A Gentler Option for Leukemia: Reduced-Intensity BMT

Leukemia is a type of blood cancer that begins when bone marrow produces abnormal white blood cells. The abnormal cells lose the ability to fight infection, which is their main function. They also interfere with the production of red cells, which carry oxygen to tissue, and platelets, which help control bleeding.

The National Cancer Institute estimates that 44,270 new cases of leukemia will be diagnosed this year, and 21,710 people will die from the disease.

Acute vs Chronic Leukemia
Leukemia can be either acute or chronic.

In acute leukemia, the affected white blood cells are very abnormal and can increase rapidly. Acute leukemia typically worsens quickly.

In chronic leukemia, the abnormal blood cells still work, and people with chronic leukemia might not show any symptoms. Chronic leukemia generally gets worse slowly. Eventually, symptoms begin as more leukemia cells form in the bone marrow, preventing production of normal cells.

Types of Leukemia
Leukemia is grouped by the type of white blood cell that is affected. It can start in myeloid cells or lymphoid cells. There are four common types of leukemia:

  • Acute myeloid leukemia (also called acute myelogenous leukemia or AML) accounts for about 10,600 new cases of leukemia each year.
  • Acute lymphocytic leukemia (also called acute lymphoblastic leukemia or ALL) accounts for about 3,800 new cases of leukemia each year.
  • Chronic myeloid leukemia (also called chronic myelogenous leukemia or CML) accounts for about 4,400 new cases of leukemia each year.
  • Chronic lymphocytic leukemia (also called chronic lymphoblastic leukemia or CLL) accounts for about 7,000 new cases of leukemia each year. Most often, people diagnosed with the disease are over age 55.

Of the four leukemia types, AML, CML and CLL are more common in the elderly. ALL is the most common type of leukemia in young children, but it is also seen in adults.

New Transplantation Techniques
Christopher N. Bredeson, MD, MSc, FRCPC, is a Medical College of Wisconsin Associate Professor of Medicine (Neoplastic Diseases, Bone Marrow Transplant) and Director of Hematological Malignancies. He practices at the Froedtert & Medical College Neoplastic Diseases and Related Disorders clinic.

In previous issues of HealthLink, Dr. Bredeson discussed types of leukemia and the remarkable progress of researchers in finding new treatments both for children and adult patients. Here, he describes advances in bone marrow transplant techniques that have allowed more people to take advantage of this life-saving treatment.

The Traditional Transplantation Process
Before patients can receive healthy bone marrow by transplantation, they need high doses of chemotherapy and often radiation to destroy their own abnormal blood cells and to suppress their immune system. Without this procedure, the immune system will react to new bone marrow just as it does to any substance it considers ‘foreign’ – it will try to reject it.

After the patient’s abnormal bone marrow has been destroyed and immune system suppressed, it is replaced with healthy marrow – either the patient’s own undamaged marrow (called an autologous transplant), marrow donated by someone else (an allogeneic transplant), or donated by an identical twin (a syngeneic transplant).

In the operating room, bone marrow is removed from the donor’s hip bone while he or she is under anesthesia. The marrow is filtered, treated, and either transplanted immediately or frozen and stored for later use. The healthy marrow is transfused into the patient.

These same cells can be collected from the donor’s circulating blood after several days of a medication that stimulates the bone marrow to release them into the circulation. The process of collecting the cells from the circulation is called apheresis. During apheresis the donor is connected to a machine that skims off the cells we want for transplant and returns the rest to the donor.

After giving the donated cells to the patient, it takes about 10 to 20 days for the bone marrow to settle in. During this time, the patient needs blood cell transfusions and other supportive care while waiting for the transplanted cells to replace the old bone marrow and restore production of blood cells.

Older Patients, Newer Treatments
Older patients often have more trouble handling medical procedures in general; those who are already weakened by illness can be at increased risk for complications. “The problem with some of these diseases and in some circumstances is still that the only curative therapy is to have a bone marrow transplant. But as patients get older, many of them can’t tolerate a transplant,” Dr. Bredeson says.

“The trick is to get the cells into the patient. You’re relying on donor cells to make a new immune system, and relying on that immune system to fight off and kill off the malignancy or leukemia.” Unfortunately, the chemotherapy or radiation required before transplantation can damage healthy tissue along with the cells they are meant to kill.

But that’s starting to change, says Dr. Bredeson. Some of the newer chemotherapy drugs cause less tissue damage but still do a good job of suppressing the immune system. Combined with low doses of radiation, this can be enough to allow donor cells to grow.

“This is a big advance in treatment of hematological malignancies,” Dr. Bredeson explains. “It used to be that the upper limit was 50 to 55 years of age for a person to have a transplant from a donor, yet the majority of people who have the diseases are older than that. Now we can do transplants in patients into their mid 60s. Not in every patient – they still need to be reasonably healthy – but reduced-intensity transplantation has become a potential cure for many patients who otherwise didn’t have that option.”

Dr. Bredeson and his colleagues have taken part in research needed to advance the new treatment techniques. “We’re involved with a lot of work in different consortiums and we’ve participated in several transplant trials in elderly patients with these diseases,” he notes.

“With the newer agents and transplant approaches, there are people who are having their lives extended, and people who are potentially cured, that we couldn’t have treated nearly so effectively even five years ago.”

“Caring for people with some types of leukemia used to be very discouraging, and very hard on the caregivers. Now, with these newer approaches, there is a lot of excitement that we can improve patients’ disease control, and if we do that then they don’t need transfusions as often, they don’t need to be in clinic all the time, and potentially they can live longer.” Dr. Bredeson says.

“The standard approaches to acute leukemia haven’t improved very much, but these newer agents are really changing the way we think about some of these diseases and inspiring new strategies that we didn’t have before.”

“These are still terrible diseases, but now they can often be kept under control, and in many cases cured.”

This article includes information from the National Cancer Institute.