What’s New in Acute Lymphocytic Leukemia (ALL) Research?

Researchers are now studying the causes, genetics, and treatment of acute lymphocytic leukemia (ALL) at many medical centers, universities, and other institutions around the world.

Research into the genetics of ALL

Scientists are learning a lot about how DNA (gene) changes inside normal bone marrow cells can cause them to develop into leukemia cells, including ALL cells. They now understand more about the gene changes that often happen in ALL cells. This has given them greater insight into why these cells become abnormal.

As researchers find more of these changes, it is becoming clear that there are many types of ALL.

How this informs treatment

Each type of ALL has different gene changes that affect how the leukemia might progress and which treatments might be most helpful. Doctors are now learning how to use these changes to help determine a person’s outlook and whether they should get more, or less, intensive treatment.

Perhaps even more important, this knowledge is now helping researchers develop newer targeted therapy and immunotherapy drugs against ALL.

For example:

• Targeted drugs called tyrosine kinase inhibitors (TKIs) are now used to help treat people with ALL whose leukemia cells have the Philadelphia chromosome.
• Many other drugs targeting changes in ALL cells are now being developed as well.

Newer lab techniques to help classify ALL

Newer lab techniques are now helping researchers identify and classify different types of ALL. Instead of looking at single genes, these tests can look at the patterns of many different genes in the cancer cells at the same time. This may add to the information that comes from current lab tests.

This information may eventually allow for more personalized treatment of ALL.

Finding minimal residual disease

Very sensitive tests can now detect even the smallest amount of leukemia left after treatment (known as minimal residual disease, measurable residual disease, or MRD).

These tests can detect disease even when there are so few leukemia cells left that they can’t be found by routine bone marrow tests. For example:

• The polymerase chain reaction (PCR) test can identify even very small numbers of ALL cells in a sample based on their gene changes.
• A PCR test can be useful in determining how completely the treatment has destroyed the ALL cells.

Doctors are now trying to determine what effect MRD has on a person’s outlook and how this might affect the need for further or more intensive treatment.

Improving treatment for ALL

Treatment for ALL can be very effective for some people. But it doesn't cure everyone (especially adults), and it can often cause serious or even life-threatening side effects.

Many studies are trying to find more effective and safer treatments for ALL.

Chemotherapy

Chemotherapy (chemo) is still the main treatment for nearly all people with ALL. Studies are now looking for the most effective combination of chemo drugs while limiting unwanted side effects. This is especially important in older people, who often have a harder time tolerating current treatments.

New chemo drugs are also being developed and tested.

Studies are also underway to determine whether people with certain prognostic factors might benefit from more intensive chemo and whether some people with ALL might not need as much treatment.

Stem cell transplants

Researchers continue to refine stem cell transplants to try to increase their effectiveness, reduce complications, and determine which people are most likely to be helped by this type of treatment. Many studies are trying to figure out exactly when different types of transplants might best be used.

Doctors are also studying donor leukocyte infusion (DLI) in people who relapse after getting an allogeneic transplant.

For a DLI, a person gets an infusion of white blood cells (leukocytes) from the same donor who gave stem cells for the original transplant. The hope is that the cells will boost the new immune system and add to the graft-versus-leukemia effect.

Targeted therapy drugs

Newer targeted drugs that specifically attack some of the gene changes seen in ALL cells are now becoming an important part of treatment for some people with ALL. These drugs work differently from standard chemotherapy drugs.

Immunotherapy

The goal of immunotherapy is to boost the body’s immune system to help fight off or destroy cancer cells. Several types of immunotherapy are now used to treat ALL, and others are being studied.

T cell engagers (TCEs)

TCEs are monoclonal antibodies (manmade immune system proteins) that can attach to 2 different proteins on cells in the body at the same time.

They can be designed so one part attaches to a protein on ALL cells, while the other part attaches to a protein on immune cells called T cells. By binding to both proteins, this drug brings the leukemia cells and immune cells together, which helps the immune system attack the leukemia cells.

Antibody-drug conjugates (ADCs)

ADCs are monoclonal antibodies attached to a chemo drug. Once in the body, the antibody acts as a homing device to bring the chemo drug to the leukemia cells, where it enters the cells and kills them when they try to divide into new cells.

CAR T-cell therapy

CAR T-cell therapy is a promising new way to get the immune system to fight leukemia. Immune cells called T cells are removed from a person’s blood and altered in the lab so they have specific substances (called chimeric antigen receptors, or CARs) that help them attach to leukemia cells.

The CAR T cells are then grown in the lab and infused back into the person’s blood, where they can seek out the leukemia cells and attack them.