The Cedars-Sinai Blood and Marrow Transplant Program earned top marks from the Center for International Blood and Marrow Transplant Research, recognizing that the program’s one-year patient survival rate exceeds expectations. Cedars-Sinai Cancer’s program is one of only 12 adult transplant programs to achieve this distinction, among a pool of 172 programs.

Expected survival outcomes range from 68% to 83% after one year—lower than the 90% survival rate among Cedars-Sinai patients.

“Our success in hematopoietic stem cell transplantation is due to our outstanding team,” said John Chute, MD, director of the Division of Hematology and Cellular Therapy at Cedars-Sinai. “We are driven by a singular goal: giving our patients the best possible opportunity for a cure, with the least toxicity.”

Patients like Yu, who can now devote his energy to his family and a new chapter in his career rather than fighting cancer, are a powerful inspiration.

“We are honored to be among the top allogeneic transplant centers in the nation,” said Chute, who is the Linda Ostrowski Chair in Hematology/Oncology in honor of Barry Rosenbloom, MD. “We’re most excited to see our patients year after year at their follow-up visits.”

One game-changing shift that dramatically improved survival outcomes: Patients are routinely given cyclophosphamide, a chemotherapy drug, after their transplant (PTCy). The drug helps to prevent graft-versus-host disease (GVHD), a serious complication in which the newly transplanted immune cells begin to attack the recipient’s body. Cyclophosphamide kills the mature T-cells that cause GVHD.

This practice was first used in transplants with cells from half-matched (haploidentical) donors. These donors have human leukocyte antigen (HLA) markers that match half of the patient’s HLA markers. Before PTCy was common, the usual defense against GVHD used a less potent immune-suppressive drug that often caused mouth sores and impaired nutrition when it was needed the most.

PTCy proved so effective, its use was extended to all transplant patients. Clinical trials have now validated PTCy as a superior method to prevent GVHD over the previous standard.

“We were ahead of the curve on this,” Paquette said. “We broadly applied strategies designed for haploidentical transplant patients to all of our patients, with outstanding results.”

In addition to the use of PTCy, Paquette attributes another factor to the improvement in outcomes: turning to younger donors, even if they are not perfect matches.

Traditionally, fully matched sibling donors were the gold standard for stem cell transplants. Half-matched donors were considered risky, due to higher rates of GVHD or the need for complex graft manipulation. Use of PTCy made haploidentical transplants a viable possibility.

“Some people still think a fully matched donor is the best to have, but we started seeing something different,” Paquette said. “In terms of outcomes, we saw our half-matched transplants were doing as well as those who had fully matched, related donors.”

The difference is age, Paquette said.

Often, a fully matched sibling is close in age to the recipient, and the average recipient is in their 60s. The ability to use half-matched donors greatly increases the pool of potential matches, including younger people. A Center for International Blood and Marrow Transplant Research study found younger donors are linked to better outcomes.

“With each decade of life that the donor is above the age of 30, you have a significant decline in the survival of the recipient,” he said. “Now, instead of siblings, we can look to nieces, nephews and even grandchildren.”

A standardized conditioning regimen—an essential phase in the transplant process—also contributed to the program’s success. These regimens wipe out the remaining cancer and reduce the immune system to prime the body for the donor cells.

Paquette and his team evaluated the program’s regimens and phased out the ones most linked to complications. Ultimately, the team has adopted a single routine for all patients that is complementary with PTCy. Every patient receives one chemotherapy drug and full-body radiation. Doses are adjusted based on a patient’s age, the aggressiveness of their disease or other important factors.

“We may be one of only a handful of places in the country that use just radiation and one chemo drug for conditioning all patients,” Paquette said.

This results in easier management, fewer complications and lower toxicity while achieving necessary immune suppression and disease control.

Older adults are the most likely to be diagnosed with leukemia or other hematologic malignancies, but they’re often excluded from transplants due to concerns about risk and recovery. Cedars-Sinai Cancer is developing a study for patients who are 65 and older that addresses those concerns from many angles:

• The team conducts pre- and post-transplant assessments of hand-grip strength, a walk test and neurocognitive testing to track which patients recover well from transplantation—and why.
• They are determining how to adjust the PTCy dosage to reduce complications without increasing risk.
• Because PTCy can affect the heart, especially in older patients, they are conducting MRIs to detect subclinical heart damage that could be connected to the chemotherapy drug.
• They’re investigating the effects of infusing young stem cells into older bone marrow, exploring whether the young cells rejuvenate the aging bone marrow or if the aged environment inhibits the new cells.
• Researchers are collecting stool samples to study the gut microbiome before and after transplant, with attention to the changes in the bacteria and yeast in the intestines, to find connections to immune recovery.

“We want our patients to be as functional as they were going into the transplant—but free of cancer,” Paquette said.

Yu trained for his transplant the same way someone might train for a marathon. He kept up with his exercise routine, and his preparation portion went smoothly. The transplant posed a more challenging series of ups and downs, including a prolonged difficulty obtaining a visa for his cousin to enter the country to donate the lifesaving cells, which delayed his transplant by several months.

In March, he saw Paquette for his one-year checkup.

“The first six months after transplant were rough. Then I started feeling functional, and now at one year, I’m more than functional,” Yu said. “I’m stupendous.”

For now, Yu has hung up his long-distance running shoes, but only due to his busy schedule. He squeezes in plenty of weight-training time and connected family time with Alice and Abel. They’re discovering the joys of parenthood, one milestone at a time.

“I lost the cancer lottery, but I’m lucky in every other respect,” he said.