Cancer: Transplant Therapies Harness Power of Blood and Marrow Cells
Jared Klein, MDMedical College of Wisconsin Medical Oncologist
Director, Blood and Marrow Transplant Program
Transplanted blood and bone marrow cells play a key role in treating many forms of leukemia, lymphoma and autoimmune disease. Jared Klein, MD, explains the history of this fascinating therapy and outlines the different ways physicians use transplanted cells to fight cancer and other devastating illnesses.
Q. What is a blood or marrow transplant and how does it work?Blood and bone marrow contain immature cells that are often referred to as stem cells. The function of stem cells is to make new blood cells, including white cells, red cells, platelets for clotting and lymphocytes to help fight infection.
In the early 1960s, people began to realize you could give an animal a high dose of radiation and you could re-establish the animal’s immune system and bone marrow function by infusing bone marrow cells into the animal. In the early 1970s, E. Donnall Thomas, MD, a researcher in Seattle, first reported using this technique for patients with advanced leukemia who otherwise had no chance of being cured. The technique allowed patients to receive very high doses of radiation and chemotherapy to kill the leukemia and then use bone marrow cells that had been collected from a family donor to re-grow the patient’s bone marrow.
Following this discovery, marrow transplant was applied to other forms of leukemia where there was no cure. As it became more apparent that marrow transplant was effective, the treatment has been expanded to treat patients with other diseases.
Q. What is a “mini-transplant?”One of the early difficulties for bone marrow transplant patients was the problem of graft-versus-host disease (GVHD). This reaction occurs when donated marrow cells see the patient’s cells as being “foreign” and then begin to attack the patient’s normal body cells, including the skin, liver and gastrointestinal tract. The occurrence of GVHD is one of the important reasons the donor and patient must have the same tissue type, or be an “identical match.”
Even today, GVHD remains a major hurdle, but as we wrestled with GVHD, we became aware that it also has some benefits in controlling cancer. We realized donor cells can recognize cancer cells as foreign, and induce a beneficial immune response called graft-versus-leukemia (GVL). A “mini-transplant” uses an approach to harness the GVL effect to control the cancer.
The idea of a mini-transplant is essentially to use low-dose radiation or low-dose chemotherapy to suppress the patient’s immune system. This allows transplanted donor cells to grow and, with time, to recognize the leukemia or cancer as foreign and fight it.
One result of a mini-transplant is that more patients are now eligible for transplantation. Because the severity of high-dose radiation or chemotherapy is diminished, patients who were previously ineligible for a transplant can consider this option. Patients who are less fit, who are older or who have additional medical problems can now safely receive a stem cell transplant.
Q. Is it difficult to find a matching donor?Since you inherit your tissue type from your parents, there is only a one in four chance that you and your brother or sister will be a match. Consequently, there are many people who cannot benefit from a stem cell transplant because they do not have an identical donor.
In 1987, the National Marrow Donor Program was created to enroll people as potential donors. Today, there are more than 10 million people registered. Within the Caucasian population, there is about a 70 percent chance of finding an unrelated donor who is an identical match. It is harder to find a matched donor for African-Americans or Hispanics, because there are fewer such individuals registered in the database.
Q. Is it possible to transplant a patient’s own cells?Yes. Certain tumors like Hodgkin’s disease, non-Hodgkin’s lymphoma (lymph node cancer) and multiple myeloma can benefit from a transplant using the patient’s own stem cells. In those cases, we can collect stem cells from the patient’s own bone marrow or blood and later reinfuse them. This is known as an autologous transplant (as opposed to an allogeneic transplant, which is the term for a donor transplant).
More recently, autologous transplantation has been investigated as a therapy for autoimmune disorders such as scleroderma and multiple sclerosis. The early results of this therapy are very encouraging.
Q. Are you currently investigating any experimental transplant techniques?We have many clinical trials that test different stem cell transplant approaches. One of them is for patients with multiple myeloma. In this trial, we compare the effectiveness of autologous cell transplant (patient’s own blood cells) versus autologous transplant plus an allogeneic (donor) mini-transplant. This important study is being conducted at several of the major transplant centers in the United States. The national coordination of this and other transplant trials occurs at Froedtert & the Medical College of Wisconsin.
Q. All told, what diseases can be treated by blood or marrow transplant?Bone marrow or blood stem cell transplant can be used as a therapy for most cancers of the blood, bone marrow and lymphatic system. This includes acute and chronic leukemia, non-Hodgkin’s lymphoma, Hodgkin’s disease and multiple myeloma. It can also be used to treat some autoimmune disorders like scleroderma and multiple sclerosis, plus other inherited immune deficiencies in children, and an illness called aplastic anemia (bone marrow failure).
Q. Is blood or marrow transplant a “first choice” option or something you try only after other treatments have failed? Blood and marrow transplant is not a “last ditch” effort. Stem cell transplants are routinely used for patients with acute leukemias and for leukemia patients who are unlikely to respond well to regular chemotherapy. For other patients, we reserve transplantation until later in their disease history or after cancer has recurred.
Q. What are the outcomes for blood and marrow transplants?Survival rates vary for different diseases, and they are affected by the stage of disease and therapy before transplant. For leukemia, the cure rates range from 30 percent to 80 percent. For Hodgkin’s disease or non-Hodgkin’s lymphoma, the cure rate ranges from 40 percent to 60 percent. In certain situations like aplastic anemia, the cure rate is greater than 80 percent.
Q. You recently joined Froedtert & the Medical College of Wisconsin. What brought you here?I was attracted to our world-class Blood and Marrow Transplant Program. Many of the transplant physicians here are viewed as the best in America. In addition, our nurses, nurse practitioners and physician assistants are outstanding, and the Medical College has a world-class cell processing laboratory run by Carolyn Keever-Taylor, PhD.
The new Cancer Pavilion also provides exciting new future opportunities. This facility will allow us to increase the number of patients who can be treated or receive a transplant as an outpatient. This will shorten their time in the hospital and improve the patient’s quality of life.
Q. What are the advantages of being part of an academic medical center?For our patients, one major advantage beyond the expertise of the doctors and staff is the availability of new innovations in the field of blood and marrow transplant and oncology. These new options are not usually available when therapy is directed by community physicians.
Source: Every Day, interview with Jared Klein, MD
Date: Jan - April 2007