An unexpected life: Patient, doctor recount bone marrow transplant progress

Hutch News

An unexpected life

The history of blood stem cell transplant is as personal as it gets for one patient and doctor

March 30, 2015
Dr. Jerry Liebermann in his kitchen at home

Dr. Jerry Liebermann, a 37-year leukemia survivor, cooks at home with his wife, Dr. Linda Harris, in the background.

Photo by Robert Hood / Fred Hutch News Service

As a 22-year-old, Dr. Jerry Liebermann had his whole life ahead of him ― until the day when, suddenly, he didn’t.

After his gums wouldn’t stop bleeding from a routine wisdom tooth extraction, Liebermann was diagnosed with chronic myeloid leukemia and given three years to live. Seeing the distant finish line of his life shift in a moment into sharp, near focus, he grew deeply depressed.

“I just felt like my life had ended and it was all over,” Liebermann said.

But it wasn’t over. Liebermann’s diagnosis was in 1978, that's 37 years ago.

What saved his sanity was help from a psychiatrist, who “taught me to keep on living in my mind no matter what my body was up to,” Liebermann said. What saved his life was hearing about Fred Hutchinson Cancer Research Center, at that time the only cancer center Liebermann could find that was willing to treat him with a transplant of a donor’s bone marrow.

Bone marrow transplant: a milestone in the history of cancer

Fred Hutch’s Dr. E. Donnall Thomas pioneered bone marrow transplantation as a viable, lifesaving therapy for blood diseases like leukemia that were once considered death sentences. A transplant of healthy bone marrow replaces a patient’s faulty blood-forming stem cells with healthy ones. Before bone marrow transplantation, the survival rates for leukemia were near zero; now, some types of leukemia have a 90 percent recovery rate. The technique earned Thomas a Nobel Prize and has now been performed more than a million times around the world.

Bone marrow transplantation is one of the most important milestones in the story of cancer, which filmmakers Ken Burns and Barak Goodman have brought to life in their six-hour documentary, “Cancer,” based on Dr. Siddhartha Mukherjee’s Pulitzer-winning book, “The Emperor of All Maladies: A Biography of Cancer.” The documentary will air on PBS over three days: March 30- 31 and April 1.

Dr. Fred Appelbaum, now deputy director and executive vice president of Fred Hutch, recalled the development of bone marrow transplantation in a recent interview. As a medical student, Appelbaum happened across a paper by Thomas on the new treatment and was fascinated by its promise.

“I thought it was so cool that this was even possible,” he said.

Eight years later, Appelbaum jumped at the opportunity to come work with Thomas. He joined the Hutch the same year Liebermann was diagnosed with CML.

It was hard at the Hutch in the 1970s, Appelbaum said, not just for patients and their families but also for clinicians. Fred Hutch’s clinical staff had to persevere despite seeing about 85 percent of their deathly ill transplant patients die, whether from the transplant itself or from relapse.

But they kept going, he said, because of the successes: patients who went into long-term remission, despite the odds.

“That was incredibly exhilarating. They’d been brought back literally from the jaws of death,” he said.

A transplant that came at just the right time

Liebermann, a Long Island, New York, native, was a first-year medical school student at Stony Brook University at the time he was diagnosed. He remembers going to medical centers up and down the East Coast in search of someone who could help him.

 “They didn’t offer that much,” he said, only treatments with unclear benefits or high relapse rates.

But one of his doctors suggested he call Fred Hutch. Liebermann did and learned that, given his diagnosis and health status at the time, he wasn’t a good candidate for a transplant ― but he was encouraged to call back in a couple of years to check in.

“What’s ironic about the whole thing is that was exactly the right thing to do, because if they’d tried to transplant me originally I wouldn’t have made it,” Liebermann said. “But by waiting until I was sicker and then having the transplant, they had made progress enough to be able to do it, and it worked out.”

In 1981, Liebermann became the first mismatched bone marrow transplant the Hutch ever did for someone with his disease, he said. (“Mismatched” means that Liebermann and his donor ― his father, Frank ― did not share 100 percent of the genetic markers used for matching transplant donors and recipients.) “It was totally experimental,” Liebermann said. As part of his treatment, he was enrolled in several clinical trials aimed at optimizing transplant care. “I was a guinea pig, basically.”

Weighing the odds

Liebermann was lucky that his father could donate to him. On average, only 30 percent of patients find a donor in their families. In the early 1980s, there was not yet a national registry to help transplant patients find a suitable unrelated donor.

The registry ― the National Marrow Donor Program’s Be The Match ― grew out of a transplantation milestone at Fred Hutch: In 1979, Hutch doctors successfully performed the first matched unrelated transplant for leukemia on a girl named Laura Graves, using the marrow of a Hutch laboratory technician. Her family was so inspired by the potential of unrelated transplants that they spearheaded the effort to establish the registry, which was federally funded in 1986 and made its first match in 1987.

“Today there are over 21 million individuals worldwide who have been HLA-typed [human leukocyte antigens used for determining a match] to serve as unrelated donors,” Appelbaum said.

In 1981, Liebermann knew that even though he lucked out by finding a donor, his odds still weren’t great: He was told he had a 50 percent chance of surviving the transplant and, if he did survive, a 50 percent chance of long-term remission. He understood this transplant was his best shot, but he still had a hard time truly wrapping his mind around the idea of recovery in the depths of his illness.

“I remember at some point during my transplant, meeting people coming back at their one-year-after transplant,” he said. “It was so hard to imagine that I could look like that, just a year later.”

Finding love in a traumatic time

Liebermann wasn’t alone in facing his uncertain future. His parents came out with him to Seattle for the transplant, as did his new wife, Dr. Linda Harris, whom he had married only months before.

“If it hadn’t been for Linda, I don’t know if I would have made it through my first transplant,” he said of Harris. “She was always there for me. It was so amazing. She would stay late at night with me when I was lonely and stuff like that.”

The two had a “love at first sight” meeting about a year before Liebermann’s transplant at a Jewish singles event that their mothers forced them to attend.

They were married four months later. “We were kind of on a condensed timeline,” Harris said.

Now married 34 years, they finish each other’s sentences and quibble good-naturedly over details of events from years past. And they joke about how what was supposed to be a months-long marriage has stretched into the decades.

“Linda thought she was getting a really good deal,” Liebermann teases. “She was getting my sweater collection and everything she wanted, and she could get rid of me, and it didn’t work out that way.”

The challenges of transplant

Harris spent every evening with Liebermann in the Fred Hutch transplant ward ― a handful of rooms on the fifth floor of Swedish Hospital in Seattle ― where he stayed for about 40 days, 30 of them post-transplant.

Appelbaum is frank about how difficult transplantation was for patients in 1981, describing how they would endure days of constant nausea from the drugs used to prepare them for the procedure.

“We would give them sedatives so they weren’t constantly throwing up,” he said. “They would be not- quite comatose,” and throw up every time they awoke fully.

Then, there was the risk of infection until their new immune systems took hold, said Appelbaum. “We would be monitoring them with our fingers crossed that they didn’t develop either pneumocystis or CMV [cytomegalovirus] infection.” No antiviral drug to prevent or treat CMV had yet been developed.

In Liebermann’s case, the finger-crossing worked: His father, like most adults, had CMV ― a usually symptomless viral infection that can be deadly for transplant patients with poor immune function.

“Miraculously, I never got CMV,” Liebermann said. “If I had … people died from that. Basically if you got a CMV infection it was a death sentence.”

But then there was the excruciating pain. Liebermann reacted to a drug he was on as part of a trial to prevent graft-vs.-host disease, a dangerous complication of transplant in which the donor cells attack the host’s body.

“I got such inflammation in my hands and feet that the skin started falling off,” he said, recalling that the doctors, never having seen that side effect before, didn’t grasp at first how much pain he was in. Finally, he was put on morphine so he could sleep at night until the effects passed.

Liebermann was allowed to move out of the hospital into an apartment a few blocks away only once he was able to keep food down without throwing it back up, he said. But he continued to experience some nausea after he left the hospital, he remembers. It didn’t help that a drug he was on for a year could only be taken by mouth, dissolved in olive oil, or that the smells of other people’s food wafted through the open air of his apartment building’s courtyard right into his window.  

Since then, Appelbaum said, critical advances in nausea treatment and pain control have made transplantation much more tolerable and less deadly.

“You might think of an antiemetic ― a medicine that keeps you from vomiting ― as trivial,” Appelbaum said. “Nobody likes throwing up, but it’s more than that. The drugs we were using were so nauseating and the vomiting was so severe that people would aspirate some of the vomitus and bring it back into their lungs, which would set them up for pneumonias. Just a thing that seems a minor advance really made a huge difference in the ability of people to tolerate the transplant procedure.”

A succession of new treatments helps life move on

It took Liebermann 11 months to almost completely recover. As the months, and then years, passed, he and Harris became increasingly aware that he seemed to be beating the tall odds against him.

The couple moved to Seattle in 1983 to be closer to Fred Hutch in case Liebermann needed further care. In Seattle, Liebermann ― who by then had finished his M.D. but was too immunocompromised to follow his original plan for a career in medicine ― pursued a degree in bioengineering. Harris, a biophysicist by training, went to work for a biotech company that developed diagnostics.

“Basically, for the next nine years, we worked hard, we played hard, and we decided, ‘It’s almost 10 years, I think it’s safe to start a family,’” he said.

But cancer survivors always live in the shadow of the threat of relapse. In Liebermann’s case, that threat materialized three times in the years after his 1981 transplant: Nine years later, when his daughter Rebekah was just two weeks old, he received a second transplant of his father’s marrow. Then, 18 years after his first transplant, he relapsed again. This time, instead of a transplant, he received a series of treatments, including a failed experimental infusion of genetically engineered donor lymphocytes [white blood cells]. Most recently, he relapsed in 2005. This time, there was a pill: imatinib (Gleevec), approved in 2001 after successful clinical trials at Fred Hutch and other institutions, which blocks a faulty enzyme that causes cancer cells to multiply.

“When I needed a treatment, they had invented the next one,” he said.

The last 34 years have brought numerous challenges ― the double-whammy struggle of having a newborn during a transplant, the horrible immune reactions he experienced during treatment for the second relapse ― but Liebermann says that he loves his life today.

He noted that if transplantation had remained the best treatment available all those years, he never would have been able to survive: His body became too damaged to tolerate any more transplants.

From bone marrow transplantation to the next frontier

Transplantation of blood stem cells continues to be an important therapy for patients with numerous disorders. Thanks to transplant developments at Fred Hutch and elsewhere, patients’ options have expanded beyond bone marrow, including transplants of stem cells circulating in the bloodstream and transplants using the immature stem cells in umbilical cord blood. Plus, new treatment and supportive-care regimens make transplantation an option for both older and younger patients.

Today, Fred Hutch is a world leader in research on immunotherapy for cancer. Immunotherapy is the latest offshoot of the research conducted over the last several decades on transplantation, Appelbaum said, citing in particular a type of immunotherapy that uses a patient’s own cancer-fighting immune cells to attack tumors very specifically.

“This all began as the observation of a graft-vs.-tumor effect in transplantation,” Appelbaum said, referring to the anticancer activity of the transplant recipient’s new immune system. He noted that while much of the immunotherapy research so far has been in blood cancers, there is evidence that these approaches also may be effective in solid tumors, even the deadliest and least-treatable solid cancers, like pancreatic cancer.

“If that happens,” Appelbaum said, “then the legacy of transplantation will be absolutely astounding.” So will transplantation of blood-forming stem cells, so long a cornerstone of treatment for blood cancers and other diseases, be supplanted by immunotherapy in the next several decades?

“We’d sure like that,” Appelbaum said. “I can think of nothing better than being involved with the development of transplantation early in my career to save tons of lives and the development of techniques which do away with transplantation at the end of my career. It would put nice bookends on it.”

On a crisp Seattle evening, Liebermann sat next to his wife at a restaurant overlooking Lake Union as the sun went down and looked back on the full life he wasn’t supposed to have.

“I can’t get over it,” said the 59-year-old who once expected to die before age 30. “I can’t believe that I’m still around. I think of my story, and I’m just glad I’m waking up on the right side of the grass.”

Fred Hutch News Service writer Mary Engel contributed reporting for this story.

Susan Keown is a staff writer at Fred Hutchinson Cancer Research Center. Before joining Fred Hutch in 2014, Susan wrote about health and research topics for a variety of research institutions, including the National Institutes of Health and the Centers for Disease Control and Prevention. Reach her at skeown@fredhutch.org.

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