For almost as long as there has been a Fred Hutch, there has been a Fred Appelbaum.
A key member of the team that developed bone marrow transplantation as a successful treatment for leukemia nearly half a century ago, Frederick Appelbaum, MD, was honored on Feb. 18 with a Lifetime Achievement Award from the American Society for Transplantation and Cellular Therapy at the organization’s annual meeting in Orlando, Florida.
“These are my peers. These are the people that I’ve been working with my whole career,” he said in an interview in advance of receiving the award.
Appelbaum is an oncologist and executive vice president of Fred Hutchinson Cancer Center, where he holds the Metcalfe Family/Frederick Appelbaum Endowed Chair in Cancer Research. In the course of his career, he has witnessed a transplant procedure once performed by him and just a handful of Seattle physicians win widespread acceptance and international acclaim. Worldwide, more than 1.5 million patients have had these potentially lifesaving interventions.
In the 1970s, Appelbaum was a young researcher at the National Cancer Institute, in Bethesda, Maryland, when his success with an experimental bone marrow transplant procedure caught the eye of E. Donnall Thomas, MD, in Seattle.
Thomas, of course, was a founding faculty member at Fred Hutch. He had been experimenting with bone marrow transplantation since the 1950s and eventually moved his work to the University of Washington. Then, he drove the successful development of the technique at Fred Hutch, which formally opened its doors in 1975. He would be recognized as the father of bone marrow transplantation when he received the Nobel Prize in Physiology or Medicine in 1990.
As a second-year medical student at Tufts University in 1970, Appelbaum remembers, he picked up a journal article by Thomas and his colleague, Rainer Storb, MD, about achieving leukemia remissions through bone marrow transplantation. He often cites that moment as one that transformed his life.
“I read that paper and it was like having my brain tattooed,” Appelbaum said. At the time, blood cancers such as leukemia were, almost invariably, rapidly fatal. Now, he was reading of a dramatic procedure that could be curative. He earned a fellowship at the National Cancer Institute, where he began working on a team exploring new kinds of bone marrow transplants.
Appelbaum was lead author in 1978 of an NCI paper describing the first successful use of “autologous” transplants in which patients with lymphomas had their immune systems restored with samples of their own marrow that had been removed and preserved in a freezer, before their treatment with high-dose therapy began.
Not long after that paper came out, his phone at the NCI rang, and at the other end of the line was Thomas himself.
“Don was not exactly one for chit chat,” Appelbaum recalled. “He said they had a position in Seattle and was I interested in interviewing for it. The call lasted about one minute. … I arranged to go out there and accepted the job on the spot.”
In the years after he arrived in 1978, Appelbaum has played a key role in improving the safety and success of transplantation for a variety of blood cancers and disorders.
As he rose to become a member of the Fred Hutch leadership team, Appelbaum helped to expand the scope of research and treatment there to cover the full range of cancers, including solid tumors of the breast, lung and brain. At the same time, the institution built up its expertise in cancer prevention, epidemiology and in viral diseases ranging from HIV to COVID-19.
The lifetime achievement award was presented to him in Orlando by ASTCT’s president, Brenda Sandmaier, MD, herself a Fred Hutch expert on blood cancers. She began her own career as a research fellow in Appelbaum’s lab in 1986.
Interviewed prior to the meeting, Sandmaier said that when Appelbaum was nominated for this highest honor by a member of ASTCT — who is not connected with Fred Hutch — the awards committee “immediately jumped in” to support it.
“He is a lifelong transplanter. We know he’s receiving this award for all he has done for science, for patients and for this society,” Sandmaier said.
She described Appelbaum as “intellectually curious about science and biology, and very much an advocate for patients.”
Appelbaum is the fifth Fred Hutch scientist to receive the honor. John Hansen, MD, an immunologist and key player on Thomas’s team of researchers, was selected in 2002. Thomas himself received his lifetime achievement award in 2004; Storb in 2008; and Effie Petersdorf, MD, who holds the Madeline Dabney Adams Endowed Chair in AML Research, in 2022.
When Appelbaum began his research career, leukemia was still one of the most dreaded of cancer diagnoses. Transplantation, and the development of more effective chemotherapies with refined dosing regimens, have vastly improved the odds for leukemia patients. At Fred Hutch, he said, clinical researchers also continually improved transplantation outcomes with incremental innovations, many of them among those who provide supportive care to recovering patients.
“Anti-emetics, to reduce nausea, were huge early on when patients were getting their drugs,” he said. Until those medications came along, patients had to be heavily sedated, and in addition to making patients so uncomfortable that they balked at new rounds of chemo, the sedation also made them vulnerable to aspiration pneumonia, with lethal consequences, Appelbaum explained.
Infectious diseases were also a severe problem, quickly taking the lives of as many as 30% of transplant patients due to the weakened state of their recovering immune systems. But researchers were able to identify key microbes — such as cytomegalovirus — and prescribe more effective antimicrobial drugs. Those therapies have reduced, but not yet eliminated, the danger of infectious agents to transplant patients.
The invention of the of the Hickman catheter, by Fred Hutch nephrologist Robert Hickman, MD, enabled caregivers to give patients fluids, medications and nutrition through the same intravenous site, liberating patients from what Appelbaum called the “nightmare” of needlesticks that made patients suffer and doctors struggle to find veins.
'Using the immune system is absolutely going to be necessary to cure these diseases, and cellular therapy right now is the most effective way of using the human immune system.'
— Dr. Fred Appelbaum, Executive Vice President , Fred Hutchinson Cancer Center
In the past decade, the ever-improving triad of bone marrow, blood stem cell and cord blood transplant procedures has spawned a new generation of living, “cellular” therapies. The cells implied in that name are blood components of the immune system, such as T cells and natural killer cells, that can be genetically modified to target a widening circle of blood and solid organ tumors. “Living drugs,” such as CAR-T and adoptive T-cell therapies, along with combinations of drugs that overcome cancer’s ability to shield itself from immune attack, are raising tantalizing prospects for cures.
Acknowledging the shift, the American Society for Bone Marrow Transplantation changed its name to the American Society for Transplantation and Cellular Therapy in 2019.
“Using the immune system is absolutely going to be necessary to cure these diseases,” Appelbaum said. “And cellular therapy right now is the most effective way of using the human immune system.”
He sees in the future that cellular therapies will become as effective against solid tumors as they are today against certain blood cancers, and that eventually it may no longer be necessary to remove blood cells and modify them in the lab, before restoring them to the patient. Instead, the person might be injected with viral vectors containing the genetic instructions to make the required modifications of immune cells, without the costly laboratory equipment needed to re-engineer cells outside the body for such treatments today.
For years, Appelbaum was director of Fred Hutch’s Clinical Research Division, which carried out research in bone marrow transplantation and in the development of cellular therapies. In 1998 he led the creation of a partnership with UW Medicine, Fred Hutch and Seattle Children’s to launch the Seattle Cancer Care Alliance, which opened it seven-story daytime treatment clinic on the Fred Hutch campus in 2001. Appelbaum was its president and executive director from its formation until 2016.
Last year, Fred Hutch and SCCA merged into a single independent nonprofit organization that also serves as the cancer program for UW Medicine, and next month will open a new, 150,000 square foot facility to expand its 22-year old South Lake Union Clinic.
For Appelbaum, the merger and opening of the new clinic effectively complete a vision he has held for decades.
“I think this is where we always wanted to be,” he said. “I just took a tour of the new building, and it is amazing.”
Appelbaum received his Lifetime Achievement award at a time when he has been reflecting on the legacy that he and his colleagues built at Fred Hutch. In May, he will publish Living Medicine, a history he wrote about Fred Hutch’s role in the development of bone marrow transplantation and cellular therapy.
Despite 50 years of work in medicine, the ever self-effacing Appelbaum still pinches himself to think about his role at Fred Hutch and to be honored by his peers for a lifetime of achievement.
“I’m very happy and I’m very pleased and it’s all worked out great. But you know, it’s all luck. It just is,” he said.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.
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