Leukemia, Acute Lymphoblastic (ALL)

  • Dana-Farber/Brigham and Women's Cancer Care

    Acute lymphoblastic leukemia (ALL) is a fast-growing type of leukemia in which too many immature white blood cells are found in the blood and bone marrow. Learn about acute lymphoblastic leukemia and find information on how we support and care for people with ALL before, during, and after treatment.

Treatment

Your fight against acute lymphoblastic leukemia (ALL) calls for care that is both knowledgeable and compassionate. Our Adult Leukemia Program includes a team of knowledgeable, compassionate specialists who aren't just experts in treating cancer; they are global leaders in treating leukemia — and in treating your type of leukemia, in particular.

Exceptional Care for Patients with Acute Lymphoblastic Leukemia

  • World-class care from a full array of specialists — including medical and radiation oncologists, infectious disease specialists, nursing professionals, physician assistants, psychologists, and social workers — with years of expertise in caring for patients with ALL.
  • Development of the personalized treatment plan that's best for you — with options ranging from standard supportive care to intensive chemotherapy, as needed.
  • Access to both conventional and innovative treatments, including bone marrow/stem cell transplantation, combination chemotherapy, radiation therapy, and immune-based therapies and vaccines.
  • Close collaboration with you and your family as key members of the treatment team.
  • Partnership with your referring physician at each stage of your treatment, including follow-up care that's closer to your home.
  • Comprehensive support services for you and your family, including patient and caregiver education and survivorship programs to help you live well beyond cancer.
  • The full expertise of two renowned medical centers: Brigham and Women's Hospital and Dana-Farber Cancer Institute.

Contact us

To schedule a consultation or request a second opinion from our multidisciplinary team, please contact us at 617-632-6028 or 617-632-5138 or fill out our secure online form.

Information for: Patients | Healthcare Professionals

General Information About Adult Acute Lymphoblastic Leukemia

Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).

Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated.

Anatomy of the bone; drawing shows spongy bone, red marrow, and yellow marrow. A cross section of the bone shows compact bone and blood vessels in the bone marrow. Also shown are red blood cells, white blood cells, platelets, and a blood stem cell.  
Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the center of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.

Leukemia may affect red blood cells, white blood cells, and platelets.

Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.

A myeloid stem cell becomes one of three types of mature blood cells:

  • Red blood cells that carry oxygen and other substances to all tissues of the body.
  • Platelets that form blood clots to stop bleeding.
  • Granulocytes (white blood cells) that fight infection and disease.

A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):

  • B lymphocytes that make antibodies to help fight infection.
  • T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
  • Natural killer cells that attack cancer cells and viruses.
Blood cell development; drawing shows the steps a blood stem cell goes through to become a red blood cell, platelet, or white blood cell. A myeloid stem cell becomes a red blood cell, a platelet, or a myeloblast, which then becomes a granulocyte (the types of granulocytes are eosinophils, basophils, and neutrophils). A lymphoid stem cell becomes a lymphoblast and then becomes a B-lymphocyte, T-lymphocyte, or natural killer cell.  
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

In ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells are also called leukemia cells. These leukemia cells are not able to fight infection very well. Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may cause infection, anemia, and easy bleeding. The cancer can also spread to the central nervous system (brain and spinal cord).

This summary is about adult acute lymphoblastic leukemia. See the following PDQ summaries for information about other types of leukemia:

  • Childhood Acute Lymphoblastic Leukemia Treatment.
  • Adult Acute Myeloid Leukemia Treatment.
  • Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment.
  • Chronic Lymphocytic Leukemia Treatment.
  • Chronic Myelogenous Leukemia Treatment.
  • Hairy Cell Leukemia Treatment.

Previous chemotherapy and exposure to radiation may increase the risk of developing ALL.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Possible risk factors for ALL include the following:

  • Being male.
  • Being white.
  • Being older than 70.
  • Past treatment with chemotherapy or radiation therapy.
  • Being exposed to radiation from an atomic bomb.
  • Having certain geneticdisorders, such as Down syndrome.

Signs and symptoms of adult ALL include fever, feeling tired, and easy bruising or bleeding.

The early signs and symptoms of ALL may be like the flu or other common diseases. Check with your doctor if you have any of the following:

  • Weakness or feeling tired.
  • Fever or night sweats.
  • Easy bruising or bleeding.
  • Petechiae (flat, pinpoint spots under the skin, caused by bleeding).
  • Shortness of breath.
  • Weight loss or loss of appetite.
  • Pain in the bones or stomach.
  • Pain or feeling of fullness below the ribs.
  • Painless lumps in the neck, underarm, stomach, or groin.
  • Having many infections.

These and other signs and symptoms may be caused by adult acute lymphoblastic leukemia or by other conditions.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose adult ALL.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as infection or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
  • Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells and platelets.
    • The number and type of white blood cells.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.
    Complete blood count (CBC); left panel shows blood being drawn from a vein on the inside of the elbow using a tube attached to a syringe; right panel shows a laboratory test tube with blood cells separated into layers: plasma, white blood cells, platelets, and red blood cells.  
    Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Peripheral blood smear: A procedure in which a sample of blood is checked for blast cells, the number and kinds of white blood cells, the number of platelets, and changes in the shape of blood cells.
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.
    Bone marrow aspiration and biopsy; drawing shows a patient lying face down on a table and a Jamshidi needle (a long, hollow needle) being inserted into the hip bone. Inset shows the Jamshidi needle being inserted through the skin into the bone marrow of the hip bone. 
    Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.

    The following tests may be done on the samples of blood or bone marrow tissue that are removed:

    • Cytogeneticanalysis: A laboratory test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if there are certain changes in the chromosomes in the lymphocytes. For example, sometimes in ALL, part of one chromosome is moved to another chromosome. This is called the Philadelphia chromosome. Other tests, such as fluorescence in situ hybridization (FISH), may also be done to look for certain changes in the chromosomes.
      Philadelphia chromosome; three-panel drawing shows a piece of chromosome 9 and a piece of chromosome 22 breaking off and trading places, creating a changed chromosome 22 called the Philadelphia chromosome. In the left panel, the drawing shows a normal chromosome 9 with the abl gene and a normal chromosome 22 with the bcr gene. In the center panel, the drawing shows chromosome 9 breaking apart in the abl gene and chromosome 22 breaking apart below the bcr gene. In the right panel, the drawing shows chromosome 9 with the piece from chromosome 22 attached and chromosome 22 with the piece from chromosome 9 containing part of the abl gene attached. The changed chromosome 22 with bcr-abl gene is called the Philadelphia chromosome. 
      Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.
    • Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose the subtype of ALL by comparing the cancer cells to normal cells of the immune system. For example, a cytochemistry study may test the cells in a sample of tissue using chemicals (dyes) to look for certain changes in the sample. A chemical may cause a color change in one type of leukemia cell but not in another type of leukemia cell.
     

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The age of the patient.
  • Whether the cancer has spread to the brain or spinal cord.
  • Whether there are certain changes in the genes, including the Philadelphia chromosome.
  • Whether the cancer has been treated before or has recurred (come back).

Stages of Adult Acute Lymphoblastic Leukemia

Once adult ALL has been diagnosed, tests are done to find out if the cancer has spread to the central nervous system (brain and spinal cord) or to other parts of the body.

The extent or spread of cancer is usually described as stages. It is important to know whether the leukemia has spread outside the blood and bone marrow in order to plan treatment. The following tests and procedures may be used to determine if the leukemia has spread:

  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
    Lumbar puncture; drawing shows a patient lying in a curled position on a table and a spinal needle (a long, thin needle) being inserted into the lower back. Inset shows a close-up of the spinal needle inserted into the cerebrospinal fluid (CSF) in the lower part of the spinal column. 
    Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of the abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

There is no standard staging system for adult ALL.

The disease is described as untreated, in remission, or recurrent.

Untreated adult ALL  

The ALL is newly diagnosed and has not been treated except to relieve signs and symptoms such as fever, bleeding, or pain.

  • The complete blood count is abnormal.
  • More than 5% of the cells in the bone marrow are blasts (leukemia cells).
  • There are signs and symptoms of leukemia.

Adult ALL in remission  

The ALL has been treated.

  • The complete blood count is normal.
  • 5% or fewer of the cells in the bone marrow are blasts (leukemia cells).
  • There are no signs or symptoms of leukemia other than in the bone marrow.

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent adult acute lymphoblastic leukemia (ALL) is cancer that has recurred (come back) after going into remission. The ALL may come back in the blood, bone marrow, or other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with adult ALL.

Different types of treatment are available for patients with adult acute lymphoblastic leukemia (ALL). Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

The treatment of adult ALL usually has two phases.

The treatment of adult ALL is done in phases:

  • Remission induction therapy: This is the first phase of treatment. The goal is to kill the leukemiacells in the blood and bone marrow. This puts the leukemia into remission.
  • Post-remission therapy: This is the second phase of treatment. It begins once the leukemia is in remission. The goal of post-remission therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse. This phase is also called remission continuation therapy.

Treatment called central nervous system (CNS) sanctuary therapy is usually given during each phase of therapy. Because standard doses of chemotherapy may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to "find sanctuary" (hide) in the CNS. High doses of certain anticancer drugs, intrathecal chemotherapy, and radiation therapy to the brain are able to reach leukemia cells in the CNS. They are given to kill the leukemia cells and keep the cancer from recurring (coming back). CNS sanctuary therapy is also called CNS prophylaxis.

Four types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Intrathecal chemotherapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used to prevent cancer from spreading to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein.

Intrathecal chemotherapy; drawing shows the cerebrospinal fluid (CSF) in the brain and spinal cord, and an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). Top section shows a syringe and needle injecting anticancer drugs into the Ommaya reservoir. Bottom section shows a syringe and needle injecting anticancer drugs directly into the cerebrospinal fluid in the lower part of the spinal column. 
Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.

 

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. External radiation therapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.

Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

Stem Cell Transplant

Drawing of stem cells being removed from a patient or donor. Blood is collected from a vein in the arm and flows through a machine that removes the stem cells; the remaining blood is returned to a vein in the other arm.   Drawing of a health care provider giving a patient treatment to kill blood-forming cells. Chemotherapy is given to the patient through a catheter in the chest.   Drawing of stem cells being given to the patient through a catheter in the chest.  

Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.

Stem cell transplant (Step 2). The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).

Stem cell transplant (Step 3). The patient receives stem cells through a catheter placed into a blood vessel in the chest.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Targeted therapy drugs called tyrosine kinase inhibitors are used to treat some types of adult ALL. These drugs block the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (blasts) than the body needs. Three of the drugs used are imatinib mesylate (Gleevec), dasatinib, and nilotinib.

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Patients with ALL may have late effects after treatment.

Side effects from cancer treatment that begin during or after treatment and continue for months or years are called late effects. Late effects of treatment for ALL may include the risk of second cancers (new types of cancer). Regular follow-up exams are very important for long-term survivors.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Adult Acute Lymphoblastic Leukemia

Untreated Adult Acute Lymphoblastic Leukemia

Standard treatment of adult acute lymphoblastic leukemia (ALL) during the remission induction phase includes the following:

  • Combination chemotherapy.
  • Tyrosine kinase inhibitortherapy with imatinib mesylate, in certain patients. Some of these patients will also have combination chemotherapy.
  • Supportive care including antibiotics and red blood cell and platelettransfusions.
  • CNS prophylaxis therapy including chemotherapy (intrathecal and/or systemic) with or without radiation therapy to the brain.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated adult acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Adult Acute Lymphoblastic Leukemia in Remission

Standard treatment of adult ALL during the post-remission phase includes the following:

  • Chemotherapy.
  • Tyrosine kinase inhibitortherapy.
  • Chemotherapy with stem cell transplant.
  • CNS prophylaxis therapy including chemotherapy (intrathecal and/or systemic) with or without radiation therapy to the brain.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult acute lymphoblastic leukemia in remission. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Recurrent Adult Acute Lymphoblastic Leukemia

Standard treatment of recurrent adult ALL may include the following:

  • Combination chemotherapy followed by stem cell transplant.
  • Low-doseradiation therapy as palliative care to relieve symptoms and improve the quality of life.
  • Tyrosine kinase inhibitortherapy with dasatinib for certain patients.

Some of the treatments being studied in clinical trials for recurrent adult ALL include the following:

  • A clinical trial of stem cell transplant using the patient's stem cells.
  • A clinical trial of biologic therapy.
  • A clinical trial of new anticancer drugs.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Adult Acute Lymphoblastic Leukemia

For more information from the National Cancer Institute about adult acute lymphoblastic leukemia, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on June 6, 2014.


General Information About Adult Acute Lymphoblastic Leukemia (ALL)

ALL (also called acute lymphocytic leukemia) is an aggressive type of leukemia characterized by the presence of too many lymphoblasts or lymphocytes in the bone marrow and peripheral blood. It can spread to the lymph nodes, spleen, liver, central nervous system (CNS), and other organs. Without treatment, ALL usually progresses quickly.

Signs and symptoms of ALL may include the following:

  • Weakness or fatigue.
  • Fever or night sweats.
  • Bruises or bleeds easily (i.e., bleeding gums, purplish patches in the skin, or petechiae [flat, pinpoint spots under the skin]).
  • Shortness of breath.
  • Unexpected weight loss or anorexia.
  • Pain in the bones or joints.
  • Swollen lymph nodes, particularly lymph nodes in the neck, armpit, or groin, which are usually painless.
  • Swelling or discomfort in the abdomen.
  • Frequent infections.

ALL occurs in both children and adults. It is the most common type of cancer in children, and treatment results in a good chance for a cure. For adults, the prognosis is not as optimistic. This summary discusses ALL in adults. (Refer to the PDQ summary on Childhood Acute Lymphoblastic Leukemia Treatment for more information about ALL in children.)

Incidence and Mortality

Estimated new cases and deaths from ALL in the United States in 2014:[1]

  • New cases: 6,020.
    • Children (aged 0–14 years) cases: 2,670 (26% of common cancers in children).
    • Adolescents (aged 15–19 years) cases: 410 (8% of common cancers in adolescents).
  • Deaths: 1,440.

Anatomy

ALL presumably arises from malignant transformation of B- or T-cell progenitor cells.[2] It is more commonly seen in children, but can occur at any age. The disease is characterized by the accumulation of lymphoblasts in the marrow or in various extramedullary sites, frequently accompanied by suppression of normal hematopoiesis. B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective lineage developments. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface along, with nuclear terminal deoxynucleotide transferase (TdT), while precursor T-cell ALL cells commonly express CD2, CD3, CD7, CD34, and TdT.

Blood cell development; drawing shows the steps a blood stem cell goes through to become a red blood cell, platelet, or white blood cell. A myeloid stem cell becomes a red blood cell, a platelet, or a myeloblast, which then becomes a granulocyte (the types of granulocytes are eosinophils, basophils, and neutrophils). A lymphoid stem cell becomes a lymphoblast and then becomes a B-lymphocyte, T-lymphocyte, or natural killer cell.
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

Molecular Genetics

It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is cytogenetically indistinguishable from the Philadelphia chromosome (Ph1).[3] The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of adults and a small percentage of children with ALL.[4] In the majority of children and in more than one-half of adults with Ph1-positive ALL, the molecular abnormality is different from that in Ph1-positive chronic myelogenous leukemia (CML).

Many patients who have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics. The bcr-abl fusion gene may be detectable only by fluorescence in situ hybridization (FISH) or reverse-transcriptase polymerase chain reaction (RT-PCR) because many patients have a different fusion protein from the one found in CML (p190 vs. p210). These tests should be performed, whenever possible, in patients with ALL, especially in those with B-cell lineage disease.

L3 ALL is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).

Diagnosis

Patients with ALL may present with a variety of hematologic derangements ranging from pancytopenia to hyperleukocytosis. In addition to a history and physical, the initial workup should include:

  • Complete blood count with differential.
  • A chemistry panel (including uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, and hepatic transaminases).
  • Fibrinogen and tests of coagulation as a screen for disseminated intravascular coagulation.
  • A careful screen for evidence of active infection.

A bone marrow biopsy and aspirate are routinely performed even in T-cell ALL to determine the extent of marrow involvement. Malignant cells should be sent for conventional cytogenetic studies, as detection of the Ph1 t(9;22), myc gene rearrangements (in Burkitt leukemia), and MLL gene rearrangements add important prognostic information. Flow cytometry should be performed to characterize expression of lineage-defining antigens and allow determination of the specific ALL subtype. In addition, for B-cell disease, the malignant cells should be analyzed using RT-PCR and FISH for evidence of the bcr-abl fusion gene. This last point is of utmost importance, as timely diagnosis of Ph1 ALL will significantly change the therapeutic approach.

Diagnostic confusion with AML, hairy cell leukemia, and malignant lymphoma is not uncommon. Proper diagnosis is crucial because of the difference in prognosis and treatment of ALL and AML. Immunophenotypic analysis is essential because leukemias that do not express myeloperoxidase include M0 AML, M7 AML, and ALL.

The examination of bone marrow aspirates and/or biopsy specimens should be done by an experienced oncologist, hematologist, hematopathologist, or general pathologist who is capable of interpreting conventional and specially stained specimens.

Prognosis and Survival

Factors associated with prognosis in patients with ALL include the following:

  • Age: Age, which is a significant factor in childhood ALL and AML, may be an important prognostic factor in adult ALL. In one study, overall, the prognosis was better in patients younger than 25 years; another study found a better prognosis in patients younger than 35 years. These findings may, in part, be related to the increased incidence of the Ph1 in older ALL patients, a subgroup associated with poor prognosis.[5][6]
  • CNS involvement: As in childhood ALL, adult patients with ALL are at risk of developing CNS involvement during the course of their disease. This is particularly true for patients with L3 (Burkitt) morphology.[7] Both treatment and prognosis are influenced by this complication.
  • Cellular morphology: Patients with L3 morphology showed improved outcomes, as evidenced in a completed Cancer and Leukemia Group B study (CLB-9251 [NCT00002494]), when treated according to specific treatment algorithms.[8][9] This study found that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like chemotherapy regimens.[8][10][11]
  • Chromosomal abnormalities: Chromosomal abnormalities, including aneuploidy and translocations, have been described and may correlate with prognosis.[12] In particular, patients with Ph1-positive t(9;22) ALL have a poor prognosis and represent more than 30% of adult cases. Bcr-abl-rearranged leukemias that do not demonstrate the classical Ph1 carry a poor prognosis that is similar to those that are Ph1-positive. Patients with Ph1-positive ALL are rarely cured with chemotherapy, although long-term survival is now being routinely reported when such patients are treated with combinations of chemotherapy and Bcr-abl tyrosine kinase inhibitors.

    Two other chromosomal abnormalities with poor prognosis are t(4;11), which is characterized by rearrangements of the MLL gene and may be rearranged despite normal cytogenetics, and t(9;22). In addition to t(4;11) and t(9;22), compared with patients with a normal karyotype, patients with deletion of chromosome 7 or trisomy 8 have been reported to have a lower probability of survival at 5 years.[13] In a multivariate analysis, karyotype was the most important predictor of disease-free survival.[13][Level of evidence: 3iiDii]

Late Effects of Treatment for Adult ALL

Long-term follow-up of 30 patients with ALL in remission for at least 10 years has demonstrated ten cases of secondary malignancies. Of 31 long-term female survivors of ALL or AML younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred.[14]

References:

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.

  2. Pui CH, Jeha S: New therapeutic strategies for the treatment of acute lymphoblastic leukaemia. Nat Rev Drug Discov 6 (2): 149-65, 2007.

  3. Peterson LC, Bloomfield CD, Brunning RD: Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia: a study of 28 patients. Am J Med 60(2): 209-220, 1976.

  4. Secker-Walker LM, Cooke HM, Browett PJ, et al.: Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood 72 (2): 784-91, 1988.

  5. Gaynor J, Chapman D, Little C, et al.: A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969. J Clin Oncol 6 (6): 1014-30, 1988.

  6. Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.

  7. Kantarjian HM, Walters RS, Smith TL, et al.: Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia. Blood 72 (5): 1784-9, 1988.

  8. Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001.

  9. Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996.

  10. Fenaux P, Lai JL, Miaux O, et al.: Burkitt cell acute leukaemia (L3 ALL) in adults: a report of 18 cases. Br J Haematol 71 (3): 371-6, 1989.

  11. Reiter A, Schrappe M, Ludwig WD, et al.: Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. Blood 80 (10): 2471-8, 1992.

  12. Chromosomal abnormalities and their clinical significance in acute lymphoblastic leukemia. Third International Workshop on Chromosomes in Leukemia. Cancer Res 43 (2): 868-73, 1983.

  13. Wetzler M, Dodge RK, Mrózek K, et al.: Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 93 (11): 3983-93, 1999.

  14. Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001.

Cellular Classification of Adult ALL

The following leukemic cell characteristics are important:

  • Morphological features.
  • Cytogenetic characteristics.
  • Immunologic cell surface and biochemical markers.
  • Cytochemistry.

In adults, French-American-British (FAB) L1 morphology (more mature-appearing lymphoblasts) is present in fewer than 50% of patients, and L2 morphology (more immature and pleomorphic) predominates.[1] L3 (Burkitt) ALL is much less common than the other two FAB subtypes. It is characterized by blasts with cytoplasmic vacuolizations and surface expression of immunoglobulin, and the bone marrow often has an appearance described as a “starry sky” owing to the presence of numerous apoptotic cells. L3 ALL is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).

Some patients presenting with acute leukemia may have a cytogenetic abnormality that is morphologically indistinguishable from the Philadelphia chromosome (Ph1).[2] The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of adults and a small percentage of children with ALL.[3] In the majority of children and in more than one-half of adults with Ph1-positive ALL, the molecular abnormality is different from that in Ph1-positive chronic myelogenous leukemia (CML).

Many patients who have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics. The bcr-abl fusion gene may be detectable only by pulsed-field gel electrophoresis or reverse-transcriptase polymerase chain reaction for the bcr-abl fusion gene because many patients have a different fusion protein from the one found in CML (p190 vs. p210).

Using heteroantisera and monoclonal antibodies, ALL cells can be divided into several subtypes (see Table 1 ).[1][4][5][6]

Table 1. Frequency of ALL Cell Subtypes

Cell Subtype

Approximate Frequency

Early B-cell lineage

80%

T cells

10%–15%

B cells with surface immunoglobulins

<5%

About 95% of all types of ALL (except Burkitt, which usually has an L3 morphology by the FAB classification) have elevated terminal deoxynucleotidyl transferase (TdT) expression. This elevation is extremely useful in diagnosis; if concentrations of the enzyme are not elevated, the diagnosis of ALL is suspect. However, 20% of cases of AML may express TdT; therefore, its usefulness as a lineage marker is limited. Because Burkitt leukemias are managed according to different treatment algorithms, it is important to specifically identify these cases prospectively by their L3 morphology, absence of TdT, and expression of surface immunoglobulin. Patients with Burkitt leukemias will typically have one of the following three chromosomal translocations:

  • t(8;14).
  • t(2;8).
  • t(8;22).

References:

  1. Brearley RL, Johnson SA, Lister TA: Acute lymphoblastic leukaemia in adults: clinicopathological correlations with the French-American-British (FAB) co-operative group classification. Eur J Cancer 15 (6): 909-14, 1979.

  2. Peterson LC, Bloomfield CD, Brunning RD: Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia: a study of 28 patients. Am J Med 60(2): 209-220, 1976.

  3. Secker-Walker LM, Cooke HM, Browett PJ, et al.: Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood 72 (2): 784-91, 1988.

  4. Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.

  5. Sobol RE, Royston I, LeBien TW, et al.: Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies. Blood 65 (3): 730-5, 1985.

  6. Foon KA, Billing RJ, Terasaki PI, et al.: Immunologic classification of acute lymphoblastic leukemia. Implications for normal lymphoid differentiation. Blood 56 (6): 1120-6, 1980.

Stage Information for Adult ALL

There is no clear-cut staging system for this disease. This disease is classified as untreated, in remission, or recurrent.

Untreated Adult ALL

For a newly diagnosed patient with no prior treatment, untreated adult ALL is defined by the following:

  • Abnormal white blood cell count and differential.
  • Abnormal hematocrit/hemoglobin and platelet counts.
  • Abnormal bone marrow with more than 5% blasts.
  • Signs and symptoms of the disease.

Adult ALL in Remission

A patient who has received remission-induction treatment of ALL is in remission if all of the following criteria are met:

  • Bone marrow is normocellular with no more than 5% blasts.
  • There are no signs or symptoms of the disease.
  • There are no signs or symptoms of central nervous system leukemia or other extramedullary infiltration.
  • All of the following laboratory values are within normal limits:
    • White blood cell count and differential.
    • Hematocrit/hemoglobin level.
    • Platelet count.

Treatment Option Overview

Successful treatment of ALL consists of the control of bone marrow and systemic disease and the treatment (or prevention) of sanctuary-site disease, particularly the central nervous system (CNS).[1][2] The cornerstone of this strategy includes systemically administered combination chemotherapy with CNS preventive therapy. CNS prophylaxis is achieved with chemotherapy (intrathecal and/or high-dose systemic therapy) and, in some cases, cranial radiation therapy.

Treatment is divided into the following three phases:

  • Remission induction.
  • CNS prophylaxis.
  • Postremission (also called remission continuation or maintenance).

The average length of treatment for ALL varies between 1.5 and 3 years in the effort to eradicate the leukemic cell population. Younger adults with ALL may be eligible for selected clinical trials for childhood ALL. (Refer to the PDQ summary on Childhood Acute Lymphoblastic Leukemia Treatment for more information.)

Entry into a clinical trial is highly desirable to assure adequate patient treatment and maximal information retrieval from the treatment of this highly responsive, but usually fatal, disease.

Table 2. Standard Treatment Options for Adult ALL

Disease Status

Standard Treatment Options

Untreated ALL

Remission induction therapy

CNS prophylaxis therapy

ALL in remission

Postremission therapy

CNS prophylaxis therapy

Recurrent ALL

Reinduction chemotherapy

Palliative radiation therapy

Dasatinib

CNS = central nervous system.

References:

  1. Clarkson BD, Gee T, Arlin ZA, et al.: Current status of treatment of acute leukemia in adults: an overview of the Memorial experience and review of literature. Crit Rev Oncol Hematol 4 (3): 221-48, 1986.

  2. Hoelzer D, Gale RP: Acute lymphoblastic leukemia in adults: recent progress, future directions. Semin Hematol 24 (1): 27-39, 1987.

Treatment for Untreated Adult ALL

Standard Treatment Options for Untreated Adult ALL

Standard treatment options for untreated adult ALL include the following:

  1. Remission induction therapy, including the following:
    • Combination chemotherapy.
    • Imatinib mesylate (for patients with Philadelphia chromosome [Ph1]-positive ALL).
    • Imatinib mesylate combined with combination chemotherapy (for patients with Ph1-positive ALL)
    • Supportive care.
  2. Central nervous system (CNS) prophylaxis therapy, including the following:
    • Cranial radiation therapy plus intrathecal (IT) methotrexate.
    • High-dose systemic methotrexate and IT methotrexate without cranial radiation therapy.
    • IT chemotherapy alone.

Remission induction therapy

Sixty percent to 80% of adults with ALL usually achieve a complete remission (CR) status following appropriate induction therapy. Appropriate initial treatment, usually consisting of a regimen that includes the combination of vincristine, prednisone, and an anthracycline, with or without asparaginase, results in a CR rate of up to 80%. In patients with Ph1-positive ALL, the remission rate is generally greater than 90% when standard induction regimens are combined with Bcr-abl tyrosine kinase inhibitors. In the largest study published to date of Ph1-positive ALL patients, overall survival (OS) for 1,913 adult ALL patients was 39% at 5 years.[1]

Patients who experience a relapse after remission usually die within 1 year, even if a second CR is achieved. If there are appropriate available donors and if the patient is younger than 55 years, bone marrow transplantation may be a consideration in the management of this disease.[2] Transplant centers performing five or fewer transplants annually usually have poorer results than larger centers.[3] If allogeneic transplant is considered, transfusions with blood products from a potential donor should be avoided, if possible. [4][5][6][7][8][9][10]

Combination chemotherapy

Most current induction regimens for patients with adult ALL include combination chemotherapy with prednisone, vincristine, and an anthracycline. Some regimens, including those used in a Cancer and Leukemia Group B (CALGB) study (CLB-8811), also add other drugs, such as asparaginase or cyclophosphamide. Current multiagent induction regimens result in complete response rates that range from 60% to 90%.[1][4][5][11][12]

Imatinib mesylate

Imatinib mesylate is often incorporated into the therapeutic plan for patients with Ph1-positive ALL. Imatinib mesylate, an orally available inhibitor of the BCR-ABL tyrosine kinase, has been shown to have clinical activity as a single agent in Ph1-positive ALL.[13][14][Level of evidence: 3iiiDiv] More commonly, particularly in younger patients, imatinib is incorporated into combination chemotherapy regimens. There are several published single-arm studies in which CR rate and survival are compared with historical controls.

Evidence (Imatinib mesylate):

Several studies have suggested that the addition of imatinib to conventional combination chemotherapy induction regimens results in complete response rates, event-free survival rates, and OS rates that are higher than those in historical controls.[15][16][17] At the present time, no conclusions can be drawn regarding the optimal imatinib dose or schedule.

  1. In a study of imatinib combined with chemotherapy from the Northern Italy Leukemia Group, patients with newly diagnosed, untreated Ph1-positive ALL were treated with an induction regimen containing idarubicin, vincristine, prednisone, and L-asparaginase.[18] After accrual of an initial cohort, the study was modified to include the use of imatinib (600 mg per day from days 15 to 21). In consolidation, patients received imatinib (600 mg per day for 7 days) beginning 3 days prior to the start of each course of chemotherapy.
    • For all patients who achieved remission, the intent was to proceed to allogeneic transplant when and if an HLA-matched donor could be identified. Patients lacking a donor received an autologous transplant. After completion of chemotherapy and transplant, all patients were to receive maintenance imatinib for as long as tolerated. After 20 patients had accrued to the imatinib arm, L-asparaginase was omitted from the induction regimen from both arms because of toxicity.
    • Outcomes for the first cohort of 35 patients (imatinib-free) were compared to those of the subsequent cohort of 59 (imatinib-treated) patients. For patients treated with imatinib, OS probability was 38% at 5 years (median, 3.1 years) versus 23% in the imatinib-free group (median, 1.1 years; P = .009).[18][Level of evidence: 3iii]
    • The drawbacks of this nonrandomized study are the small sample size (94 total patients) and the change in the treatment regimen (omission of L-asparaginase) midway through the study. However, the results suggest that inclusion of imatinib into a relatively standard chemotherapy regimen for newly diagnosed adult patients with Ph1-positive ALL may provide a significant survival advantage.
  2. In another study, ten patients with Ph1-positive ALL and ten patients with chronic myelogenous leukemia in lymphoid blast crisis were treated with doses of imatinib ranging from 300 mg to 1,000 mg per day.[13] Of these 20 patients, four had complete hematologic remission and ten had marrow responses. Responses were short lived, with the majority of these patients relapsing at a median of 58 days after the start of therapy.
  3. In another study, 48 patients with Ph1-positive ALL were treated with 400 mg to 800 mg of imatinib per day.[14] The overall response rate was 60%, with 9 out of 48 patients (19%) achieving a CR. The responses again were short, with a median duration of 2.2 months.

In each of these studies, common toxicities were nausea and liver enzyme abnormalities, which necessitated interruption and/or dose reduction of imatinib.[13][14] (Refer to the PDQ summary on Nausea and Vomiting for more information.) Subsequent allogeneic transplant does not appear to be adversely affected by the addition of imatinib to the treatment regimen.

Imatinib is generally incorporated into the treatment of patients with Ph1-positive ALL because of the responses observed in monotherapy trials. If a suitable donor is available, allogeneic bone marrow transplantation should be considered because remissions are generally short with conventional ALL chemotherapy clinical trials.

Supportive care

Since myelosuppression is an anticipated consequence of both leukemia and its treatment with chemotherapy, patients must be closely monitored during remission induction treatment. Facilities must be available for hematological support and for the treatment of infectious complications.

Supportive care during remission induction treatment should routinely include red blood cell and platelet transfusions, when appropriate.[19][20]

Evidence (Supportive care):

  1. Randomized clinical trials have shown similar outcomes for patients who received prophylactic platelet transfusions at a level of 10,000/mm3 rather than at a level of 20,000/mm3.[21]
  2. The incidence of platelet alloimmunization was similar among groups randomly assigned to receive one of the following from random donors:[22]
    • Pooled platelet concentrates.
    • Filtered, pooled platelet concentrates.
    • Ultraviolet B-irradiated, pooled platelet concentrates.
    • Filtered platelets obtained by apheresis.

Empiric broad-spectrum antimicrobial therapy is an absolute necessity for febrile patients who are profoundly neutropenic.[23][24] Careful instruction in personal hygiene and dental care and in recognizing early signs of infection are appropriate for all patients. Elaborate isolation facilities, including filtered air, sterile food, and gut flora sterilization, are not routinely indicated but may benefit transplant patients.[25][26]

Rapid marrow ablation with consequent earlier marrow regeneration decreases morbidity and mortality. White blood cell transfusions can be beneficial in selected patients with aplastic marrow and serious infections that are not responding to antibiotics.[27] Prophylactic oral antibiotics may be appropriate in patients with expected prolonged, profound granulocytopenia (<100/mm3 for 2 weeks), though further studies are necessary.[28] Serial surveillance cultures may be helpful in detecting the presence or acquisition of resistant organisms in these patients.

As suggested in a CALGB study (CLB-9111), the use of myeloid growth factors during remission-induction therapy appears to decrease the time to hematopoietic reconstitution.[29][30]

CNS prophylaxis therapy

The early institution of CNS prophylaxis is critical to achieve control of sanctuary disease.

Special Considerations for B-Cell and T-Cell Adult ALL

Two additional subtypes of adult ALL require special consideration. B-cell ALL, which expresses surface immunoglobulin and cytogenetic abnormalities such as t(8;14), t(2;8), and t(8;22), is not usually cured with typical ALL regimens. Aggressive brief-duration high-intensity regimens, including those previously used in CLB-9251 (NCT00002494), that are similar to those used in aggressive non-Hodgkin lymphoma have shown high response rates and cure rates (75% CR; 40% failure-free survival).[31][32][33] Similarly, T-cell ALL, including lymphoblastic lymphoma, has shown high cure rates when treated with cyclophosphamide-containing regimens.[4]

Whenever possible, patients with B-cell or T-cell ALL should be entered in clinical trials designed to improve the outcomes in these subsets. (Refer to the Burkitt Lymphoma/Diffuse Small Noncleaved-cell Lymphoma and Lymphoblastic lymphoma sections in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated adult acute lymphoblastic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Goldstone AH, Richards SM, Lazarus HM, et al.: In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 111 (4): 1827-33, 2008.

  2. Bortin MM, Horowitz MM, Gale RP, et al.: Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s. JAMA 268 (5): 607-12, 1992.

  3. Horowitz MM, Przepiorka D, Champlin RE, et al.: Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? Blood 79 (10): 2771-4, 1992.

  4. Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995.

  5. Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991.

  6. Barrett AJ, Horowitz MM, Gale RP, et al.: Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 74 (2): 862-71, 1989.

  7. Dinsmore R, Kirkpatrick D, Flomenberg N, et al.: Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia. Blood 62 (2): 381-8, 1983.

  8. Jacobs AD, Gale RP: Recent advances in the biology and treatment of acute lymphoblastic leukemia in adults. N Engl J Med 311 (19): 1219-31, 1984.

  9. Doney K, Buckner CD, Kopecky KJ, et al.: Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission. Bone Marrow Transplant 2 (4): 355-63, 1987.

  10. Vernant JP, Marit G, Maraninchi D, et al.: Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission. J Clin Oncol 6 (2): 227-31, 1988.

  11. Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.

  12. Kantarjian H, Thomas D, O'Brien S, et al.: Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101 (12): 2788-801, 2004.

  13. Druker BJ, Sawyers CL, Kantarjian H, et al.: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344 (14): 1038-42, 2001.

  14. Ottmann OG, Druker BJ, Sawyers CL, et al.: A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100 (6): 1965-71, 2002.

  15. Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004.

  16. Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006.

  17. Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006.

  18. Bassan R, Rossi G, Pogliani EM, et al.: Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol 28 (22): 3644-52, 2010.

  19. Slichter SJ: Controversies in platelet transfusion therapy. Annu Rev Med 31: 509-40, 1980.

  20. Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 (3): 529-34, 1986.

  21. Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 337 (26): 1870-5, 1997.

  22. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 337 (26): 1861-9, 1997.

  23. Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161 (3): 381-96, 1990.

  24. Rubin M, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 (2): 167-84, 1988.

  25. Armstrong D: Symposium on infectious complications of neoplastic disease (Part II). Protected environments are discomforting and expensive and do not offer meaningful protection. Am J Med 76 (4): 685-9, 1984.

  26. Sherertz RJ, Belani A, Kramer BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 83 (4): 709-18, 1987.

  27. Schiffer CA: Granulocyte transfusions: an overlooked therapeutic modality. Transfus Med Rev 4 (1): 2-7, 1990.

  28. Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N Engl J Med 304 (18): 1057-62, 1981.

  29. Scherrer R, Geissler K, Kyrle PA, et al.: Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). Ann Hematol 66 (6): 283-9, 1993.

  30. Larson RA, Dodge RK, Linker CA, et al.: A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92 (5): 1556-64, 1998.

  31. Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996.

  32. Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001.

  33. Thomas DA, Cortes J, O'Brien S, et al.: Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol 17 (8): 2461-70, 1999.

Treatment for Adult ALL in Remission

Standard Treatment Options for Adult ALL in Remission

Standard treatment options for adult ALL in remission include the following:

  1. Postremission therapy, including the following:
    • Chemotherapy.
    • Ongoing treatment with a Bcr-abl tyrosine kinase inhibitor such as imatinib, nilotinib, or dasatinib.
    • Autologous or allogeneic bone marrow transplant (BMT).
  2. Central nervous system (CNS) prophylaxis therapy, including the following:
    • Cranial radiation therapy plus intrathecal (IT) methotrexate.
    • High-dose systemic methotrexate and IT methotrexate without cranial radiation therapy.
    • IT chemotherapy alone.

Postremission therapy

Current approaches to postremission therapy for adult ALL include short-term, relatively intensive chemotherapy followed by any of the following:

  • Longer-term therapy at lower doses (maintenance therapy).
  • Allogeneic bone marrow transplant.

Because the optimal postremission therapy for patients with ALL is still unclear, participation in clinical trials should be considered. (Refer to the B-cell (Burkitt) lymphoma section in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)

Evidence (Chemotherapy):

  1. Several trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (ECOG-2993), of aggressive postremission chemotherapy for adult ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40%.[1][2][3][4][5][6][7]
    • In two series,[4][5] especially good prognoses were found for patients with T-cell lineage ALL, with DFS rates of 50% to 70% for patients receiving postremission therapy.
    • These series represent a significant improvement in DFS rates over previous, less intensive chemotherapeutic approaches.
  2. In contrast, poor cure rates were demonstrated in patients with Philadelphia chromosome (Ph1)-positive ALL, B-cell lineage ALL with an L3 phenotype (surface immunoglobulin positive), and B-cell lineage ALL characterized by t(4;11).

Administration of the newer dose-intensive schedules can be difficult and should be performed by physicians experienced in these regimens at centers equipped to deal with potential complications. Studies in which continuation or maintenance chemotherapy was eliminated had outcomes inferior to those with extended treatment durations.[8][9] Imatinib has been incorporated into maintenance regimens in patients with Ph1-positive ALL.[10][11][12]

Evidence (Allogeneic and autologous BMT):

AlloBMT results in the lowest incidence of leukemic relapse, even when compared with a BMT from an identical twin (syngeneic BMT). This finding has led to the concept of an immunologic graft-versus-leukemia effect similar to graft-versus-host disease (GVHD). The improvement in DFS in patients undergoing alloBMT as primary postremission therapy is offset, in part, by the increased morbidity and mortality from GVHD, veno-occlusive disease of the liver, and interstitial pneumonitis.[13]

  1. The results of a series of retrospective and prospective studies published between 1987 and 1994 suggest that alloBMT or autoBMT as postremission therapy offer no survival advantage over intensive chemotherapy, except perhaps for patients with high-risk or Ph1-positive ALL.[14][15][16][17] This was confirmed in the ECOG-2993 study.[7]
    • The use of alloBMT as primary postremission therapy is limited by both the need for an HLA-matched sibling donor and the increased mortality from alloBMT in patients in their fifth or sixth decade.
    • The mortality from alloBMT using an HLA-matched sibling donor in these studies ranged from 20% to 40%.
  2. Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched as an attempt to examine the role of transplant as postremission therapy for ALL more definitively; patients were accrued from 1993 to 2006.[7] Patients with Ph1-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1][2][3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent alloBMT as consolidation therapy. Those patients lacking a donor were randomly assigned to receive either an autoBMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS); event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.
    1. Ninety percent of patients in this study achieved remission after induction therapy. Of these patients, 443 had an HLA-identical sibling, 310 of whom underwent an alloBMT. For the 456 patients in remission who were eligible for transplant but lacked a donor, 227 received chemotherapy alone, while 229 underwent an autoBMT.
    2. By donor-to-no-donor analysis, standard-risk ALL patients with an HLA-identical sibling had a 5-year OS of 53% compared with 45% for patients lacking a donor (P = .01).
    3. In a subgroup analysis, the advantage for patients with standard-risk ALL who had donors remained significant (OS = 62% vs. 52%; P = .02).
      • For patients with high-risk disease (older than 35 years or high WBC count), the difference in OS was 41% versus 35% (donor vs. no donor), but was not significant (P = .2).
      • Relapse rates were significantly lower (P < .00005) for both standard- and high-risk patients with HLA-matched donors.
    4. In contrast to alloBMT, autoBMT was less effective than maintenance chemotherapy as postremission treatment (5-year OS = 46% for chemotherapy vs. 37% for autoBMT; P = .03).
    5. The results of this trial suggest the existence of a graft-versus-leukemia effect for adult Ph1-negative ALL and support the use of sibling donor alloBMT as the consolidation therapy providing the greatest chance for long-term survival for patients with standard-risk adult ALL in first remission.[7][Level of evidence: 2A]
    6. The results also suggest that in the absence of a sibling donor, maintenance chemotherapy is preferable to autoBMT as postremission therapy.[7][Level of evidence: 2A]

The use of matched unrelated donors for alloBMT is currently under evaluation but, because of its current high treatment-related morbidity and mortality, it is reserved for patients in second remission or beyond. The dose of total-body radiation therapy administered is associated with the incidence of acute and chronic GVHD and may be an independent predictor of leukemia-free survival.[18][Level of evidence: 3iiB]

Evidence (B-cell ALL):

Aggressive cyclophosphamide-based regimens similar to those used in aggressive non-Hodgkin lymphoma have shown improved outcome of prolonged DFS for patients with B-cell ALL (L3 morphology, surface immunoglobulin positive).[19]

  1. Retrospectively reviewing three sequential cooperative group trials from Germany, one group of investigators found the following:[19]
    • A marked improvement in survival, from zero survivors in a 1981 study that used standard pediatric therapy and lasted 2.5 years, to a 50% survival rate in two subsequent trials that used rapidly alternating lymphoma-like chemotherapy and were completed within 6 months.

CNS prophylaxis therapy

The early institution of CNS prophylaxis is critical to achieve control of sanctuary disease. Some authors have suggested that there is a subgroup of patients at low risk for CNS relapse for whom CNS prophylaxis may not be necessary. However, this concept has not been tested prospectively.[20]

Aggressive CNS prophylaxis remains a prominent component of treatment.[19] This report, which requires confirmation in other cooperative group settings, is encouraging for patients with L3 ALL. Patients with surface immunoglobulin and L1 or L2 morphology did not benefit from this regimen. Similarly, patients with L3 morphology and immunophenotype, but unusual cytogenetic features, were not cured with this approach. A WBC count of less than 50,000 per microliter predicted improved leukemia-free survival in a univariate analysis.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult acute lymphoblastic leukemia in remission. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Gaynor J, Chapman D, Little C, et al.: A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969. J Clin Oncol 6 (6): 1014-30, 1988.

  2. Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.

  3. Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991.

  4. Zhang MJ, Hoelzer D, Horowitz MM, et al.: Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee. Ann Intern Med 123 (6): 428-31, 1995.

  5. Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995.

  6. Kantarjian H, Thomas D, O'Brien S, et al.: Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101 (12): 2788-801, 2004.

  7. Goldstone AH, Richards SM, Lazarus HM, et al.: In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 111 (4): 1827-33, 2008.

  8. Cuttner J, Mick R, Budman DR, et al.: Phase III trial of brief intensive treatment of adult acute lymphocytic leukemia comparing daunorubicin and mitoxantrone: a CALGB Study. Leukemia 5 (5): 425-31, 1991.

  9. Dekker AW, van't Veer MB, Sizoo W, et al.: Intensive postremission chemotherapy without maintenance therapy in adults with acute lymphoblastic leukemia. Dutch Hemato-Oncology Research Group. J Clin Oncol 15 (2): 476-82, 1997.

  10. Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004.

  11. Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006.

  12. Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006.

  13. Finiewicz KJ, Larson RA: Dose-intensive therapy for adult acute lymphoblastic leukemia. Semin Oncol 26 (1): 6-20, 1999.

  14. Horowitz MM, Messerer D, Hoelzer D, et al.: Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. Ann Intern Med 115 (1): 13-8, 1991.

  15. Sebban C, Lepage E, Vernant JP, et al.: Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol 12 (12): 2580-7, 1994.

  16. Forman SJ, O'Donnell MR, Nademanee AP, et al.: Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 70 (2): 587-8, 1987.

  17. Fière D, Lepage E, Sebban C, et al.: Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia. J Clin Oncol 11 (10): 1990-2001, 1993.

  18. Corvò R, Paoli G, Barra S, et al.: Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant. Int J Radiat Oncol Biol Phys 43 (3): 497-503, 1999.

  19. Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996.

  20. Kantarjian HM, Walters RS, Smith TL, et al.: Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia. Blood 72 (5): 1784-9, 1988.

Treatment for Recurrent Adult ALL

Standard Treatment Options for Recurrent Adult ALL

Standard treatment options for recurrent adult ALL include the following:

  1. Reinduction chemotherapy followed by allogeneic bone marrow transplantation (alloBMT).
  2. Palliative radiation therapy (for patients with symptomatic recurrence).
  3. Dasatinib (for patients with Philadelphia chromosome [Ph1]-positive ALL).

Reinduction chemotherapy

Patients with ALL who experience a relapse following chemotherapy and maintenance therapy are unlikely to be cured by further chemotherapy alone. These patients should be considered for reinduction chemotherapy followed by alloBMT.

Palliative radiation therapy

Low-dose palliative radiation therapy may be considered in patients with symptomatic recurrence either within or outside the central nervous system.[1]

Dasatinib

Patients with Ph1-positive ALL will often be taking imatinib at the time of relapse and thus will have imatinib-resistant disease. Dasatinib, a novel tyrosine kinase inhibitor with efficacy against several different imatinib-resistant BCR-ABL mutations, has been approved for use in Ph1-positive ALL patients who are resistant to or intolerant of imatinib. The approval was based on a series of trials involving patients with chronic myelogenous leukemia, one of which included small numbers of patients with lymphoid blast crisis or Ph1-positive ALL.

Evidence (Dasatinib):

  1. In one study, ten patients were treated with dose-escalated dasatinib.[2] Seven of these patients had a complete hematologic response (<5% marrow blasts with normal peripheral blood cell counts), three of whom had a complete cytogenetic response.
    • The common toxicities were reversible myelosuppression (89%) and pleural effusions (21%).
    • Virtually all of these patients relapsed within 6 months of the start of treatment with dasatinib.

Treatment Options Under Clinical Evaluation for Recurrent Adult ALL

Patients for whom an HLA-matched donor is not available are excellent candidates for enrollment in clinical trials that are studying the following:[3][4][5][6][7][8][9]

  1. Autologous transplantation.
  2. Immunomodulation.
  3. Novel chemotherapeutic or biological agents.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult acute lymphoblastic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Gray JR, Wallner KE: Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia. Int J Radiat Oncol Biol Phys 19 (2): 439-44, 1990.

  2. Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354 (24): 2531-41, 2006.

  3. Herzig RH, Bortin MM, Barrett AJ, et al.: Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. Lancet 1 (8536): 786-9, 1987.

  4. Thomas ED, Sanders JE, Flournoy N, et al.: Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up. Blood 62 (5): 1139-41, 1983.

  5. Barrett AJ, Horowitz MM, Gale RP, et al.: Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 74 (2): 862-71, 1989.

  6. Dinsmore R, Kirkpatrick D, Flomenberg N, et al.: Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia. Blood 62 (2): 381-8, 1983.

  7. Sallan SE, Niemeyer CM, Billett AL, et al.: Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 7 (11): 1594-601, 1989.

  8. Paciucci PA, Keaveney C, Cuttner J, et al.: Mitoxantrone, vincristine, and prednisone in adults with relapsed or primarily refractory acute lymphocytic leukemia and terminal deoxynucleotidyl transferase positive blastic phase chronic myelocytic leukemia. Cancer Res 47 (19): 5234-7, 1987.

  9. Biggs JC, Horowitz MM, Gale RP, et al.: Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 80 (4): 1090-3, 1992.


This information is provided by the National Cancer Institute.

This information was last updated on February 21, 2014.

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