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Bone marrow transplants trace roots to UW-Madison 50 years ago

August 19, 2018
Sondel

Bone marrow transplants, used routinely for leukemia and other diseases, worked only in identical twins until the first successful transplants involving other siblings as donors took place 50 years ago in Madison and Minneapolis.

Dr. Fritz Bach, a UW-Madison geneticist, developed a lab test to see if donor and recipient cells matched. The test allowed Bach and Dr. Robert Good of the University of Minnesota to give two young boys who had serious blood disorders healthy immune systems from their sisters in August and September 1968.

By the 1980s, bone marrow transplants took off as a treatment and frequent cure for leukemia, even using unrelated donors. Today, about 15,000 of the transplants are done annually in the U.S., and the procedures have paved the way for other cancer immunotherapies.

The breakthroughs in Wisconsin and Minnesota five decades ago “completely changed the history of bone marrow transplants,” said Dr. Richard O’Reilly, head of the pediatric bone transplant program at Memorial Sloan Kettering Cancer Center in New York.

“They opened up the possibility of cure for a large number of diseases,” said O’Reilly, who helped care for the Minnesota recipient in 1968 and afterward. “They showed that normal cells could do extraordinary things.”

Bill Yerges, of McFarland, a nurse at UW Health, was an early beneficiary of the accomplishment, receiving a bone marrow transplant for leukemia at UW Hospital in 1985 at age 11.

Now 44, Yerges remains cancer free, with only minor side effects from his treatment. As a nurse, he has treated many bone marrow transplant patients. Away from work, he hikes, hunts, fishes and plays baseball with his two sons, ages 8 and 9.

“I’m not limited in my ability to do 95 percent of the things I would want to do,” he said. “I feel very honored to work alongside many of the individuals who developed (the procedure).”

Test-tube transplant

In the 1960s, as organ transplants were catching on, doctors succeeded in doing bone marrow transplants — infusions of blood-forming cells from donors — using recipients’ identical twins.

Attempts involving other types of donors failed because the donors and recipients weren’t genetically identical.

A French researcher, Dr. Jean Dausset, discovered genetic compatibility markers called human leukocyte antigen, or HLA. Bach devised a test — called mixed leukocyte culture, or MLC — in which white blood cells from a potential donor were mixed with white blood cells from the recipient to see if they reacted.

“It was the equivalent of a transplant in a test tube, which nobody else had done before,” said Dr. Paul Sondel, a pediatric oncologist at UW Health who joined Bach’s lab as a student in 1969.

In 1968, Bach used the test on family members of David Zeissett, a 2-year-old boy from New York with an immune disorder called Wiskott-Aldrich Syndrome. The test showed one of David’s sisters would be a good match.

On Aug. 23, Bach and his colleagues injected immune cells from the sister’s bone marrow into David. The transplant failed. David, whose immune system was thought to be too weak to react against the cells, surprised doctors by rejecting them, Sondel said.

His sister’s cells were given to him again on Sept 27. This time, doctors gave the boy an immunosuppressant drug, and the transplant worked.

The Minnesota procedure took place Aug. 24. It was a success, though the patient — a months-old boy named David Camp — ended up needing a second transplant a few months later.

Bach and Good announced their achievements on Nov. 9, with the news appearing around the country, including atop the front page of the Wisconsin State Journal, the next day. On Dec. 28, the doctors published the cases simultaneously in the medical journal The Lancet.

Zeissert, the Madison patient, lived until his late 30s, dying in 2004 from hepatitis C, which he may have acquired from a blood transfusion, said O’Reilly, who was involved in follow-up care for both patients.

Camp, the Minneapolis patient, is alive and has children, O’Reilly said. He declined to say where Camp is living, saying Camp prefers to remain private.

Immunotherapy

Bach, who left UW-Madison in 1980 for the University of Minnesota and later Harvard Medical School, died in 2011 at age 77.

In 1979, the first successful bone marrow transplant using an unrelated donor for a patient with leukemia was performed at Fred Hutchinson Cancer Center in Seattle.

“Major medical centers all over the world started doing bone marrow transplants for leukemia, and the numbers grew exponentially from there,” Sondel said.

A puzzling development ended up spurring interest in other kinds of cancer immunotherapy, he said.

Leukemia patients who received immune cells from matched donors did better than those whose donors were identical twins. That led to the understanding that a small amount of reactivity between donors and recipients leads donor immune cells to attack the recipient’s leukemia, a welcome effect.

Today, some immunotherapies use donor immune cells, while others manipulate a patient’s own immune cells to better recognize their cancer.

One of the latter type of treatments is chimeric antigen receptor, or CAR, T cell therapy, which this year became available at UW Hospital. It uses an HIV-like virus to genetically modify patients’ T cells to target their leukemia or lymphoma.

“These are all conceptually related to the demonstration that the bone marrow transplant worked because it was the immune cells killing the cancer,” Sondel said.

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