Froedtert Today

March 2007 Issue

"I Never Felt I Wouldn't Keep Going"

Physicians and staff in the Hematologic Malignancies Program and the Blood and Marrow Transplant Program at Froedtert & the Medical College of Wisconsin work together to offer advanced treatments for patients with cancers of the blood, bone marrow and lymph nodes.

On Dec. 21, 2006, Paula Didier, 47, of West Bend, enjoyed a special piece of cake at Froedtert & the Medical College of Wisconsin. The cake, presented by Paula and her husband, Jim, to staff in the Hematology and Oncology Clinic, marked a very special day: the one-year anniversary of Paula’s second stem cell transplant to treat acute myeloid leukemia (AML). Despite a three-year battle with AML, Paula considers herself to be very fortunate.

AML, a cancer of the blood and bone marrow, is one of four major types of leukemia, accounting for about one-third of about 35,000 new cases of leukemia each year (American Cancer Society 2006). In leukemia, the bone marrow produces abnormal white blood cells (leukemia cells), which crowd out the normal cells (white blood cells, red blood cells and platelets) in the blood.

AML is one of many types of hematologic malignancies — cancers of the blood, bone marrow and lymph nodes. Others include:

Chronic leukemia
Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma
Multiple myeloma
Myeloproliferative disorders
Myelodysplasia

“In most cases, we don’t know the causes of these diseases,” said Jared Klein, MD, Medical College of Wisconsin medical oncologist and director of the Blood and Marrow Transplant Program. “Many of these disorders occur as people age, but they also occur in children.”

Medical College physicians and other team members provide highly specialized care through the Hematologic Malignancies Program. “All of the physicians have a primary disease focus,” said James Wade, MD, Medical College of Wisconsin medical oncologist and chief, Neoplastic Diseases and Related Disorders. “For example, a physician may specialize in treating primarily leukemia or lymphoma. They’re truly specialists; all they do and think about — day in and day out — is a particular type of cancer, and this expertise truly benefits patients.” In addition, nurse practitioners and physician assistants specialize in specific diseases and provide continuity as patients move between inpatient and outpatient care.

Seeing “Stars”

An avid exerciser, Paula has always enjoyed step aerobics, yoga and walking on a treadmill. In late 2003, however, she began having trouble during her workout sessions. “It wasn’t real obvious that I was sick, but I saw stars as I exercised,” she said. In February 2004, Paula learned that she had AML; her physician referred her to Froedtert & the Medical College for treatment.

“The doctors gave me lots of information about the disease as well as my options,” Paula said. “We knew we could deal with it.”

Under the care of Parameswaran Nair Hari, MD, MRCP, Medical College of Wisconsin medical oncologist, Paula received two rounds of chemotherapy over six weeks. After the second round, her disease was in remission (the disappearance of the signs and symptoms of cancer). Paula returned home and continued working part-time as a materials engineer at Harley-Davidson, taking time for additional chemotherapy treatments and recovery over the next few months.

Based on her type of disease, the next step in Paula’s treatment was a blood stem cell transplant.

Blood and Marrow Transplant Program

The Blood and Marrow Transplant Program at Froedtert & the Medical College is a regional and national leader in blood and marrow transplantation. The program performs more blood and marrow transplants each year than any other hospital in Wisconsin. Patients are offered the complete range of transplant therapies, including treatments available through clinical trials.

“We’ve gathered a strong team of specially trained and dedicated health professionals with a high level of expertise in performing blood and marrow transplants,” Dr. Klein said.

Stem Cells Used for Transplants

A stem cell is a cell from which other types of cells develop in the body. Blood-forming stem cells, found in the bone marrow, give the body a constant source of new red blood cells, white blood cells and platelets that carry oxygen, fight infection and prevent bleeding. Blood-forming stem cells may be obtained from three sources: marrow, circulating (peripheral) blood and umbilical cord blood — collected from the umbilical cord and placenta after a baby is born. (Donated cord blood is used mostly to treat children.)

When a patient’s bone marrow has been destroyed by disease, chemotherapy and/or radiation, a stem cell transplant can provide new blood-producing cells. In a relatively simple procedure, the healthy stem cells (from the patient or a donor) are infused through a vein, where they enter the bloodstream and migrate to the bone cavities. Within a short time, the stem cells begin producing normal blood cells. Depending on the source of the stem cells, the procedure may be called a bone marrow transplant, a peripheral blood stem cell transplant or a cord blood transplant.

Why and When to Transplant

A blood or marrow stem cell transplant may be used as therapy for certain hematologic cancers. In some cases, a transplant is used to cure the disease; in other instances, it may prolong and improve the quality of life.

One reason transplants are used is to make it possible for patients to receive very high doses of chemotherapy and/or radiation to kill cancer cells.

“When a patient receives high doses of chemotherapy and/or radiation therapy to kill cancer cells, these treatments also kill many normal cells, including bone marrow cells,” Dr. Wade said. “Blood and marrow transplantation is used to replace the marrow cells that were destroyed. This is done in two ways: removing a patient’s own stem cells before chemotherapy and/or radiation and then returning the stem cells to the patient (an autologous transplant), or transplanting cells from a donor to the patient (an allogeneic transplant).”

“The decision to do a blood or marrow transplant depends on many factors, and the decision process changes as new approaches to transplant and other treatments come along,” said Christopher Bredeson, MD, Medical College of Wisconsin medical oncologist and director, Hematologic Malignancies. “The transplant process has changed. We look at who can tolerate what type of transplant and if the treatments to control the disease before transplant can be tolerated.”

“A blood stem cell or marrow transplant is not a ‘last ditch’ effort,” Dr. Klein said. Transplants are commonly used to treat leukemia and lymphoma, and are most effective when these diseases are in remission.”

“We base the decision on the type of transplant on a patient’s age, disease and other health problems the patient may have,” Dr. Wade said. “Not all leukemias are the same and not all lymphomas are the same. We develop goals for each patient, based on his or her disease and wishes. We think of the best options from the time of diagnosis throughout the course of the disease. The goal is to use therapies that provide the best result with the least amount of toxicity.”

Types of Transplants

The Froedtert & the Medical College Blood and Marrow Transplant Program is the only program in the state to provide three types of blood and marrow transplants.

An autologous transplant uses the patient’s own stem cells (or cells from an identical twin). Before receiving chemotherapy to destroy cancer cells, a patient’s stem cells are saved. The stem cells are then returned to the patient after treatment to supply the bone marrow with fresh, blood-producing cells.

An allogeneic transplant uses donated blood or marrow cells. Donors may be related to the patient (usually a sibling) or unrelated, but must have a tissue type that matches the patient. Tissue type refers to a group of proteins on the surface of the stem cells. With the help of the National Marrow Donor Program®, doctors find donors whose stem cells match the patient’s own stem cells as closely as possible.

A non-myeloablative transplant or “mini transplant” is a newer type of allogeneic transplant that relies on immune reactions to fight cancer. The patient receives low doses of chemotherapy — not enough to destroy the cancer or all of the bone marrow, but enough to suppress his or her immune system. Then the patient receives donated stem cells which, over a few months, replace the patient’s own bone marrow cells. The new stem cells develop an immune reaction to the patient’s cancer and kill off the cancer cells, which is call graft-versus-tumor effect.

The “mini transplant” was developed in the 1990s for people over age 50 and those who have other medical problems that could lead to complications from transplantation. The Blood and Marrow Transplant Program is the only one in the region that performs this type of transplant.

Graft-versus-tumor effect is a benefit associated with a donor transplant. “Even if donor cells are matched, they are different from the patient’s cells,” Dr. Wade said. “Donor cells can identify abnormal cells and kill them — this is what a healthy person’s immune system does every day. Once the donor’s infection-fighting cells are established in the patient’s body, they recognize any remaining cancer cells as being foreign and destroy them.”

“Studies have shown that if we prepare a patient with this less intensive therapy upfront, the donor blood stem cells will grow and destroy the remaining cancer cells in the patient,” Dr. Wade said. “The non-myeloablative transplant relies more on this remarkable ability of donor stem cells to help destroy cancer cells.”

A possible side effect of an allogeneic transplant, however, is graft-versus-host disease (GVHD). This occurs when white blood cells from the donor (the graft) identify cells in the patient’s body (the host) as foreign and attack them. To prevent life-threatening GVHD, patients receive medications to suppress their immune system. The Blood and Marrow Transplant Program at Froedtert & the Medical College pioneered allogeneic transplant techniques, especially a process to treat donated stem cells to reduce the risk of GVHD.

“We use peripheral blood stem cells for autologous transplants; these tend to grow faster,” Dr. Klein said. “For allogeneic transplants, we use marrow and blood stem cells, but we use marrow stem cells when there’s a concern about how well a donor matches the patient and the likelihood of graft-versus-host disease.”

Paula’s First Stem Cell Transplant

While Paula was still in remission, in August 2004 she underwent preparation for an autologous stem cell transplant. First, she received medication to stimulate the release of stem cells from her marrow into the bloodstream. Her peripheral blood stem cells were collected over three days using apheresis, a process that removes blood from the body, separates out a particular blood component and returns the blood to the body. Her stem cells were then frozen.

Next, Paula received high doses of chemotherapy over a few days to kill the cancer cells. (The chemotherapy also destroys normal cells, including bone marrow.) She rested for a day to clear the chemotherapy from her body. Her collected stem cells were then thawed and cleaned before they were returned to Paula intravenously on Sept. 1. The cells eventually settle in the bone marrow and begin to grow, replacing the cells destroyed by chemotherapy.

Over the next few weeks, Paula received care in the Blood and Marrow Transplant Unit, where she coped with side effects — nausea, pain and bleeding — of the intense chemotherapy. She returned home and, in early November, returned to work.

Paula’s Second Stem Cell Transplant

Paula’s blood was tested every two weeks, and her bone marrow was tested three months after the transplant. “I was feeling really good,” she said. In May 2005, however, she learned the AML had returned. “They caught it as it was just starting to develop,” she said. In August 2005, Paula came under the care of Dr. Wade.

Following chemotherapy, Paula’s disease once again went into remission, only to return in September. Dr. Wade discussed treatment options with Paula and Jim, and Paula decided to undergo a non-myeloablative or “mini transplant” involving donor stem cells. Dr. Wade searched for a stem cell donor through the National Marrow Donor Program®.

“Because I had been through so many chemotherapy treatments, we considered this type of transplant,” she said. “It was less toxic and less damaging to my organs.”

An unrelated donor was found, as Paula again had chemotherapy to place her disease in remission. This time, her transplant preparation involved receiving lower doses of chemotherapy and radiation to “knock down” her marrow prior to the transplant. On Dec. 20, 2005, Paula received peripheral blood stem cells from the donor. “I was fortunate to find a well-matched donor,” she said. During her recovery, Paula had some nausea but no pain, and returned home on New Year’s Eve. One year later, a bone marrow test showed Paula’s disease remained in remission.

As part of her post-transplant care, Paula has undergone photopheresis treatments twice a week since March 2006. Photopheresis suppresses the donor cells that contribute to the development of graft-versus-host disease. This treatment, not available at many local hospitals, is very helpful for post-transplant management.

“I never felt I wasn’t going to keep going,” Paula recalled. “I had excellent care. The inpatient nurses were very knowledgeable and kept us informed. The staff in the clinic is awesome. We really got to know them, which made it easy. It’s great being around people who respect you enough to tell you everything. And Dr. Wade was a godsend. I felt comfortable knowing he was so well-versed in my condition.”

In addition to physicians, many other team members are involved in the many aspects of blood and marrow transplantation.

“Transplant coordinators help with donor searches and arrange medical evaluations, social workers assist with housing and support for patients, and financial counselors check insurance coverage,” Dr. Klein said. “Dedicated nurse practitioners and physician assistants work with patients in Blood and Marrow Transplant Unit, the outpatient Hematology and Oncology Clinic, the Blood and Marrow Transplant Clinic and the Day Hospital.”

Other team members include pharmacists who specialize in oncology and transplants and laboratory staff who freeze and process blood and marrow products for transplant. The BloodCenter of Wisconsin is an important transplant partner, providing tissue typing and DNA testing for potential donors as well as blood products used by the Blood and Marrow Transplant Program. The Blood Center also provides peripheral blood stem cell collection (using apheresis) and storage for autologous transplants, and photopheresis to modify a patient’s own immune response to his or her disease after transplant.

All transplant procedures take place in the Blood and Marrow Transplant inpatient unit, where staff members help patients remain emotionally comfortable and stay as physically active as possible.

“We have a large team of compassionate, dedicated staff who always consider a patient’s needs,” Dr. Bredeson said. “Because of the nature of these diseases and the transplant process, we see patients for many weeks or months as they undergo life-changing illness and treatments, and staff become very close with patients and their families.”

Patients with hematologic malignancies and other cancers also receive extended outpatient care in the 10-bed day hospital at Froedtert & the Medical College. This special unit provides acute care in an outpatient setting. Patients may spend a few hours in the unit to receive blood transfusions, IV fluids and medications. The day hospital provides care seven days a week. When the new Cancer Pavilion opens in early 2008 at Froedtert & the Medical College, the day hospital will expand to 25 beds.

The Hematology and Oncology Clinic provides outpatient care for patients with hematologic malignancies, pre-transplant patients and post-transplant patients who are far out from their transplant. The Blood and Marrow Transplant Clinic focuses on medical and supportive care for patients with post-transplant complications.

Support for patient and their families is an integral part of the Blood and Marrow Transplant Program. Through patient support groups, patients with blood-related cancers find support and information in a caring environment. Froedtert’s Patient Relations department also offers transportation and housing for patients and families when needed. In addition, nurses offer ongoing education to patients and families in all aspects of care.

Drs. Klein and Bredeson are working to continuing integrating the Hematologic Malignancy Program and the Blood and Marrow Transplant Program to offer the full spectrum of therapies — from chemotherapy to transplant when appropriate — and support.

Research

The Blood and Marrow Transplant Program is actively involved in clinical and research efforts to investigate new treatments for hematologic malignancies. Research efforts have included post-transplant treatments to reduce the effects of graft-versus-host disease, the use of “mini transplants” for older and/or frailer patients, and new treatments for multiple myeloma, leukemia and other diseases.

“Research includes laboratory studies to understand the biology of transplantation, taking information learned in the laboratory to patient care as well as clinical trials of new and evolving therapies,” Dr. Bredeson said. “Our program has the advantage of being at an academic center. We are working to improve transplant outcomes for patients receiving their own cells as well as donor cells. We have the necessary technologies and knowledge to keep this program at the forefront of the transplant field.”

Another component of research is the integration of the Hematologic Malignancies and Blood and Marrow Transplant programs with the Center for International Blood and Marrow Transplant Research (CIBMTR). The Center, housed at the Medical College of Wisconsin, maintains the world’s largest blood and marrow transplant database, under the direction of Mary Horowitz, MD, MS, Medical College of Wisconsin medical oncologist and scientific director of the Center. Data is gathered from hundreds of medical centers in nearly 50 countries, representing up to 16,000 transplant outcomes per year. The Center collects and studies data on the short- and long-term outcomes of patients, the efficacy of different transplant approaches and other issues. The data are available to investigators and physicians worldwide.

The Blood and Marrow Transplant Program

The Blood and Marrow Transplant Program, which began in 1980, provides a full range of blood and marrow transplant procedures. Since 2000, the program has performed 512 transplants. Most patients come from Wisconsin, Illinois and Michigan.