Mini-transplantation, one of Storb’s proudest achievements, uses a gentler regimen (known as non-myeloablative conditioning) and has enabled older blood cancer patients to receive bone marrow transplants. But it grew out of a mistake.
In a preclinical model of BMT, some of the animals had been mistakenly given a lower dose of radiation than normal — but the donor stem cells still engrafted in a few. Storb wanted to explore the concept, but initially couldn’t get NIH funding for his off-the-wall idea. Seed money from the grateful father of a patient got him started.
Patients receiving a standard BMT undergo a grueling pre-transplant regimen and spend weeks in the hospital. The first patient who received a mini-transplant, for chronic lymphocytic leukemia, “Didn’t even see a hospital from the inside,” Storb said. “He was totally outpatient, he didn’t even lose his hair.”
At the time, “the old age in transplant was 55, which was the upper limit of what we were transplanting at the time — until this disruptive paper came out,” said Stanford University transplant researcher Judith Shizuru, PhD, who joined the network of researchers, assembled by Storb, to move the concept of non-myeloablative conditioning regimens forward.
“Someone else might [look at that experiment and] say, ‘Oh that’s not quite what I wanted,’ and ignore that interesting finding,” said Fred Hutch bone marrow transplant researcher Brenda Sandmaier, MD, who has worked closely with Storb since she joined Fred Hutch in the mid-1980s. Sandmaier is deputy director of Fred Hutch’s Translational Science and Therapeutics Division.
“But instead he said, ‘This is very interesting. I want to look at this, I want to investigate it,’” Sandmaier said. “To me, it’s very illuminating on how you do science. You have a hypothesis and you think you’re answering the question — but if you get some strange result, you don’t ignore it.”
Storb’s interest in mini-transplantation was also inspired by work he had published in 1979, the first large-scale study detailing the ability of donated cells to stave off leukemia relapse. Mini transplants rely on donated immune cells, rather than harsh drugs and radiation, to kill off cancer cells.
In the late 1970s, BMT researchers were more concerned with controlling the often-deadly graft-vs.-host disease, or GVHD, than capitalizing on graft-vs.-leukemia, or GVL. But as transplant improved and technologies advanced, the finding helped inspire not only the mini-transplant, but today’s cellular cancer immunotherapies.
The early days, however, were very low-tech.
“We did a lot of stuff with our own hands and that’s I guess what helped us with translating [the preclinical work to patients],” Storb said. He and colleague Bob Epstein spent time treating transplant patients “and that helped us in understanding where things were still going wrong, and we took that back to the lab. Being a physician-scientist was critical.”
Symposium speakers noted the consistent quality of Storb’s output. Just last year, Storb and collaborators led by Fred Hutch’s Masumi Ueda Oshida, MD, MA, tackled a long-standing question about whether mutations in donor cells are likely to drive accelerated cell growth and eventually leukemia. They found that donated cells don’t acquire mutations at a higher rate in recipients than donors, and even cells from the youngest donor in the study (age 12) harbor genetic changes associated with cancer. But these changes don’t cause a higher risk of disease later, according to the work, published in Science Translational Medicine.
Mentor: warm and welcoming
As long as he has been a scientist, Storb has also been a trusted resource for his colleagues.
“He’s persuasive, persistent — perhaps almost to a fault,” Mielcarek said, who credits Storb and his late wife, Beverly Torok-Storb, PhD, as his “scientific parents.” Storb made sure mentees published their work, even the negative results, to ensure that every experiment or clinical trial enriched the field, Mielcarek said.