Successful Mini-Transplant by Medical College Doc
Gives New Hope to Blood and Bone Cancer Patients

Feb. 25, 2005 - In September 2001, Jonell Shoemaker began experiencing unexplained bruising. Her doctor referred her to Froedtert & The Medical College of Wisconsin, where physicians diagnosed her with acute myeloid leukemia and recommended an intriguing new therapy.

They proposed attacking the cancer with the power of the immune system. Not her immune system—someone else's.

The therapy is known as a non-myeloablative transplant or, more commonly, a mini-transplant. It's a twist on the conventional blood and bone marrow transplants that have been part of cancer care for decades.

Tantalizing Side Effect

Blood and marrow transplants were introduced in the 1960s as a follow-up to high-dose chemotherapy treatment. Because high-dose chemotherapy destroys not only cancer cells, but the patient's bone marrow and immune system as well, the only way to rebuild this crucial system after treatment is to give the patient an infusion of adult blood stem cells or bone marrow cells.

With a standard bone marrow transplant, donor cells have the advantage of being able to attack cancer, but they can also cause Graft Versus Host Disease (GVHD). With GVHD, donated blood cells attack the patient.

From the early days of donor cell transplants, physicians wrestled with the sometimes-deadly symptoms of GVHD, but they also noted one tantalizing side effect: Patients who receive donor cells are more likely to remain cancer-free. Eventually, researchers discovered why: Although donor cells can attack the patient, they also attack any leftover cancer cells.

Physicians soon realized that harnessing this reaction would create a new way to fight cancer. The idea of the mini-transplant was born.

Waiting for a Reaction

After she was diagnosed, Shoemaker sought out several second opinions around the country and spent time investigating her options. By searching the medical literature she learned, "When it came to mini-transplants, I found Froedtert & The Medical College of Wisconsin was on the cutting edge in research and treatment." She decided Froedtert was the place to be.

Her physician was Mary Horowitz, MD, MS, Robert A. Uihlein, Jr. Professor of Hematologic Research and Professor of Medicine (Neoplastic Diseases and Related Disorders). According to Dr. Horowitz, step one of a mini-transplant is a very low dose of chemotherapy or radiation. The purpose is not to kill the cancer, but simply to suppress the patient's immune system so the donated blood or marrow can go to work. After this initial dose, the patient receives the donated cells through an IV infusion.

"This is a high-risk time for the patient," said Dr. Horowitz, who thinks a better term for the therapy is reduced-intensity transplant. To help make sure the immune reaction does not get out of control, the patient takes anti-rejection drugs and other medications. Everyone watches for signs of GVHD.

Gradually, said Dr. Horowitz, donor cells repopulate the blood system, hopefully destroying any cancer cells. The whole process takes six to twelve months.

Matching Tissue Types

A crucial issue with mini-transplants is finding a suitable donor.

Shoemaker was among the 30 percent of people who have a sibling with a sufficiently close "tissue type." Another 30 to 40 percent of patients can be linked with an unrelated donor. The remaining patients are ineligible for the treatment.

Since the cancer-killing effect of a mini-transplant is gradual, the therapy is best suited to slow-growing malignancies. It is often recommended for older people who are not strong enough for high-dose chemotherapy.

"To date, the diseases we can treat with a mini-transplant are still a small portion of all cancers," said James Wade, MD, MPH, Professor of Medicine, Chief of Neoplastic Diseases and Related Disorders and Mariette C. and Philip W. Orth/Tom Anderson Professor of Neoplastic Diseases at the Medical College of Wisconsin, who was a member of the 1997 team that performed the world's first mini-transplant at the Fred Hutchinson Cancer Research Center in Seattle. He said the therapy has proven effective for blood cancers like leukemia, lymphoma and multiple myeloma.

Awesome Feeling

Shoemaker has been off anti-rejection medications since April 2003 and is now in complete remission. A retired pediatric occupational therapist, she now volunteers one day a week at Kathy's House. She said her biggest contribution is providing encouragement to cancer patients just starting treatment:

"I am able to say that I went through it—and that there are a lot more good outcomes than there used to be."

Source:
Cancer Center News
Froedtert Today. November 2004.