toes.”

If you’re playing the parlor game “What kind of leukemia would I want to get?” the answer of course, is “none.” But if forced to claim one, my answer would be CML. If the follow-up question asks which kind of acute leukemia would I want to get, the answer would be acute promyelocytic leukemia or APL.

And it goes without saying, that if these are the types of parlor games you’re playing, you need to get out more often.

APL used to be a death sentence. It was first described in 1957 by a Norwegian hematologist, L. K. Hillestad, who wrote that its “most outstanding feature was its very rapidly downhill course of few weeks’ duration, a white blood cell dominated by promyelocytes and severe bleeding.”13 The severe bleeding was brought about by the DIC we suspected in Joan. Promyelocytes, like blasts, are immature white blood cells doomed to an eternal childhood by the translocation of chromosomes 15 and 17, which blocks the cells from becoming a functional immune system. Janet Rowley at the University of Chicago—the same Janet Rowley who discovered the BCR-ABL translocation in CML—identified this genetic basis for the leukemia.14 Her work on the genetics of leukemia earned her a Lasker Award in 1998 and a Presidential Medal of Freedom award in 2009.

In APL, the promyelocytes have a peculiar appearance. Their interiors are filled with azure-colored granules, which will sometimes stick together to form rods. These are called “Auer” rods, after the physiologist John Auer, who described them in 1906 in a 21-year-old patient suffering from nosebleeds, although Thomas McCrae, a physician at Johns Hopkins, had described them also, a year earlier. Auer rods resemble bunches of sticks—known as faggots—a linchpin in making the diagnosis.15

It wasn’t until the early 1970s that any chemotherapy was reported to successfully mitigate this dismal outcome. That chemotherapy was daunorubicin (the same drug we discussed with the Sweeneys), which improved remission rates in 80 patients with APL treated at Hôpital Saint-Louis, in Paris, from 13 percent to 57 percent.16

Meanwhile, in the lab, a couple of groups of scientists were discovering that leukemia cells could be triggered to undergo maturation (toward becoming functional white blood cells) with certain agents, including retinoic acid.

The next major breakthrough in treating APL came in the mid to late 1980s. Zhen-Yi Wang, a doctor in China, gave a pill called all-trans retinoic acid (ATRA) to a five-year-old girl with APL whose disease did not go into remission after treatment with daunorubicin.17

This was nothing more than a vitamin A derivative. She went from a condition that, in Wang’s words, was “hopeless” to a remission, and eventually was cured. He then reported the results of his experience treating 24 patients with APL (some of whom had disease recurrence after previously being treated with chemotherapy) at the Rui-Jin Hospital in Shanghai. Remarkably, 23 of his patients achieved a remission—with a vitamin!

And these patients didn’t experience the precipitous, life-threatening drop in their blood counts that I had described to the Sweeneys, the necessary evil of standard chemotherapy. Wang’s findings upended the dogma of needing to treat all leukemias with toxic chemotherapy.

As with Brian Druker’s research on treatments for CML, though, there were doubters. For starters, the clinical report of the vitamin’s efficacy preceded the knowledge about the genetic basis for APL, and how that translocation caused the promyelocytes to freeze at their immature development stage. This finding would subsequently be elucidated in the early 1990s in increments: first with cloning of the translocation of chromosomes 15 and 17 and identification of the relevant genes (subsequently named the retinoic acid receptor alpha [RARA] and promyelocytic leukemia [PML] genes); next with experiments in cells that mimicked APL and with recapitulation of APL in mice, similar to what George Daley and David Baltimore had done with CML; and finally with research that determined how the translocation caused the promyelocytes to stop maturing.

Another more sinister reason why the report from Wang didn’t change medical practice overnight was because some doctors in Western countries simply didn’t believe him. Many trained in Western medicine have a longstanding mistrust of Eastern medical practices. Acupuncture for back pain? Herbal remedies for colds? A vitamin that can cure leukemia? Yeah, right!

Some of the explanation for the use of ATRA to treat APL was steeped in Confucian philosophy and its belief in the rehabilitation of criminals. Wang and a former star PhD student of his, Zhu Chen, quote a relevant passage from the Analects:

If you use laws to direct the people, and punishments to control them, they will merely try to evade the laws, and will have no sense of shame. But if by virtue you guide them, and by the rites you control them, there will be a sense of shame and of right.18

The disease control model in China was influenced by this ancient philosophy about ways to control society. ATRA caused the criminal bone marrow elements (corrupt promyelocytes) to become stand-up citizens (mature white blood cells). Western doctors, in particular, were more likely to take college courses in biochemistry than near-Eastern philosophy, and probably did not buy in to the theory.

So, unfortunately, the delay in the uptake of ATRA resulted from a pervasive mistrust among Western scientists about the validity of research coming out of China, that continues to this day.

“They lie,” I have heard colleagues say, referring to Chinese investigators.

“I just don’t believe the results.” I have seen this statement among comments from people reviewing Chinese research submissions to Western medical journals—submissions that were subsequently rejected.

Was this suspicion due to language barriers? A cultural divide? Racism? A recognition that Chinese scientists may be under more pressure to show success at any cost? Probably a bit of all four.

Wang and Chen started collaborating with doctors at Hôpital Saint-Louis around the same time (1988) as their publication. When similar results were reported in French patients in 1990, the mighty little vitamin could no longer be ignored.19 It ushered in a decade of clinical trials that incorporated ATRA into various chemotherapy regimens. Chemotherapy wasn’t abandoned, because investigators realized that the remission attained with the ATRA pills alone usually lasted just a few months. But when chemotherapy was combined with ATRA, the treatment approaches packed a one-two punch that led to remissions in about 90 percent of patients, and a cure rate that approached 80 percent.

In fact, unlike with other acute leukemias, for which chemotherapy can either lead to remission, death, or can be ineffective—with a person neither achieving remission nor dying—in APL, treatment regimens incorporating ATRA have a binary outcome: remission or death. And most people who die do so because of bleeding complications, almost uniformly as a consequence of DIC.

The junior resident, John, came up to me and Rachel as we returned to the hallway outside Joan’s room. He looked even more disheveled than he had that morning.

“You need to get home buddy, I worry about you,” I said to him.

“What, and miss out on all the learning I could be doing here?” He smiled at me, wanly. It sounded like the sort of thing I would say when I was a resident.

“I’m almost done, just tying up some loose ends. The Sweeneys want to speak with you.”

“Has he decided about chemotherapy?” I asked.

“I think so,” John answered. “There was a pretty heated conversation going on in there earlier. It’s calmed down.”

I walked over to David’s room, with Rachel and John trailing, knocked at his door, and entered. Susan was now sitting in the chair Betty had occupied before, while Eric remained leaning against the window seat, his arms still crossed. David lay in his bed, and Betty was nowhere to be seen.

“Hey everyone,” I said. David lifted his hand in greeting, and Susan said “Hi” in a whisper. Her eyes were red from crying. Eric nodded at me. “Have you made a decision about your treatment, or do you have any more questions you’d like to ask?”

“Doc, I’d like to get that high-test chemo you give in the hospital. I’m going to give this thing my best shot,” David answered. Susan stared at him intently as he spoke, her eyes unwavering.

“You sure about this?” I asked. “A little while ago you told me you were leaning toward the outpatient chemo. Once we get started with this, it’s hard to back away.”

Eric shifted from one foot to the other, impatiently. Susan looked down.

“I’m sure,” David answered again. “I want to do what’s right for everyone. I can make it through the chemo.”

“We know you can Dad,” Eric echoed.

“Thanks, Daddy,” Susan whispered. She took his hand.

“Okay then. You know I’ll support whatever you decide is right for you.”

“This is what’s right,” he answered.

“I’ll write for the chemo and we’ll get it going in an hour or two,” I said. Eric exhaled, relieved. “Where’s Betty?” I asked. She had been David’s ally when he made his initial decision to take the lower-dose chemotherapy.

“She went down to the cafeteria to get a cup of coffee,” Susan responded.

“I think she needed some alone time,” David added. I could only imagine what an emotional roller coaster this day had been for them all.

Back in the hallway, Rachel shook her head, clearly frustrated.

“It’s not right,” she said. “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.”

I nodded my head. “Everything you’re saying is true Rachel. But let me ask you this: Is it wrong to make a decision about your healthcare because it’s in the best interests of your family? For the people you love and who love you?”

David certainly wouldn’t be the only one of my patients who chose a more aggressive path to treat leukemia because that’s what their children or spouse wanted. In the study we conducted during my training fellowship, we also asked people with leukemia what influenced the treatment decision they eventually made. Most (97 percent) reported that quality of life was more important to them than length of life. A majority (61 percent) said that their doctor influenced their treatment decision, and 30 percent went so far as to say that their doctor (and not they, themselves) made the decision about their medical care. But a group of patients (21 percent) told us that their family influenced their treatment choice. Interestingly, 11 percent admitted that they had seen a friend or family member receive chemotherapy and didn’t want any part of it based on what they observed.

I’ve also cared for people who decided on less aggressive paths because of family considerations. One woman in her late 60s declined inpatient chemotherapy because she had to return home to look after her mother, who was in her 90s.

“She has dementia. She depends on me,” my patient told me.

“Do you have any siblings who can help out?” She shook her head. “What about finding a place for her in a long-term care facility?”

She shook her head more vigorously. “No way. I promised her I would take care of her, that I’d never let that happen. And that’s what I’m going to do.”

A lot of my patients are older, and live their lives bouncing from one medical catastrophe to another, organizing their weeks around their own or their partner’s doctors’ appointments.20 Another patient, a man in his 70s with leukemia, was married to a woman who developed colon cancer at the same time. He delayed his treatment so he could care for her while she was getting chemotherapy, and then she delayed a subsequent round of her therapy so she could care for him.

People make sacrifices for each other when it comes to health, just as they do for families and careers. Each of these decisions was the right one to make at that time, for that person.

“I would choose what’s best for my health if I had leukemia.” Rachel said.

“Fair enough,” I responded. “You and I are at different stages of life than Mr. Sweeney, Ms. Badway, or Ms. Walker. Our job is to help them make their own decisions.”

The leukemia pharmacist, whose name was Caitlin, walked over to us. Ms. Badway was following her down the hallway.

“Could you sign the order for Ms. Badway’s Gleevec?” she asked me.

“You decided to take the pill?” I asked Ms. Badway, as she approached us.

She nodded. “I gotta do whatever I can to fight this leukemia. My health has to come first. I’ll feel terrible if the baby gets birth defects, but I’m not going to do him or any of the other kids any favors if I’m not around.”

“I understand,” I said to her. “I think it’s a good decision. Let’s get you the pills and you can bust outta here. I’d like to see you in a couple of days in my clinic, and we’ll need OB to follow you weekly also.”

“You really think it’s a good decision?” she asked, stroking her belly gently.

“I wouldn’t give you any options that I wouldn’t support 100 percent.” I answered. “It’s a great decision. It’s what’s best for you.”