7 A Life Extinguished, a Life Awakened

end of his life his life began

to wake in me.

—Sharon Olds, “His Stillness,” 1992

How strange, hearing the disconsolate cry of a newborn in a cancer center.

These monotonous white hallways—punctuated by honey-colored doors, sterile foaming cans, and subtle plastic “flags” by the door frames that indicate what room would be attended to by which doctor—conveyed professionalism, competence, cleanliness. The gray carpeting acted like a damper when important conversations occurring on the other side of the doors spilled out to the corridor: hushed tones, bursts of laughter, muffled relief, muted despair . . . but almost never the full-throated release of an infant demanding to be fed, NOW!

This kid had a set of lungs on him. Not wanting to add to the chaos, I waited until it sounded like Joseph Jr’s needs were being met before I knocked on Sarah Badway’s door and entered the room.

Sarah was sitting in the chair near the desk wearing black yoga pants and a purple top. She was cradling the baby, who was wrapped like a burrito in a white blanket with tiny gray elephants on it. A shock of black hair peeked out from a blue hat. He sucked away from a bottle of formula, all business, eyes half closed.

“It’s about time you dropped by to meet Joey,” Sarah scolded me. “Didn’t you hear him call for you?”

“Honestly, I think habitants of remote regions of the Amazon basin heard him call for me.” Sarah laughed. Her eyes looked tired. “He’s a really handsome guy.”

“Yeah, I think I’ll keep him,” she said, fussing with his hair.

“He sleeping okay?” I asked.

“Not bad. Goes to bed at 11 at night, wakes up at 4 for another bottle, then again at 7. I’ll tell you, he sleeps better than the others did. I think it’s the formula.”

I had advised Sarah to avoid breastfeeding while taking the imatinib for her CML, as studies have shown that, in women taking the drug, amounts of it can be found in breast milk.1 We didn’t need Joey to receive the chemotherapy unnecessarily. His blood counts, checked by his pediatrician, were normal—there had been no vertical transmission of Sarah’s leukemia.

“And how are you doing?”

“Better,” she said, looking up from the baby to me. “I’m better. I won’t lie to you, there are times when I’m dealing with him or with the others and I forget to take the medicine, but I remember it later on. I don’t think I’ve missed a day,” she reassured me.

“I could tell. Your blood counts look good. And the Philadelphia chromosome is almost gone.”

We continue to assess the BCR-ABL genetic translocation of the Philadelphia chromosome every three months for the first couple of years of therapy, ensuring that the genetic abnormality exists in fewer and fewer cells over time. It’s measured with a lab test called polymerase chain reaction, or PCR.

Invented in 1983 by Kary Mullis, PhD, who at the time was working for the Cetus Corporation in Northern California, PCR revolutionized the field of genetics and made possible many of the discoveries of genetic abnormalities found in cancer.2

On a drive through the mountains to a weekend cabin in Mendocino, inspiration hit Mullis for a better way to detect tiny genetic changes housed in the comparatively large chromosomes. He won the Nobel Prize in Chemistry a decade later for his work. Like so many brilliant scientific discoveries, it now seems relatively straightforward: Think of the gene sequence as the “words” that form the “books” of chromosomes. When we know the gene sequence that provides the instructions to make a protein (such as the tyrosine kinase in CML), a complementary gene sequence can be “zippered” to the original. With PCR, that zipper can be copied, and copied, and copied until you have thousands to millions more copies than you started with, allowing the abnormality to be detected, whereas before it may have been hidden within the thousands of genes on a single chromosome—a single misprinted word within a book. Using this approach, PCR can detect even one cell with the BCR-ABL translocation out of 50,000 cells or more.

Luckily, the BCR-ABL translocation can be assessed using a routine blood draw with about the same accuracy as a bone marrow test. At diagnosis, about 90 percent of Sarah’s cells contained the BCR-ABL mutation. Three months later, that number was less than 10 percent of cells containing the mutation. At six months, it was at about 1 percent. Our goal was to get it to less than 0.1 percent.

Why so low? In the study that randomized more than 1,100 people with CML to receive either imatinib or what had been the standard therapy of interferon and cytarabine, in which 95 percent of patients treated with imatinib had normalization of their blood counts, 408 of the 553 people receiving imatinib had chromosomes that went back to normal—no longer showing the Philadelphia chromosome abnormality. Compare that to only 47 of the 553 people who received interferon and cytarabine. And 57 percent of those treated with imatinib who achieved this “chromosome remission” also had a 1,000-fold decrease in the BCR-ABL mutation that could be measured by PCR one year after starting their imatinib—thus reaching a level of less than 0.1 percent of cells with the mutation, our goal for Sarah.3

And none of the people in this 57 percent club had CML that worsened in the subsequent year of follow-up.

Sarah was on the right track with the timing of her falling BCR-ABL percentages, too. Another study of almost 300 people with CML treated with imatinib showed that those whose BCR-ABL levels were less than 10 percent at the three-month time point, like Sarah, were significantly more likely to be alive eight years later—with a 93 percent survival rate, compared to only 57 percent for those whose levels were greater than 10 percent.4

Imatinib is called a “tyrosine kinase inhibitor”—it blocks the abnormal CML protein (tyrosine kinase) produced by the Philadelphia chromosome that is stuck in an “on” position, which causes the cells to grow uncontrollably.

When Sarah was first diagnosed with CML, Rachel had asked about other more potent tyrosine kinase inhibitors—the “sons” and “daughters” of imatinib, called dasatinib and nilotinib. Two studies published in 2010 that enrolled almost 1,400 patients showed that the new drugs enabled significantly more CML patients—over 60 percent more—to achieve that magical BCR-ABL level of less than 0.1 percent. And they got to this milestone faster.5

Newer generation tyrosine kinase inhibitors—the grandchildren and great-grandchildren of imatinib—bosutinib and ponatanib—seem to work even better, albeit with different side effects to worry about.

So now that Sarah was no longer pregnant, the question remained as to whether I should recommend changing her treatment to one of these newer drugs. Well, with five-year follow-up of the “sons” and “daughters” trials, published in 2016, survival was similar for those treated with imatinib or with a son or daughter drug.6 Since she was tolerating the medicine, taking it regularly, and achieving her milestones, why mess with success?

We had discussed whether to switch drugs just prior to Joey’s birth. But despite her early missteps with taking the imatinib, Sarah had become almost protective of the drug, and didn’t want to abandon it. She set phone alarms to remember to take her pill daily, and even left her amber pill bottle out on a shelf by her bathroom sink as a visual cue. She was proud of her new zealotry around medication compliance. She’d been bragging about it to me a few months earlier, around the time she was about to give birth to Joey.

“Go ahead, ask your question,” she had challenged me when I saw her.

“Have you had any alcoholic beverages recently?” I asked.

Sarah looked at me like I was four kinds of idiot and gestured to her shirt. It was black with white lettering that read “SOBER . . . UNTIL MARCH.” I laughed, though not without some hesitation given her past wild days. My favorite of her pregnancy shirts showed a computer’s spinning wheel on her belly with the message “LOADING . . .” underneath.

“How have you been doing with taking your pills?” I obliged.

“100 percent perfect!” She was almost shouting. “No misses, all net!”

I congratulated her effusively, and she beamed. “When’s the big day?”

“I scheduled the C-section for next Thursday,” Sarah said. “Hey, and about that. A couple of my girlfriends asked if I was going to save the cord blood. Waddaya think?”

“Why are you considering it?” I asked.

She shrugged her shoulders a bit. “I dunno. Maybe for him, in case he gets cancer. Maybe for me if I ever need it.”

Banking cord blood in case a bone marrow transplant is needed in the future is appealing on so many levels. The umbilical cord attaching the developing fetus to its mother’s placenta is rich in those juicy bone marrow stem cells that are so effective at making the blood components. Coming from an infant at the time of birth, they should be uncorrupted by cancer. Cord blood is also easy to collect: At the time of delivery, after the cord is cut, the remaining blood in that cord is milked out into a collection bag. That bag is then kept in a freezer until the time comes, if ever, when it is needed and can be infused as a transplant.

The cost for this, using commercial cord blood banking companies, can be substantial. Upfront charges with what’s called an enrollment fee can range from $1,500 to $3,500. On top of that, a yearly storage fee is assessed, with the total amount for 18 to 20 years of storage cresting $5,000 in some cases.7 Brochures for these companies line Plexiglas display cases in obstetrics offices, with pamphlets exhorting nervous, expectant parents to protect their baby from the medical evils that lie ahead. What better source for a transplant than a child’s own, pure stem cells, harvested at a time years before that child ever developed cancer? Is the cost and effort worth it for the risk that a child may one day develop a cancer and need a future transplant?

There are two ways of answering this question. First, what is the likelihood of a child developing a cancer, and then needing a transplant to treat that cancer?

A study conducted by the Center for International Blood and Marrow Transplant Research attempted to figure this out.8 They first identified the cancers for which transplantation could potentially be needed. For people aged 0 to 19 years (the length of time a cord blood would be kept banked) leukemia was the most common, followed by lymphoma, neuroblastoma, brain tumors, and sarcomas. Cancer in children and adolescents are rare—all told, the incidence rate in the United States for all of these cancers combined was about 12 per 100,000 children per year. It’s horrible if it’s your child who develops cancer, but pediatric cancer is still an uncommon event.

The next conclusion is based on the likelihood that these cancers would not be eradicated by chemotherapy and/or radiation therapy and would require an allogeneic transplant—and the assumption that everyone could identify a sibling or “brother from another mother” transplant and was healthy enough to undergo a transplant. The authors estimated that the incidence rate of transplant for children and adolescents was a little over 2 per 100,000 per year in the United States during their first two decades of life. Analyzed another way, the probability a child will need a transplant by the time he or she reaches age 20 is 0.04 percent.

The lifetime chance of getting struck by lightning is similar, at about 1 in 3,000, or 0.033 percent.9

Would you pay thousands of dollars for a medication right now, in the event that sometime in your life you may be struck by lightning, and that medication may help you survive the lightning strike?

Seems excessive to me.

A second way of determining the value of cord blood banking in case a child develops cancer is to consider whether that cord blood is really as pure as we think.

The most common childhood cancer through age 19 is leukemia, with an annual incidence rate of 4.7 per 100,000 children in the United States.10 Could it be possible that the leukemia was present at some small level even at birth, years before the child was diagnosed with leukemia?

One approach to studying this would be to screen every newborn for leukemia. Given the incidence rate of childhood leukemia, this would mean subjecting over 21,000 babies to a blood test for every case of future leukemia identified. It’s difficult to justify that type of monumental screening effort to answer a research question about the origins of leukemia. A more reasonable approach would be to identify children who have leukemia, and try to determine whether they had it when they were born.

But how to go about obtaining a blood sample from a birth that occurred years earlier? A group of clever scientists from the United Kingdom and Germany thought the answer might be found in Guthrie cards.11

Robert Guthrie was a microbiologist working at the Roswell Park Cancer Institute in Buffalo, New York, in the 1950s when his niece was diagnosed with phenylketonuria (PKU), an inherited deficiency in the enzyme necessary to metabolize the amino acid phenylalanine. If caught early enough, an infant’s diet can be modified so that the effects of the deficiency are minimized. If not, the condition can lead to developmental defects and mental retardation. Guthrie’s niece was not so lucky. This, and having a child of his own with cognitive delays, motivated Guthrie to devote his career to detecting preventable childhood diseases. He developed a test for PKU that could be performed when a drop of blood from a finger prick or heel stick was applied to filter paper on a card. It was successfully piloted in Newark in 1960, and by 1963, 400,000 infants had been tested in 29 states. Testing spread around the country, and across the pond.12

And hospital laboratories kept those Guthrie cards for years after a child was born.

The scientists found three children with acute lymphocytic leukemia (more common in children than AML, whereas the opposite is true in adults) who had the same chromosome mutation associated with their leukemias—a translocation of chromosomes 4 and 11. After obtaining permission from the parents of these children, the scientists then searched laboratory repositories to find the Guthrie cards stored there from when the children were born. They used a PCR-specific lab test for this translocation on the dried blood still remaining on the children’s Guthrie cards, and were able to detect the chromosome abnormality for all three children—from a blood drop obtained months or years before the leukemia was diagnosed. In another, similar study, the same group of scientists was able to detect chromosome evidence of leukemia in 9 of the 12 Guthrie cards obtained from children who diagnosed with leukemia between two and five years later.13

The leukemia was there all along, even prior to birth in these children, waiting years in some cases to rear its ugly head. And if the leukemia was measurable on a genetic level in their blood, it was almost certainly present in their cord blood. Banking cord blood from these children would have preserved those juicy, healthy stem cells, but also probably cells already corrupted by genetic abnormalities that would lead to leukemia—again, if the cells were reinfused into a child as a transplant years later.

Getting back to the question: Is the cost and effort of banking cord blood worth it for the risk that a child may one day develop a cancer and need a future transplant?

I didn’t think so when my three children were born. But I did have their cord blood collected and I donated it to be stored for use through the Be The Match program, in case a complete stranger needed it someday. Maybe my children would be the brothers from another mother, or sister from another mister—me being the mister!

In Sarah’s case, banking cord blood was probably overkill. Given her chances of doing well on imatinib or a similar drug, she was unlikely to ever need a transplant. If she did, her best options would be a sibling or a matched, unrelated donor, not one of her own children. And even if that didn’t work out for her, and she did need a transplant from a child, she has other, older children to choose from who could donate marrow to her at the time she needs it, avoiding all of those cord blood storage enrollment and storage costs.

In any case, there was still the possibility that Joey’s cord blood was contaminated with her leukemia. For all of these reasons, Sarah decided against saving Joey’s cord blood.

As Joey sucked out the dregs of formula, the bottle dropped gently from his lips, and his head lolled back as he fell asleep. Sarah expertly took the bottle away, and with one hand capped it and placed it in the brown diaper bag sitting on the chair beside her. The bag had the same gray elephant design on it as Joey’s blanket.

“Any side effects to the chemo? Nausea? Leg cramps?” I asked softly, trying not to wake the baby.

“All good,” Sarah answered, in her regular voice. “And doc, no need to whisper. If this kid doesn’t learn to nap with chaos, he’ll never get any sleep in my house.”

I laughed as Sarah got up from her chair to put Joey in his car seat, and then sat on the examination table. I checked her from head to toes, asking permission before feeling her neck for lymph nodes. As a medical student, I once examined a women’s neck without asking permission, and she told me it felt as if I were choking her. I later learned that she had been the victim of domestic violence, during which her partner throttled her. I hadn’t appreciated the intimacy of the dance of the physical exam before that. Because of her feedback, I’ve been careful in asking permission to perform exams my entire career.

When I finished, I went to the sink to wash my hands. Sarah gathered her jacket, the diaper bag, and finally the car seat with Joey in it, dead to the world. She swung it gently, rocking him, without even realizing it.

“So, I’m fine for another three months?” she asked. I nodded. “Any chance I can stop taking the chemo?” She smiled at me, acknowledging that the question was a long shot.

It wasn’t as absurd as she might have thought. A couple of studies conducted in Australia and Europe asked just this question: Can imatinib be stopped in people whose BCR-ABL was not detectable using the PCR test?14

In the Australian study, 40 CML patients whose PCR for the BCR-ABL abnormality was negative for two straight years stopped taking their imatinib. With a median follow-up of 3.5 years, 18 of those patients remained in remission and off their drug, without evidence that the CML had returned. All of the 22 patients whose CML returned restarted their imatinib, and all regained their remission. Unfortunately, not all were able to have the same continuous period of negative PCR that first made them eligible for the study.

In a study from France, 100 CML patients whose PCR was negative for two years also stopped their imatinib. With a median 17 months of follow-up, 54 patients had BCR-ABL that returned—a similar percentage as in the Australian study. In a follow-up study conducted at a number of institutions across Europe, more than 750 CML patients with a negative PCR for one year stopped imatinib or other tyrosine kinase inhibitors and were followed for a median of 27 months. About half of these patients (371) had BCR-ABL that returned, and about 300 regained their BCR-ABL negative status after restarting their drug.15

A “glass half full” sort of person might conclude that all those with CML who reach that benchmark of persistent, negative PCR should have a chance at stopping their chemotherapy. A “glass half empty” person might instead think it nuts to stop what is arguably the most effective chemotherapy ever developed, when half of those people had a relapse of their leukemia.

What happened to the people enrolled in the European studies whose leukemia returned? They were restarted on their imatinib, or a son or daughter of imatinib, and most reentered a leukemia-free state. But not all, and it still isn’t known for how long they were able to recapture their remissions.

The point was moot for Sarah, as we could still detect her BCR-ABL.

“Not anytime soon. But there may come a point when we can discuss it. Keep up the good work with taking the medicine,” I said to her, turning from the sink to face her. “Hey, and try to stay out of trouble,” I joked.

“Doc, I got a birthday coming up, and me and my friends are going to rent one of those vans with a driver who can take us around to different bars, to celebrate.” She opened the room’s door and walked out. “But don’t you worry, I won’t forget to take the pill!”

Sarah walked away from me down the carpeted hallway, still swinging Joey’s car seat, before I could say anything. She was returning to family, friends, and her responsibilities outside her doctor’s appointments.

I enter my patients’ lives in medias res, as an interloper conscripted to battle disease, and I do my damnedest to rid them of the malignant golem. But they often come to me with a lifetime of destructive behaviors, and with other medical conditions that preceded the leukemia. And much as I try, I don’t always have the same impact on those other problems.

Later that morning, I checked David’s vital signs scribbled on the paper hanging by his examination room. His blood pressure was “skimming trees” at 98/58, and his heart was clicking away at a rate of 112 beats per minute. He had a low-grade fever at 99 and change.

I knocked on the door and entered. Just as I was about to shut it, I felt a push on it from behind as Rachel squeezed in behind me.

“Sorry!” she whispered as she shut the door behind us.

David sat in a wheelchair by the desk. The room was packed, just as it had been the day we broke the news to the whole Sweeney family that his leukemia had never gone away. He was wearing a Cleveland Indians cap and sweatshirt. So was Betty. Opening day for the team was just a week away, and a bunch of my patients were similarly outfitted, as if through this act of sartorial intimidation they could bully winter into submission and clear the way for spring to finally arrive in Cleveland. The weather in northeast Ohio has a reputation for shrugging its shoulders at these vainglorious attempts; on opening day in April 2007, it dumped enough snow to cancel a game against the Seattle Mariners one pitch before becoming official. In protest one fan ran onto the field, threw himself on the ground, and made a snow angel in right-center field. With typical Cleveland self-effacing humor, the stadium’s PA system played Bing Crosby’s “White Christmas” during a second-inning delay.16

The cap looked two sizes too big for David’s head. He had lost weight, and as his tissue had wasted, the bones around his eyes became more prominent. He still had some of his tan from a recent trip he took with his family, and the darker color belied the degree of anemia he had. Betty looked tired, more resigned, though, than sad. Susan had taken her usual spot on the exam table, and for reasons I’ll never be able to explain regarding the haphazard migration patterns of chairs in the hospital, we were blessed with an additional chair for Eric. So he sat across from his parents and along with Susan greeted us with a smile. As I moved to sit next to David, I saw Rachel mouth to Eric “How are you?” and watched him give her the thumbs-up sign.

David had decided to try the pill that targets the IDH2 mutation found in his leukemia. It took a couple of weeks to clear some insurance hurdles to guarantee the pills would be mostly covered (the drug was priced even higher than other oral chemotherapy for leukemia, at the gasp-inducing cost of $30,000 per month). When he started the treatment, he again experienced nausea like he had in the hospital—not quite as bad, but not good, either. Betty, Susan, and Eric alternately drove him to clinic twice weekly for transfusions. At the same time we could monitor his labs and his symptoms for the differentiation syndrome. Sure enough, three weeks into his treatment, he came to clinic short of breath with a fever and rising white blood cell count.

We admitted him to the hospital and started him on steroids, just as we had for Joan when she had the differentiation syndrome while taking her ATRA. Whether it was feeling sick again, or the toll that making multiple trips into Cleveland had taken on him, or the reminder of what it felt like to be hospitalized so soon after he had returned to living at home, David declared enough was enough.

“I can’t do this anymore,” he had said to us while lying in his hospital bed. Clear plastic tubes wrapped over his ears to supply oxygen to his nose. Only Betty was with him that day. “This is not a life.”

“You can stop anytime you want. You’re the boss,” I had reminded him. “But what if we can get you feeling better with the steroids, and figure out a better regimen to get rid of the nausea?”

He shook his head, and then started to cry. “I can’t, I just can’t.” He covered his face with his hands for a few seconds, quietly sobbing, his shoulders shaking, as Betty moved from her chair to his bed and sat beside him. She hugged him, holding his head and stroking his hair, and soothed him, saying “it’s okay” over and over.

“I’m sorry,” he said to her. “I don’t want to let you and the kids down. I’m sorry.”

She shook her head and started crying herself. “You did everything, honey. You’ve been so brave. It’s okay to stop. We can’t ask anything more of you.”

I sat quietly in the chair by his bed as they comforted each other, watching this husband and wife soothe each other with words and touches in a way that only people who have been together for decades know.

“David?” I said gently, waiting for him to look up. “Let’s stop the pills. It’s the right decision.”

He lifted his hands from his face and nodded. “Thank you,” he answered, barely audible.

Later that day I returned to his room to ask how far he wanted to go in stopping his treatments, and how he wanted to live the rest of his life.

“What are my options?” David was sitting up in bed, having regained his composure from earlier in the day, and was back to his pragmatic self.

“We can be as aggressive as you’d like. Some people with leukemia who don’t want the chemo any more still do want to receive blood and platelet transfusions, and even antibiotics if they have an infection. Others don’t want any contact with a clinic or hospital, and choose more of a hospice approach. You’d remain at home, and a nurse would visit you there, and even help provide you with medications to allow you to be comfortable and to live your life as fully as possible.”

“Can’t he have both?” Betty asked. “Transfusions and hospice?”

It was a great question. Hospice presents unique challenges in an end-of-life leukemia population, not the least of which centers on leukemia patients needing blood and platelet transfusions to survive. Why would simple blood and platelet transfusions be so hard?

Transfusions of blood products can only be performed in a clinic or hospital, making the logistics of transfusions challenging for a person who is on hospice and homebound.17 Family members of a few of my end-stage leukemia patients have told me it may take them two hours to help my patient wash, dress, and transfer to a car so that person can make it to clinic for a transfusion. At a certain point, it just gets to be too much effort for everyone.

The cost of regular transfusions also exceeds the per diem payment that hospice agencies receive to care for an individual. Many such agencies will not willingly allow a treatment that could put them out of business, harsh as that sounds. A few more enlightened agencies will, though.

Some even argue that blood and platelet transfusions are considered “heroic” therapies, and thus are antithetical to the philosophy of some hospice groups that avoid aggressive treatment of a disease and focus instead on symptom control. Yet a study of more than 100 cancer patients receiving palliative care showed that those receiving red blood cell transfusions had improvement in symptoms of fatigue, breathlessness, weakness, or dizziness.

Whatever the reason, one survey of almost 350 US hematologist/oncologists found that this inability for patients to receive transfusions was a barrier to hospice referral for 62 percent of respondents. From a patient perspective, there are analyses using data from Medicare and from the Surveillance Epidemiology and End Results (SEER) program of the Centers for Disease Control and the National Cancer Institute—one including almost 7,000 patients, the other 21,000: Those with leukemia or myelodysplastic syndrome (the bone marrow condition we suspected of preceding David’s leukemia) who were dependent on blood transfusions were 31 percent less likely to use hospice.18 For those who did use hospice, they spent a significantly shorter amount of time in hospice (at a median of 6 versus 11 days), and a separate analysis showed that they were significantly more likely to die in the hospital, rather than at home.

“I still want the transfusions,” David said. “I can’t go long without getting blood and platelets, right?” He had been receiving a transfusion of each every week or two. I nodded in response. “Well, then let’s just continue those and hold off on hospice for now.”

“How soon can he get out of the hospital?” Betty asked, having returned to her chair.

“A day or two, let’s make sure this differentiation syndrome has gotten better and that David doesn’t have an infection,” I answered.

“Good. We decided that we want to go on a trip down to Florida, to the Gulf Coast. We go down there every year around this time. Is that possible?” David asked.

I nodded again. “We’ll have to work it around your transfusions, and I’d like to find a hospital near where you’re heading, so that if you get sick you’ll know where to go. But if that’s what’s important to you, we’ll make it happen.”

David seemed satisfied, and lay back on his pillows. “I want to spend the week with my family, sitting in a chair staring at the ocean, just thinking about where we all came from.”

Too many leukemia patients at the end of life spend their time in clinic or in the hospital. One study of 330 people with AML diagnosed between 2005 and 2011 found that, once diagnosed with leukemia, patients were hospitalized four times on average. Those who died spent over 28 percent of their lives from the moment of diagnosis in the hospital and almost 14 percent in clinic. Within 30 days of death, 85 percent were hospitalized, 45 percent had received some type of chemotherapy, and 61 percent died in the hospital.19

In addition to the operational and economic hurdles in engaging hospice, and the reluctance of doctors and nurses to stop therapy once it’s been started, a more subtle explanation for high hospitalization and treatment rates at the end of a leukemia patient’s life is that people’s goals change, sometimes suddenly. It often takes a sentinel event like a side effect to chemotherapy, or yet another hospitalization, for a person to realize, “I can’t do this anymore.” When the treatment brakes are applied for a fast-growing cancer like leukemia, it may not take long, even less than 30 days, for a person to die from the disease.

Two months later, David sat in clinic wearing his Indians gear. Fortunately, he hadn’t gotten any infections since his hospitalization, and the frequency with which he needed transfusions had been pretty stable, until recently. He now needed blood or platelets two or three times each week.

Rachel and I saw him often, sometimes alone with Betty, sometimes with her and Susan, and occasionally with Eric. Rachel got to know Eric better, and even apologized for how she had reacted to him. Water under the bridge, now.

When David made his decision about not receiving any more chemotherapy, Susan and Eric supported him. Maybe it took tincture of time, maybe it was seeing what he had endured at the hands of his disease and the chemotherapy. Maybe it took staring at the Gulf of Mexico, thinking about where we all came from.

“It’s getting to be a lot, coming in here all the time,” David said, his voice not as resonant as it once was. “On me and on all of them.”

Susan rolled her eyes. “Daddy, it’s no trouble for us at all. It’s nice we get some time alone with you.”

David smiled at how she soft-pedaled the disruption to her life, to all of their lives. They had raised her well. He continued. “I’m thinking it might be time we get that hospice involved and stop these transfusions.”

“We’ve worn out our welcome, have we?” I asked.

He smiled again, wanly. “Besides, I don’t want to miss opening day next week because I’m sitting in one of your infusion chairs.”

“That would be my choice, too,” I told him.

Could David make it long enough to see opening day? I’ve long been convinced that, at least to some extent, and within the boundaries imposed by the aggressiveness of their cancers, my patients die only when they’re good and ready to. For many, that time occurs after they have achieved a specific goal. Perhaps it’s the birth of a grandchild, or that grandchild’s college graduation. Maybe it’s seeing the long-lost sibling a patient has been feuding with for years. Parents always wait to say goodbye to their children: I have seen patients, even those moribund and comatose, linger for days until a daughter or son from overseas arrives.

One patient, a man in his late 60s who had multiple cancers, told me his goal was to walk his granddaughter down the aisle at her wedding.20 He and his wife had raised her while their daughter, who had gotten pregnant in her teens and then became addicted to drugs, struggled to get her life back in order.

After surviving colon cancer years earlier, he developed lung cancer. Prior to treating that cancer, the lung cancer specialist referred him to me when he noticed the patient had abnormal blood counts. A bone marrow biopsy revealed both acute leukemia and another bone marrow cancer, multiple myeloma.

Three cancers at the same time, four in total, but you’d never know it from his attitude.

Determined, positive, and uncompromising: none of these cancers would keep him from that wedding. The chemotherapy knocked his blood counts down, but didn’t do much to kill the leukemia. The lung cancer spread to his brain, leaving him partially paralyzed. We treated that well enough, with steroids, so he could walk again.

“You should have heard the gasp from everyone in the church when he came through those doors with our granddaughter,” his wife told me. “No one thought he would be there.”

But I did.

I saw him one last time after the wedding. He wore a sweatshirt with a photo transfer of him and his granddaughter walking down the aisle. The caption read “Mission Accomplished.”

This kind of “will-to-live-until” phenomenon has even been studied. Investigators from Ohio State University explored whether people with cancer die soon after they achieve a milestone, which for the study was defined as a birthday, Thanksgiving, or Christmas.21 They examined death certificates from over 300,000 people who died with cancer in Ohio during an 11-year period, from 1989 to 2000. It was a negative study, though; people with cancer were no more likely to die after these events than before.

The authors concluded: “Analysis of thousands of cancer deaths shows no pattern to support the concept that ‘death takes a holiday.’ We find no evidence that cancer patients are able to postpone their death to survive Christmas, Thanksgiving, or their own birthdays.”

But I’ve always felt the study focused on the wrong “milestone.” I haven’t looked forward to a birthday for decades, and when I did it was only at seminal transitions: from 15 to 16, when I could finally drive my mom’s Toyota Tercel, and 20 to 21, when I could hold my head high as I walked into a bar in my home state of Rhode Island using my real driver’s license, not the one claiming I was from Lumberton, New Jersey. Holidays are a mixed blessing for even the most hale and hearty of us, particularly if they involve travel with young children hopped up on sugar, and an unwelcome break from routine.

The other people I’ve witnessed who seem to have some say in when a dramatic, health-related life event will occur are pregnant women. I can’t count the number of times during my wife’s pregnancies when someone commented that she would go into labor only after she’d “finished nesting”—that is, preparing for the birth and completing other tasks she needed to accomplish before going on maternity leave. Put these two together—a person on the cusp of dying, and a pregnant woman at term—and we have the makings of a serious stalemate.

A few years back, I cared for a woman who had end-stage cancer. She had slipped into a coma, but before doing so declared that she wanted to live long enough to see the birth of her first grandchild. Her 40-week-pregnant daughter, who was by her side daily in the hospital, declared that she would not leave her mother to go into labor, for fear that she wouldn’t be present when her mother took her last breath.

We witnessed this standoff for almost two weeks, until the daughter’s obstetrician felt it was too dangerous to let the pregnancy continue any longer. The daughter left, reluctantly, to have a Caesarian section, returned hours later with the baby in her arms, and her mother died later that night.

Coincidence?

I think I would live long enough for one of those impossible-to-measure-in-a-study family-life events.

Some people have such tight relationships with sports teams that those teams figure prominently in death plans. One famous Cleveland fan, Scott Entsminger, made a request in his Columbus Dispatch obituary that six members of the Browns football team serve as his pallbearers “so the Browns can let him down one last time.”22 It wasn’t a complete surprise, then, for David, with his family all around him, to focus his death plans on the Cleveland Indians.

“Goodbye, and good luck, David. It’s been really nice getting to know you.” As I rose from the chair, I held out my hand to shake David’s. He took hold of it, and my gaze, for a few final seconds. We both knew this would be the last time we would see each other. I hugged Betty and Susan, and Rachel hugged Eric goodbye.

He made it to see the Indians opener on TV, and died the following day. The Tribe even managed to win the game, in 10 innings.

“Are you ready for your new birthday, Joan?” asked Tina, her nurse.

Joan was lying in a bed in the bone marrow transplant unit, around the bend from where she had just spent another four weeks on the leukemia service. Fortunately, that round of chemotherapy had done the trick and knocked her back into a remission. Also fortunately, her transplant team had been able to identify five potential matches through the Be The Match database. They chose the youngest, a 32-year-old man who was living in Western Europe. A study of almost 1,300 acute leukemia patients in Europe undergoing transplant over a 10-year period found that patients over the age of 40 were significantly affected by increasing donor age, with a higher likelihood the leukemia would return and worsen overall survival if the donor were older than 40.23 The European man happened to be available and willing to donate his marrow; eight weeks after her discharge from the leukemia service, Joan was ready to receive it with open arms.

Well, with an open marrow. Joan had been in the transplant unit for about a week receiving a “preparative regimen” of chemotherapy to wipe out any remaining leukemia cells and any normal stem cells populating her marrow. As a result, her platelets and white and red blood cells were in the toilet. Her donor’s marrow would now rescue this wasteland by repopulating it, which would take three to four weeks. We would know this had happened because her blood counts would recover—with blood cells manufactured by her donor’s marrow, hopefully.

“I’ve decided to name him Lars,” Joan declared.

“Your donor?” her best friend Patty asked. She was sitting in a chair by Joan’s bed, as was Connie.

Joan nodded. “I’ve also decided he’s six-foot-four, with piercing blue eyes and a beautiful head of blond hair.” She ran her hand distractedly over the peach fuzz of brown hair on her own head. “He’s an independently wealthy businessman who likes to sail, travel to exotic places like Canton, Ohio, and cater to my every need.”

“Another independently wealthy boyfriend? Jeez, Joan, you collect them like candy!” Patty teased her.

“Can you actually find out who he is?” Connie asked.

“Only after a year. I have to give permission, and he has to give permission, and then I’m allowed to contact him.”

“Joanie, you sure you have the energy for a guy 16 years younger than you?” Patty asked.

“You’re about to find out!” Tina said, as she lifted the bag of cells and hung it on Joan’s IV pole. It looked smaller than Joan expected, for all of the effort it took to get those precious cells. Slightly bigger than a bag of blood, and a similar shade of red.

“You sure those are the right ones?” Joan asked Tina, only half joking.

“I checked them three times, together with Janey. So did the cell-processing lab. These are your cells.”

“I looked at ’em also Joanie, you’re good to go.” Patty added.

Joan sighed. “Okay, okay, I trust you. Let ’er rip!”

Tina attached the tubing between the bag of cells and the long-term Hickman catheter inserted into one of the major veins in Joan’s chest. The red liquid started flowing.24

“When should I start sucking on the mints?” Joan asked. A bowl of wintergreen Lifesavers, individually wrapped in clear plastic, sat on her bedside table.

“Yeah, what’s up with those?” Patty asked.

“Now is good,” Tina told Joan. “The bone marrow was frozen to transport it overseas. It was placed in a preservative called DMSO that can cause a strong taste of garlic or creamed corn in your mouth. The mints help make that more tolerable.”

“My skin may even smell like garlic,” Joan added.

“You better hope Lars isn’t a vampire, Joanie!” Patty laughed.

They were quiet for a little while, watching the cells in the bag slowly deplete as they flowed into Joan.

“Oooh, I’m getting the taste now,” Joan said, reaching for another mint. She looked up at what remained in the bag of cells as she unwrapped one of the Lifesavers and popped it into her mouth. “It’s kind of anticlimactic after all this, isn’t it?”

“I’m good with that,” Tina said. “We don’t like excitement around here.”

They were quiet again, watching the bag. Then, a knock on the open door and I walked in. I had been watching and listening to them from the nurse’s station, the ebb and flow of their conversation, the quiet looks they gave each other. Hope, support, anticipation, worry, hope, support. The cycle of cancer emotions.

“Happy birthday, Joan,” I said, suspecting Tina had already wished her the same.

“I’m not sure I’m ready to switch over from being a Virgo to . . . what sign is it now? Aries?” Joan asked.

“Pisces,” Connie said. “You’re a Pisces now.”

“I don’t even like fish,” Joan said miserably. We all laughed. “And what blood type will I be?”

“You should just be grateful Lars is such a good match,” Patty said. She turned to me and clarified, “Joan named her donor.”

“When Lars’s bone marrow takes over, you’ll go from being O positive to B positive,” Tina reminded her.

“Be positive,” Joan repeated. “I’ll do my best.”

“It doesn’t take over immediately?” Patty asked.

“Nope. For a while, the two bone marrows, Joan’s and her donor’s, will coexist,” I explained. “Actually, coexist seems almost too hospitable. A battle will ensue over land rights to the precious space in Joan’s bones. The majority of the time, the healthy donor bone marrow wins, which usually takes a few weeks. But until then, we’ll be able to see both sets of bone marrow cells hard at work—what we call a chimeric bone marrow.”

“Chimeric?” Connie asked.

“From Greek mythology. The Chimera was an animal with a lion’s head, a goat’s body, and a serpent’s tail. For a while, your bone marrow will be part you, and part Lars.”

“Maybe I should have named my donor Aristotle,” Joan mused. She shook her head. “I was sure Connie would be a match. Only 25 percent chance though, huh?”

Connie held a thin smile and looked down at her hands, which were kneaded in a tight ball in her lap. What must be going through her mind at that moment, I couldn’t imagine. Maybe Connie wished she had never participated in the ruse of treating Joan as her sister. Easy to say now, hard when you’re a teenager almost 50 years ago whose parents may have declared it was this or adoption—or getting kicked out of the house. Maybe she should have told Joan the truth before the transplant. But Joan had enough to deal with then, with her leukemia returning, being admitted to the hospital for more chemotherapy, the very real threat of dying. One day, Connie promised herself. When Joan was better.

“Lars is a perfect match. About as good as a sibling.” I had answered quickly, not wanting the awkwardness, of which only Connie and I were aware, to linger for too long.

“You called him my ‘brother from another mother,’” Joan reminded me.

It wasn’t the first time a patient came back at me with one of my quips. Years earlier, I cared for another nurse, this one in her late 20s, with acute lymphocytic leukemia. A fellow I was training, originally from Lebanon, followed her along with me. She had a wicked sense of humor, and our formal medical encounters often degenerated into silliness. At the end of the first year after her diagnosis, when she had completed six months of intensive chemotherapy and was receiving lower-dose chemo—what we called the maintenance phase of her treatment—she handed us each a piece of heavy stock paper.

“What’s this?” I asked her.

“A top 10 list,” she answered simply, waiting for us to review it.

I looked down and read the first few lines.

“He’s sunshine. I’m a spotless mind.”

“I have six months of fellowship left. If I pass.”

“A lot of times in medicine we don’t know why we do things. We just do them.”

“You can’t eat hummingbirds in this country.”

I laughed, suddenly realizing what she had done. At the end of her visits with us, she had recorded some of the more outrageous comments we had made to her. The first occurred shortly after the Kate Winslet and Jim Carrey movie Eternal Sunshine of the Spotless Mind had been released in theaters. The last one derived from a tangent my fellow had once embarked upon of Lebanese delicacies.

At the time they were funny. Reading them in stark black ink with the crisp, white background, though, they were a bit jarring. It taught me how much the words we use in talking about leukemia matter, more than we may realize at the time. She presented us with a list every year, our annual ritual, until her leukemia recurred. She got too sick to record our comments, and the tone of our conversations reflected that, leaving little room for levity. She died by the time her third list would have been created.

“Do siblings who are perfect matches for each other look or act the same?” Patty asked.

I shook my head. “No way. From what I’ve seen, the sibling who’s a match is usually the wild brother with the long beard who lives in the one-room shack in Montana writing his manifesto. The one everyone has always thought was adopted.”

Joan laughed. “That definitely is not Connie.”

Patty nodded as Joan continued smiling at the thought of her straight-and-narrow sister living off the grid.

“Once I break out of this joint, I’m basically under house arrest for a hundred days, right?” Joan asked.

“Yup. You will be so immuno-compromised as these bone marrow cells wage war on each other, and the new marrow starts to make new cells, that we want you to live within an hour of the hospital. That’s in case you spike a fever or develop graft versus host disease, where the new immune system attacks some of your normal tissue.” I explained, more for Patty and Connie’s benefit, because Joan had already learned as much from her transplant team.

“I’ll watch her like a hawk,” Connie said, protectively. She would be Joan’s caregiver during the hundred days.

“All done,” Tina declared, as the final drops of cells flowed through the IV line. You feeling okay?” she asked Joan.

“I still have that garlic taste, but otherwise yeah, fine.” Sometimes people can have an allergic reaction to the infusion, just as they might to a bag of blood or platelets. But for Joan, it had been smooth sailing.

Tina detached the bag and cleaned the medical detritus from the procedure off the bedside table.

“My services are clearly no longer needed here,” I said, getting ready to leave. “Have a quiet day, Joan.”

“You too, doc,” Joan said. Connie mouthed “thank you” to me from across the room. Patty gave the thumbs-up sign.

As I walked out I ran into Rachel in the hallway.

“Did Joan get her cells?” she asked.

“All infused and accounted for.”

“Any reaction?”

I shook my head. Rachel poked her head into the room, waved to Joan, and wished her a happy birthday.

“You ready to hear about this new admission in bed 4?” she asked me.

“Names, not numbers,” I gently reminded Rachel, and took a fresh 3×5 card from the pocket of my white coat. The inexorable cycle of illness continued. “Go for it.”

“Mr. Jensen is a 37-year-old man who was in his usual state of health until about three weeks ago, when he began to experience flu-like symptoms . . .”