An NCI-designated Comprehensive Cancer Center
By Abe Rosenberg | May 7, 2019
This story is part of a series that explores the success of City of Hope’s bone marrow transplant program, which recently performed its 15,000th transplant.
“How old are you?”
Julia O'Neil did not like hearing that question.
At age 67, the grandmother from Palos Verdes, California, was diagnosed with acute myeloid leukemia (AML). She went through two rounds of chemotherapy and was now seeking a stem cell transplant. But when doctors asked about her age, it was troubling to think some arbitrary number might rule her out for a lifesaving procedure.
“Needless to say, I was upset to hear that news,” she recalled.
O'Neil turned to City of Hope. There she met Ryotaro Nakamura, M.D., associate professor of hematology and hematopoietic stem cell transplantation, who made it clear that choosing (or not choosing) transplant candidates based solely on their age was an idea that's, frankly ... old.
“Age by itself is not considered an exclusion anymore,” said Nakamura. “There's no 'too old' nowadays.”
In fact, City of Hope has successfully performed transplants on patients into their late 70s. Nationwide, there are reports of patients as old as 80 undergoing the procedure.
In the past decade, several studies have confirmed that, properly handled, seniors who receive stem cell transplants can see survival rates comparable to that of younger patients.
“When we select [older patients] carefully, the results are the same [as with younger patients],” he said.
But what is “proper” handling? What is “careful” selection?
The answer, Nakamura explained, has three parts:

Assessing Risk

Years ago, it was assumed that older patients couldn't handle the rigors of a transplant because their systems weren't strong enough. Today, while age is no longer the determining factor, neither is it ignored.
But physiological age matters more than chronological age. And that requires careful measurement.
“We want to know a patient's organ function reserves,” said Nakamura. “The heart, the lungs, the liver, the kidneys. We can test these things and get a snapshot, and many older patients test well.
“It's important to see how well a patient can bounce back from a stressful situation. So, for example, we give everyone over 65 a cardiac stress test, even if they're symptom-free.”
But stress manifests in many ways, so Nakamura strongly supports a full geriatric assessment, taking into account a person's activity level, any known medical problems, his or her social and support network and overall fitness and nutrition levels.
“The more we know about the patient,” he said, “and the more ways we can measure, the more our evolving confidence goes up.”

Reducing Toxicity

Traditionally, doctors prepared a patient for transplant by administering massive doses of chemotherapy to destroy the bone marrow. “The more chemo you give, the more [cancer] cells die,” said Nakamura.
This procedure can carry a serious risk of organ damage, especially in older patients. But it may not be necessary.
For 20 years now, Nakamura and his colleagues have employed “reduced intensity conditioning.” RIC uses lower doses of less toxic chemotherapy, not destroying the immune system but suppressing it enough to allow the transplant to take root.
The results have been encouraging, and Nakamura continues to refine the process. A recent study looked at senior transplant patients who were given RIC using the chemotherapy drug Melphalan. More than 95 percent of those transplants worked, and there was no significant jump in relapses or complications.

Improving Efficacy

What happens right after a transplant may be just as important as the transplant itself. To ward off graft-versus-host disease (GVHD), patients with a less-than-perfect donor match are usually given a high dose of the chemo drug cyclophosphamide to deplete donor T cells.
Nakamura is trying this with older patients who received RIC before the transplant. The combination appears to maintain the transplant's effectiveness, allowing the patient's immune system to recover, while minimizing complications down the road.
All this was laid out for O'Neil, but at no time did anyone question her suitability for a transplant due to her age. “Dr. Nakamura and his team were wonderful. I can't say enough about them,” she said.
Her transplant went well, thanks in large part to a perfect donor match from her younger sister. O'Neil spent four weeks in the hospital and coped with a mild case of GVHD about a year later. Today, six years after the procedure, she feels “fantastic! Almost 100 percent back to normal. And I count my blessings every minute.”
Bottom line — O'Neil and Nakamura offer the same message to senior patients wondering about the pros and cons of a stem cell transplant.
“Don't be scared,” said Nakamura.
“You can do it!” echoed O'Neil.

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