For someone whose work hours add up to a self-described "job and a half," you might expect some weariness or stress. Not so for Dr. Paul O'Donnell. "I can't wait to get to work each day," he says of his activities for the Seattle Cancer Care Alliance as an oncologist and medical director of the Inpatient Transplant Service and as a researcher in the Clinical Research Division. "There's joy in doing what gives you deep satisfaction. I feel fortunate to have a rewarding job that is so engaging and intellectually stimulating."
He may feel fortunate, but it wasn't the winds of chance that landed O'Donnell at the Hutchinson Center four years ago. That step was the latest in a series of life-changing, never-look-back decisions, and it's indicative of the passion, determination and intelligence that O'Donnell brings daily to his roles.
No matter which of those three jobs he's doing at a given moment, his scientific perspective is constant. "In research, administration and patient care, it's all about making observations, interpreting them and then making hypotheses about how things work and how to make things better. I switch modes, but I don't really change my approach."
O'Donnell and colleagues are at the forefront of promising research using alternative donors for bone-marrow transplantation. For many people who need a transplant, it may be difficult or impossible to find a related or volunteer donor who is a suitable match, especially for non-Caucasian individuals. O'Donnell is working to increase the success of transplants using "half-matched" family members — parents, children and a percentage of siblings who share only one common set of chromosomes. "With this approach, if you have a living parent, child or sibling, you have a donor," he said. "That means virtually anybody has a donor, regardless of ethnicity. It decreases costs, because you don't have to search for a donor and increases the availability."
Like cord-blood transplants, there are many obstacles to overcome with half-matched donors. "It's been a very difficult nut to crack because of the high risk of graft-vs.-host disease (GVHD) and the amount of immuno suppression that's required to control rejection has led to unacceptable rates of infection and death," O'Donnell said.
In any transplant, the immune systems of the donor and recipient collide, and one has to "win." If the recipient's system wins, the graft is rejected. If the donor marrow wins, the graft takes, or engrafts, but especially with half-matched donors, GVHD — a potentially life-threatening complication — tends to be very high.
Making transplants work
To ensure engraftment without severe GVHD, O'Donnell has conducted Phase I/II clinical trials since 1999 in which a half-matched transplant is performed and then a high dose of chemotherapy is administered to the patient three days later. The treatment kills activated immune cells but doesn't harm the stem cells, which are needed to grow the new immune system. The patient is given medications to control GVHD.
In terms of safety, this approach appears to be successful. About 85 percent of the patients engraft, which is a similar rate to matched, unrelated donors, and about half the patients develop mild-to-moderate GVHD, which is no different than any other type of transplant. However, it's not yet known how successful this approach is in curing cancer, and for which types of cancer it would be most beneficial. "We're at the point where we can start to look more disease-specific and try to make changes that are targeted at treatment of particular malignancies rather than just making the transplant work," O'Donnell said.
He and his colleagues next plan to develop a clinical trial using the procedure for Hodgkin's and non-Hodgkin's lymphoma patients. Eventually, they also aim to have a randomized study comparing the success of half-matched donations to cord-blood donations, another area of research focus at the Hutchinson Center.
A life of science
Pursuing a life of science didn't involve careful deliberation on O'Donnell's part. He believes goals are best achieved by plunging ahead without hesitation. "You just have to decide what you're going to do and do it," he said. "When you can make decisions like that, it frees up enormous amounts of internal energy to accomplish what you want to do."
When he was in grade school, O'Donnell recalls receiving pamphlets on various careers. One described chemistry as an occupational option, and without knowing much about it, young Paul decided that was the job for him. Armed some years later with graduate degrees in biochemistry and molecular biology, he spent 20 years as a research scientist at Memorial Sloan-Kettering Cancer Center in New York, studying retroviruses that cause leukemia in mice.
O'Donnell acted with equal decisiveness in leaving that career after cancer suddenly became personal. His wife, Nancy, a fellow scientist at Sloan-Kettering, died of cancer in 1987. "That experience was the reason I left basic science to be more directly involved in caring for cancer patients," he said. "It was a conscious decision to be a physician taking care of cancer patients, not cancer mice." At 42 years old, he enrolled at the Johns Hopkins School of Medicine, one of the nation's most prestigious medical schools. He pursued an oncology fellowship there and later joined the faculty.
More than a decade later, O'Donnell pulled up his East Coast roots and began a new phase of his career at the Hutchinson Center. As medical director of SCCA's inpatient program, he's responsible for the quality of care from the medical team. He oversees about 45 medical staff members, including attending physicians, mid-level providers and oncology fellows.
"This tier of medical directors is part of the organizational structure that's designed to make sure we're meeting standards and looking for quality improvement," O'Donnell said. He partners with the nurse-managers to develop and implement policies. He also ensures consistency in the way the transplant service is run; no small task with over 20 physicians caring for patients.
"It's exciting to be involved at this level," he said. "There are always refinements, ways to make the organization function better. I want the inpatient program to be the best there is in the United States."
"Paul is a superb clinician with a passion for quality care," said Dr. Marc Stewart, SCCA medical director. "He has brought to the SCCA the evolving 'science' of quality improvement and has taught us to be more rigorous in our efforts to improve the care we deliver to our patients."
The role O'Donnell most cherishes is working with patients. "I feel like I accomplish more in one day of taking care of cancer patients than in my whole previous career," he said. "These patients who are willing to be participants in clinical research are really very special. They're unique in being willing to take risks. They want to be helped, of course, but they're also helping advance knowledge."
Living through his wife's struggle with cancer has given O'Donnell a wise and empathetic perspective as a care provider. As much as he wants to save patients' lives, he understands that's not always the whole picture.
"Probably one of the hardest things in oncology is to know when you've done enough treatment-wise," he said. "It's hard for young physicians to know when to stop."
Changing standards of care
"Sometimes I see patients who would be much better off at home, being with their families, than going through one more treatment. For that infinitesimal chance that they might benefit, it may not be worth it. Part of being an oncologist is helping people be as realistic as possible."
For O'Donnell, the challenges of patient care, leadership and clinical research have coalesced into a satisfying second career at the Center. "The whole purpose of this place is to improve how things are done and to really expand the option of treatment for the widest possible audience," he said. "We have the opportunity to essentially change standards of care."