Acute lymphoblastic leukemia (ALL): Full guide

What is ALL?

Acute lymphoblastic leukemia (ALL) is a cancer of young white blood cells called lymphoblasts. It starts in the bone marrow. Bone marrow is the soft, spongy tissue inside your bones where blood cells are made.

Lymphoblasts normally grow into lymphocytes, the white cells that help your immune system fight infection. In ALL, these young cells grow out of control and do not mature. They crowd out healthy red cells, white cells, and platelets. ALL can also spread to the brain and spinal fluid, lymph nodes, spleen, or liver.

"Acute" means it grows fast, over days to weeks. Treatment usually starts soon after diagnosis. ALL is the most common cancer in children, but about 4 in 10 cases are in adults. This guide is about ALL in adults.

Common signs are tiredness, fevers, infections, easy bruising or bleeding, bone pain, and swollen lymph nodes. Most of the time, there is no known cause.

Adults with ALL have a lower cure rate than children. But results have improved a great deal with newer treatments, and many adults are cured. Your care team will explain the goal of your treatment.

Types

B-cell ALL

The most common type in adults, about 3 out of 4 cases. It starts in young B cells. Many newer immune treatments target proteins on these cells, called CD19 and CD22.

T-cell ALL

A type that starts in young T cells. It is more common in young men and often causes a mass in the chest. A chemotherapy drug called nelarabine is used for T-cell ALL.

Philadelphia chromosome-positive ALL (Ph+ ALL)

B-cell ALL with a swap between chromosomes 9 and 22 that makes a gene called BCR-ABL1. It is found in about 1 in 4 adults with ALL, and more often in older adults. It is treated with a daily pill called a tyrosine kinase inhibitor (TKI), which has changed its outlook.

Philadelphia chromosome-negative ALL (Ph- ALL)

ALL without the Philadelphia chromosome. It is treated with chemotherapy, and often with immune treatments such as blinatumomab.

Ph-like ALL

A higher-risk form of B-cell ALL whose genes act like Ph+ ALL, even though the Philadelphia chromosome is not there. It is more common in young adults and Hispanic people. Some people may benefit from a TKI or a clinical trial.

Early T-cell precursor ALL

A higher-risk form of T-cell ALL made of very immature cells. A stem cell transplant is often discussed.

Lymphoblastic lymphoma

The same disease as ALL, but mostly in lymph nodes or the chest, with few leukemia cells in the marrow. It is treated like ALL.

Tests you may have

Complete blood count (CBC) and blood smear

A CBC counts your white cells, red cells, and platelets. A smear lets a specialist look at your blood under a microscope. Blasts in the blood are often the first clue.

Bone marrow biopsy and aspirate

A needle takes liquid marrow and a small piece of bone, usually from the back of the hip. You get numbing medicine first. It confirms the diagnosis and gives cells for other tests.

Flow cytometry

A lab test that looks at markers on the surface of the cells. It shows whether the ALL is B-cell or T-cell, and which targets, such as CD19 and CD22, are present.

Chromosome and gene tests

Tests called karyotype, FISH, PCR, and next-generation sequencing look for changes in the leukemia cells. The most urgent result is whether the Philadelphia chromosome (BCR-ABL1) is there, because it changes your first treatment.

Lumbar puncture (spinal tap)

A thin needle takes fluid from your lower back to check for leukemia in the brain and spinal fluid. Chemotherapy is often given into the spinal fluid at the same time. You will have this many times during treatment.

Imaging scans

A CT scan may check for a mass in the chest or swollen lymph nodes. An MRI of the brain may be done if you have symptoms such as headache or weakness.

Heart test (echocardiogram)

An ultrasound of your heart. Some chemotherapy drugs can strain the heart, so your team checks it before starting.

HLA typing

A blood or cheek swab test to find a stem cell donor match. It is often done early, in case a transplant is needed. Brothers and sisters may be tested too.

MRD testing

MRD means measurable residual disease. Very sensitive tests on your marrow (and sometimes blood) can find 1 leukemia cell among 10,000 to 1,000,000 normal cells. It is checked at set times during treatment.

Risk groups and phases

ALL does not have stages like many other cancers. That is because it is already in the blood and marrow throughout the body. Instead, doctors look at risk features and at how well the leukemia responds to treatment.

Risk is based on your age, your white blood cell count at diagnosis, the gene and chromosome changes in the leukemia cells, and whether leukemia has reached the brain or spinal fluid. The most powerful sign of all is your MRD result after the first months of treatment.

Treatment for ALL is long, often 2 to 3 years in all, and is given in phases.

Standard risk

ALL with features that usually respond well, such as a younger age, a lower white count, and favorable gene changes. Becoming MRD-negative early is the best sign.

High risk

ALL with features such as older age, a very high white count, certain gene changes (such as KMT2A, low chromosome counts, or Ph-like), or MRD that is still found after treatment. A transplant may be advised.

CNS involvement

CNS means central nervous system, the brain and spinal cord. Leukemia in the spinal fluid needs extra treatment into the spinal fluid.

Induction

The first phase, about 4 to 6 weeks. The goal is to clear the leukemia and reach remission.

Consolidation and intensification

Several months of treatment after remission to kill leukemia cells that are left. Immune treatments such as blinatumomab are often given in this phase.

Maintenance

About 2 years of lower-intensity treatment, mostly daily and weekly pills with monthly checkups. It lowers the chance that ALL comes back. People with Ph+ ALL usually keep taking a TKI.

Remission

Complete remission means the marrow looks normal, blasts are under 5 out of 100 cells, and blood counts have recovered. Treatment continues, because hidden cells may remain.

Relapse

When ALL comes back after remission. It can come back in the marrow, the spinal fluid, or, in men, the testicles.

Gene and lab tests to know

ALL cells have gene changes and surface markers that guide treatment. Some results point to a targeted pill. Others show which immune treatments may work.

MRD is one of the most important tests in ALL. It shows how deeply treatment is working, helps decide if you need a transplant, and can lead to added treatment if leukemia is still found.

BCR-ABL1 (Philadelphia chromosome)

The key result in adult ALL. If it is present, a TKI pill such as imatinib, dasatinib, or ponatinib is added to treatment right away. The BCR-ABL1 level is tracked in your blood or marrow over time.

Ph-like gene changes

Changes that make B-cell ALL act like Ph+ ALL. Some, such as ABL-class changes, may respond to a TKI.

KMT2A rearrangement

A chromosome change linked to higher-risk ALL. A transplant is often considered. Newer drugs called menin inhibitors are being studied and are used for some people whose leukemia comes back.

Low chromosome count (hypodiploid)

Leukemia cells with fewer than the normal number of chromosomes. It is linked to higher risk. It may lead to testing for an inherited TP53 change.

TP53

A change linked to ALL that is harder to treat.

CD19

A protein on almost all B-cell ALL cells. Blinatumomab and CAR T-cell therapy target it.

CD22

Another protein on B-cell ALL cells. The drug inotuzumab ozogamicin targets it.

CD20

A protein on some B-cell ALL cells. The antibody rituximab may be added to chemotherapy when it is present.

MRD-negative vs MRD-positive

MRD-negative means no leukemia was found even with very sensitive tests. MRD-positive means some leukemia remains. MRD-positive ALL is often treated with blinatumomab and may lead to a transplant.

Main treatments

Chemotherapy for Ph- ALL

Treatment uses many drugs over 2 to 3 years, including steroids, vincristine, anthracyclines, asparaginase, cyclophosphamide, cytarabine, methotrexate, and mercaptopurine. Adults up to about age 40 often do best with "pediatric-inspired" plans similar to those used for children. Another common plan for adults is called hyper-CVAD.

Blinatumomab

An immune drug that links your T cells to B-cell ALL cells so the T cells can kill them. It is given as a continuous IV through a small pump you carry, usually for 4 weeks at a time. It is now added to chemotherapy for many adults with Ph- B-cell ALL, used when MRD is found, and used if ALL comes back.

Inotuzumab ozogamicin

An antibody that carries a strong chemotherapy drug directly into B-cell ALL cells that have CD22. It is used if ALL comes back, and it is being added to first treatment, especially for older adults.

TKIs for Ph+ ALL

Daily pills that block the BCR-ABL1 protein. Imatinib, dasatinib, and ponatinib are used. They are combined with steroids, with chemotherapy, or with blinatumomab. Some people can now be treated with little or no traditional chemotherapy.

CNS prophylaxis

ALL can hide in the brain and spinal fluid. To prevent this, everyone gets chemotherapy (such as methotrexate or cytarabine) injected into the spinal fluid during a spinal tap, many times during treatment. High-dose methotrexate through an IV also helps. Radiation to the brain is now rarely needed.

Treatment for T-cell ALL

T-cell ALL is treated with chemotherapy, often including nelarabine. Immune treatments that target CD19 and CD22 do not work for T-cell ALL.

Treatment for older adults

Older adults often get lower-intensity plans that use steroids, less chemotherapy, and immune drugs such as inotuzumab or blinatumomab, or a TKI for Ph+ ALL. The goal is to control the leukemia with fewer side effects.

CAR T-cell therapy

Your own T cells are collected and changed in a lab to find and kill ALL cells with CD19. They are given back once, after a short course of chemotherapy, at a specialized center. Brexucabtagene autoleucel (Tecartus) and obecabtagene autoleucel (Aucatzyl) are approved for adults whose B-cell ALL has come back or not responded. Tisagenlecleucel (Kymriah) is approved up to age 25.

Allogeneic stem cell transplant

You get strong treatment, then stem cells from a donor. The donor's immune cells can attack leukemia cells left behind. It is often advised for high-risk ALL, for MRD that is still found, or after a relapse. With better tests and drugs, fewer people in deep remission need one.

Clinical trials

Many advances in ALL came from clinical trials. Ask about trials at any stage, especially if your ALL is high risk or comes back.

Infection, transfusion, and other side effects

Infections and fever

ALL and its treatment lower your white cells, so infections are more likely. A fever can be serious and needs care right away. You will take medicines to prevent certain infections, including a type of pneumonia called PJP.

Blood and platelet transfusions

Many people need red cell and platelet transfusions, especially in the early months.

Asparaginase side effects

Asparaginase (often pegaspargase) is a key drug for ALL. It can cause allergic reactions, inflammation of the pancreas (pancreatitis), blood clots, liver problems, and high blood sugar. Your team checks your blood often. Severe belly pain needs care right away.

Steroid side effects

Prednisone and dexamethasone can raise blood sugar, cause mood changes and trouble sleeping, and increase appetite. Over time, they can weaken bones and sometimes damage the hip or knee joints (osteonecrosis). Tell your team about joint pain.

Numbness, tingling, and constipation

Vincristine can cause numbness or tingling in the hands and feet, jaw pain, and constipation. Report it early so your team can adjust the dose. Stool softeners help.

Mouth sores and kidney effects from methotrexate

High-dose methotrexate can cause mouth sores and stress the kidneys. You get lots of IV fluids and a rescue medicine called leucovorin, and your levels are checked until the drug clears.

CRS and nerve effects from blinatumomab and CAR T

These immune treatments can cause cytokine release syndrome (CRS), with fever, chills, and low blood pressure. They can also affect the nervous system, causing confusion, shaking, trouble speaking, or seizures (called ICANS). You will be watched closely, often in the hospital at first.

Liver problems from inotuzumab

Inotuzumab can cause a serious liver problem called veno-occlusive disease, where small veins in the liver get blocked. The risk is higher with a later transplant. Watch for belly swelling, fast weight gain, or yellow skin.

TKI side effects

TKIs can cause fluid buildup, rash, muscle cramps, and low blood counts. Dasatinib can cause fluid around the lungs. Ponatinib can raise blood pressure and the risk of heart problems and clots, so your team watches your heart health.

Graft-versus-host disease (GVHD)

After a donor transplant, donor immune cells can attack your skin, gut, liver, or other organs. Signs include rash, diarrhea, and yellow skin or eyes. It can be treated, and you will take medicines to prevent it.

Living with and after ALL

Treatment for ALL is long. The first months are the most intense, with hospital stays and frequent clinic visits. Maintenance is easier, and many people go back to work, school, or their usual activities during that time. Taking every dose of your maintenance pills matters.

After treatment ends, you will have regular blood tests and sometimes marrow tests. These check that the leukemia has not come back. The risk of relapse goes down the longer you stay in remission.

Some effects can show up years later. These include bone and joint problems, heart problems from anthracyclines, nerve damage, memory or thinking changes, and fertility problems. Ask your team about a survivorship care plan and which checkups you need.

Treatment can affect fertility. If you may want children, ask about saving sperm or eggs before treatment starts, if time allows. After a donor stem cell transplant, you will need your childhood vaccines again, and recovery can take a year or more.

It is normal to feel shocked, scared, or overwhelmed. Young adults may also worry about school, work, dating, and money. Social workers, counselors, and support groups can help you and your family. Blood Cancer United (formerly the Leukemia and Lymphoma Society) offers free support and information.