In people with leukemia, the bone marrow produces too many white blood cells, many of them abnormal. These abnormal cells not only lose their infection-fighting ability, they also interfere with the production of red cells and platelets.

Christopher N. Bredeson, MD, MSc, FRCPC, is 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 Newer Therapies Make Inroads Against Adult Leukemias, Dr. Bredeson described recent advances in the treatment of three types of leukemia that affect adults. Here, he discusses the remarkable progress of leukemia research.

Dr. Bredeson explains that although the precise causes of leukemia are unknown, a genetic component of the disease has been fairly well established. "Sometimes what happens in the process is that one of the very early cells becomes abnormal, usually because the chromosomes or the genetic material inside the cell becomes confused or mixed up," he says. "When that happens, the cell no longer listens to messages from the body about when to grow and divide and mature. The cell ends up just making copies of itself. These immature cells are called blasts.

"The bone marrow is really just like a factory, and if you fill a factory up with junk it can't make the product that it should be making - in this case good, properly functioning cells. When the marrow is crowded out with these junky blast cells, you run out of the good elements.

"If you don't have infection-fighting cells than you'll present with fever, pneumonia, sinus infection and those types of things. When you don't have enough red blood cells you don't have enough oxygen being carried around to the body and you feel weak and have low energy. If you don't have platelets then you're at risk for bruising and bleeding, and that bleeding often presents as nosebleeds or gum bleeding."

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

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

In chronic leukemia, the abnormal blood cells can still do their work, and people with chronic leukemia may not have any symptoms for a long time. Slowly, chronic leukemia gets worse. It causes symptoms as the number of leukemia cells in the blood rises and the bone marrow becomes crowded, again preventing production of the normal blood elements.

"With acute leukemia people usually go from feeling well to being unwell within a couple of weeks and show up with some complaint that's then investigated. If you have a lot of bone marrow activity and the marrow is full of these bad cells, you can actually have bone pain or aching or low-grade fever that isn't from infection but from the pressure inside of the bone marrow or the rapid growing of the blasts," Dr. Bredeson says.

"The chronic leukemias are a little bit different. They're called chronic because you can have them for a long time either with or without treatment, whereas in acute leukemia if nothing is done you will succumb to the illness in a short period of time. The chronic leukemias are more commonly detected by chance, for example through a blood test prior to an unrelated surgery."

Types of Leukemia
Leukemia is grouped by the type of white blood cell that is affected. Leukemia can arise in lymphoid cells or myeloid cells. Leukemia that affects lymphoid cells is called lymphocytic leukemia. Leukemia that affects myeloid cells is called myeloid leukemia or myelogenous leukemia.

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 in adults.
• Acute lymphocytic leukemia (also called acute lymphoblastic leukemia or ALL) accounts for about 3,800 new cases of leukemia each year. It is the most common type of leukemia in young children, but it also affects adults.
• Chronic myeloid leukemia (also called chronic myelogenous leukemia or CML) accounts for about 4,400 new cases of leukemia each year. It affects mainly adults.
• 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. It almost never affects children.

Of the four types, AML, CML, and CLL, are more common in the elderly. ALL is seen both in children and adults, but more commonly in children.

Advances in Pediatric Research
In acute lymphocytic leukemia (ALL), lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This can lead to repeated infections, anemia, and easy bleeding.

This type of leukemia, the most common cancer in children, usually gets worse quickly if it is not treated.

"Pediatric ALL (acute lymphocytic leukemia) had terrible survivorship 30 years ago," says Dr. Bredeson. "Today, that has changed dramatically."

"Pediatric hematologists and transplant specialists working together over the years to manage the pediatric diseases have made great strides. The biology of the disease is different in children than it is in adults. Leukemia in older patients is probably inherently more resistant to treatment, combined with the fact that older patients can't tolerate as much toxicity as younger patients can. Those two things together are the key factors in the difference in treatment outcomes between children and adults.

"Pediatric leukemia doctors over the past 30 years have made a lot more progress than adult leukemia doctors in addressing the diseases. Now more than 80% of kids with ALL can be cured with standard approaches, so for ALL, the more typical leukemia in children, transplant is less commonly used or required. This success results from decades of cooperative effort and studies by pediatric hematologists across the country."

Now researchers have stepped up the development of more targeted therapies for adults. "The population is aging, so there are more people around us who have these diseases," says Dr. Bredeson. The situation makes it increasingly important to generate therapies for adults.

"Leukemia is easier to study than liver cancer or lung cancer, for example, because we can more easily get samples of the tissue that's involved (bone marrow or blood) than some of the other tissues. The relative ease of studying leukemia is a big reason a lot more progress has been made in treating it. There's been a lot of development of therapies in the last five years, and I believe that progress in figuring out how to best use them will move along quickly in the next five."

In an upcoming issue of HealthLink, Dr. Bredeson will discuss recent advances in the treatment of adult leukemias.