Adult Acute Lymphocytic Leukemia (ALL): Types and Treatment

This article gives detailed information on ALL.  You may want to read Leukemia: The Basics first, so you have a basic understanding of leukemia.

Acute lymphoid/lymphoblastic leukemia (ALL) is a blood cancer that affects your white blood cells. If your provider thinks you have ALL, you will have tests done to find out which subtype (classification) of ALL you may have. These tests may include:

• A blood smear and a bone marrow biopsy and aspiration.
• A lumbar puncture (spinal tap) to see if there are any leukemia cells in your spinal fluid.
• Flow cytometry and cytogenetic tests that look for chromosomal changes.
• Tests like CT scans of your chest, abdomen (belly), and pelvis, and an MRI of your head or spinal cord. Younger men may need a testicular ultrasound as ALL can also cause scrotal/testicular masses.

ALL is not staged like most other cancers. It is classified based on chromosomal and genetic abnormalities (changes) in the cancer cells. The classification helps your provider decide what treatment you need. ALL is classified using the World Health Organization (WHO) system. There are 3 categories: precursor B cell ALL, precursor T cell ALL, and mature B cell ALL (also called Burkitt lymphoma).

Your care team may call your leukemia by its chromosomal or genetic abnormalities. The "t" stands for translocation. The “p” and “q” tell where the abnormality is on the chromosome. These are the different classifications of ALL:

• B Lymphoblastic leukemia/lymphoma, not otherwise specified, NOS.
• B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities.
  • B lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.2), BCR-ABL1 (Philadelphia Chromosome).
  • B lymphoblastic leukemia/lymphoma with t(v;11q23); MLL rearranged.
  • B lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22) TEL-AML1.
  • B lymphoblastic leukemia/lymphoma with hyperdiploidy >50.
  • B lymphoblastic leukemia/lymphoma with hypodiploidy.
  • B lymphoblastic leukemia/lymphoma with t(5;14)(q31;q32) IL3-IGH.
  • B lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3) TCF3-PBX1.
• T Cell lymphoblastic leukemia/lymphoma.

How is ALL treated?

Treatment for ALL is based on things like your age, overall health, and test results. Your treatment may include:

• Chemotherapy.
• Targeted therapy.
• Immunotherapy.
• Stem cell transplant.

Chemotherapy, Targeted Therapy, and Immunotherapy

Chemotherapy is the main treatment for ALL and it can be complex. ALL is often treated for about 2 to 3 years and has three phases. The phases are:

•  Induction: The goal of this first phase is to get you into remission. This means as many cancer cells as possible have been destroyed through chemotherapy. In remission, your team does not see leukemia cells in your bone marrow when they look at it under a microscope. There are also no blast cells in your blood tests and your blood counts have returned to normal.
• Consolidation: This is the second phase of treatment. Sometimes it is called “intensification.” During this phase, you will get higher doses of chemotherapy than you did during induction. Medications are given in combinations and may include some of the same ones you had during induction. The goal is to kill any remaining leukemia cells and to keep you in remission.
• Maintenance: This is the third phase of treatment. The goal of maintenance is to keep you in remission. You will get lower-dose chemotherapy treatment in cycles. Maintenance therapy is not given for Burkitt's lymphoma leukemia, because it has a high cure rate with induction and consolidation therapy alone.

What chemotherapy medications you get depends on your age and the classification/sub-type of ALL you have.

The Philadelphia Chromosome is a genetic abnormality that was first found in chronic myelogenous leukemia (CML) but is also seen in more than 20 out of 100 adult ALL cases. Tyrosine Kinase Inhibitors (TKIs) are a type of targeted therapy used in the treatment of Ph+ ALL. They include imatinib, ponatinib, nilotinib, bosutinib, and dasatinib. These medications are used alone or with other medications such as cyclophosphamide, vincristine, daunorubicin, dexamethasone, cytarabine, methotrexate, pegaspargase, etoposide, blinatumomab, and prednisone.

Ph- ALL also uses a combination of medications for induction. These include nelarabine, pegaspargase, cytarabine,cyclophosphamide, methotrexate, l-asparaginase, and rituximab. In patients with relapsed or refractory Ph-negative ALL, chemotherapy medications could include those listed above as well as blinatumomab, inotuzumab ozogamicin, clofarabine, fludarabine, idarubicin, etoposide and mitoxantrone.

Tisagenlecleucel is a CAR-T immunotherapy that may be used in the treatment of both Ph+ and Ph- refractory ALL. In this treatment, the patient’s own immune cells are used to treat their cancer.

Consolidation therapy uses some similar medications, but the schedule can be different, based on your subtype of ALL. Consolidation is given over a period of 4 to 8 months. If you are a candidate for stem cell transplant, the transplant would likely be done in place of consolidation and maintenance therapy.

Maintenance therapy consists of mercaptopurine (6-MP), methotrexate, vincristine, and prednisone, given over 2 to 3 years. Studies found no benefit to increasing this time but did find outcomes to be worse if the maintenance period was shorter.

Measurable or Minimal Residual Disease Testing

Measurable or minimal residual disease (MRD) testing is used to see if the cancer treatment is working and to guide further treatment plans. MRD tests use highly sensitive methods to look for any remaining cancer cells that may not be seen in routine tests. MRD testing should be done in adults with ALL after they have induction chemotherapy. Your team may want you to have this test again at other times during treatment.

Central Nervous System (CNS) Prophylaxis

Less than 10 out of 100 patients have CNS involvement of leukemia (leukemia found in the spinal fluid) at the time of diagnosis. But, 50 to 75 out of 100 patients will have this by 1 year if they don’t have preventive therapy. The most effective therapy to prevent CNS disease in adults with ALL is intrathecal chemotherapy. This means that chemotherapy is given directly into the spinal canal. This can be done by a lumbar puncture (spinal tap), or through a catheter called an Ommaya reservoir that is surgically placed in the head. This catheter allows you to have many intrathecal infusions without needing many lumbar punctures. The number of intrathecal infusions given depends on the subtype of ALL and the risk of CNS disease that subtype has.

Stem Cell Transplant

The use of stem cell transplant for ALL is not completely clear. It is often used early in therapy for patients with high-risk ALL subtypes in their first remission. Current clinical trials are looking at the best time for transplant (first or second remission, before maintenance therapy, etc.) and trying to figure out which patients will benefit most from transplant.

Complications & Concerns of Leukemia and Treatment

Leukemia puts you at a higher risk of infection (because your white blood cell count is low) and bleeding (because your platelet count is low). Treatment of leukemia should help your abnormal blood counts, but your counts may get worse before they get better. You will likely get blood and platelet transfusions, and antibiotics, and will need to be extra careful to avoid infection or bleeding.

Hand washing is the best way to prevent infection. You and your visitors should wash your hands often. You may not be able to eat some types of fresh fruit and vegetables or get fresh flowers or plants while in the hospital. (See the gift guide for ideas on what to send a patient with these restrictions). This may sound odd, but these items can bring in bacteria and may put you at a higher risk of infection. Ask any sick family members to hold off on visiting until they feel better.

You may get an infection or fever. If this happens, you will have some tests done to look for where the infection is in your body. These tests can include blood, urine, and stool cultures, and a chest x-ray. Antibiotics may be started or adjusted if they are already being given.

During your treatment, you may need blood (for low hemoglobin levels) or platelet (for low platelet counts) transfusions. If you have a low hemoglobin count (also called anemia), you may feel fatigued, short of breath, or look pale. A low platelet count (also called thrombocytopenia) can lead to bleeding. This can be as small as gums bleeding when brushing the teeth or a nosebleed, or dangerous bleeding, like a stroke. Be careful and try to avoid bumping into things. Don’t shave with a razor (an electric razor is okay to use with caution) and avoid any activities that increase the risk of bleeding or bruising. Patients should always tell their healthcare team if they have symptoms of anemia or thrombocytopenia.

Clinical Trials

You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Service.

Making Treatment Decisions

Your care team will make sure you are a part of choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. Friends and family can help you talk through the options and the pros and cons of each, but they cannot decide for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.