Acute lymphocytic leukemia


An in-depth report on the causes, diagnosis, treatment, and prevention of leukemia.

Alternative Names

Acute lymphoblastic (or lymphocytic) leukemia


Acute Lymphocytic Leukemia (ALL)

There are four major types of leukemia. ALL is the most common in children, and the least common in adults. About 6,000 people are diagnosed with ALL each year. Children account for two-thirds of these cases. In general, children with ALL have a better outlook than adults. Most children with ALL can be cured of this cancer.

Symptoms and Diagnosis

Symptoms of ALL include fatigue, pale skin, recurrent infections, bone pain, bruising, and small red spots under the skin. Doctors use various tests, including blood counts and bone marrow biopsies, to diagnose ALL.


ALL is treated with chemotherapy and, sometimes, radiation. Children receive different chemotherapy regimens than adults. Some patients with advanced cancer that has not responded to these treatments may need a stem cell transplant.

Infection Prevention

Both chemotherapy and transplantation increase the risk for infection. Patients must take strict precautions to avoid exposure to germs. Ways to prevent infection include:

  • Practice good hygiene including regular handwashing and dental care (such as brushing and flossing).
  • Avoid crowds, especially during cold and flu season.
  • Eat only well-cooked foods (no raw fruits or vegetables or undercooked poultry, meat, or fish).
  • Boil tap water before drinking it.
  • Do not keep fresh flowers or plants in your house as they may carry mold.
  • Make sure you are up to date with vaccinations. Patients may benefit from repeat or booster immunizations.

New Drug Approvals

In 2012, the FDA approved two new drugs for treatment of adults with relapsed or refractory ALL:

  • Ponatinib (Iclusig) is the newest tyrosine kinase inhibitor (TKI) drug approved for patients with Philadelphia chromosome-positive ALL. Ponatinib is approved for patients who have not been helped by other TKI drugs such as imatinib or dasatinib. It is a pill taken once a day.
  • Marqibo is a specially-formulated type of vincristine (a standard cancer drug) that is approved for patients with Philadelphia chromosome-negative ALL. It is given as weekly injections.


The word leukemia literally means "white blood" and is used to describe a variety of cancers that begin in the blood-forming cells (lymphocytes) of the bone marrow.

Leukemias are divided into two major types:

  • Acute (which progresses quickly with many immature white cells)
  • Chronic (which progresses more slowly and has more mature white cells)

Both leukemia and lymphomas (Hodgkin’s disease and non-Hodgkin’s lymphomas) are cancers of lymphocytes. The difference is that leukemia starts in the bone marrow while lymphomas originate in lymph nodes and then spread to the bone marrow or other organs.

White blood cells (leukocytes) evolve from immature cells referred to as blasts. Malignancy of these blast cells is the source of leukemias, which generally progress as follows:

  • Normally, blasts constitute 5% or less of healthy bone marrow. In leukemia, however, these blasts remain immature and multiply continuously but fail to mature properly, eventually constituting between 30 - 100% of the bone marrow.
  • In time, these malignant blast cells fill up the bone marrow and prevent production of healthy red cells, platelets, and mature white cells (leukocytes).

Malignant blasts spill out of the marrow into the bloodstream and lymph system and can travel to the brain and spinal cord (the central nervous system). Some blasts are called lymphoblasts (which normally become mature cells called lymphocytes) and others are called myeloblasts (which mature to myeloid cells).

Acute leukemias subdivided into two classifications according to whether the malignant blasts are lymphocytes or myeloid:

  • Acute lymphocytic leukemia (ALL), which is the subject of this report
  • Acute myeloid leukemia (AML), which is not covered in this report

Acute Lymphocytic Leukemia

Acute lymphocytic leukemia (ALL) is also known as acute lymphoid leukemia or acute lymphoblastic leukemia. The majority of childhood leukemias are of the ALL type.

Lymphocytes are the body’s primary immune cells. Among other vital functions, lymphocytes produce antibodies, factors that can target and attack specific foreign substances (antigens) and fight infections.

Lymphocytes develop in the thymus gland or bone marrow and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).  ALL can arise from either T-cell or B-cell lymphocytes. Most cases of ALL involve B cells.


Doctors do not know exactly what causes acute lymphocytic leukemia (ALL). It is likely that ALL develops from a combination of genetic, biologic, and environmental factors.

Genetic Translocations

Up to 65% of leukemias contain genetic rearrangements, called translocations, in which some of the genetic material (genes) on a chromosome may be shuffled or swapped between a pair of chromosomes.

  • The most common genetic translocation in ALL is the Philadelphia (Ph) chromosome where DNA is swapped between chromosomes 9 and 22 [t(9:22)]. It occurs in about 20 - 30% of adults and 3 - 5% of children with ALL.
  • Another common translocation in ALL is t(12;21), which is referred to as TEL-AML1 fusion. It occurs in about 20% of patients with ALL.

Risk Factors

Acute lymphocytic leukemia is diagnosed in about 6,000 Americans each year. Children account for two-thirds of these new cases.


ALL in Children. ALL is the most common type of cancer diagnosed in children. ALL accounts for about 75% of cases of childhood leukemia. Each year, about 3,500 American children and adolescents are diagnosed with ALL. ALL can strike children of all ages, but it is most likely to occur before age 5 years. It is slightly more common in boys than in girls.

ALL in Adults. ALL is the least common type of leukemia among adults. About 1 in 3 cases of ALL occur in adults. Adults over age 50 have a higher risk for ALL than those between the ages of 20 - 50.

Race and Ethnicity

Caucasian and Hispanic children have a higher risk for ALL than African-American children.

Hereditary Disorders

ALL does not appear to run in families. Still, certain genetic disorders may increase risk. For example, children with Down syndrome have a 20-times greater risk of developing ALL than the general population. Other rare genetic disorders associated with increased risk include Klinefelter syndrome, Bloom syndrome, Fanconi anemia, ataxia-telangiectasia, neurofibromatosis, Shwachman syndrome, IgA deficiency, and congenital X-linked agammaglobulinemia.

Radiation and Chemical Exposure

Previous cancer treatment with high doses of radiation or chemotherapy can increase the risk for developing ALL. Prenatal exposure to x-rays may also increase risk in children. Lower levels of radiation (living near power lines, video screen emissions, small appliances, cell phones) are unlikely to pose any cancer risk.


The symptoms of ALL may be difficult to recognize. ALL usually begins abruptly and intensely, but in some cases symptoms may develop slowly. They may be present one day, and absent the next, particularly in children. Symptoms develop when:

  • There are not enough healthy mature white blood cells (leukocytes) to mount a defense against infection.
  • There are not enough healthy blood-clotting cells (platelets) to prevent bleeding.
  • The depleted oxygen-bearing red blood cells can't provide enough oxygen to organs.

Symptoms include:

  • Fatigue
  • Paleness -- patients may have poor coloring from anemia caused by insufficient red blood cells
  • Recurrent minor infections
  • Fever without known cause
  • Bone pain
  • Abdominal swelling
  • Bruising -- may result from only slight injury
  • Poor healing of minor cuts
  • Uncontrolled bleeding -- bleeding events increase as the bone marrow fails to produce enough platelets to make a normal blood clot, a condition called thrombocytopenia.
  • Small, red spots on the skin (petechiae)
  • Vision changes (rare)


ALL is diagnosed based on various tests.

Physical Examination

The doctor will examine a patient for signs of enlarged lymph nodes or enlarged liver or spleen. The doctor will also look for any signs of bruising or bleeding.

Blood Tests

A complete blood cell count (CBC), which checks for numbers of white cells, red blood cells, and platelets, is the first step in diagnosing ALL. Patients with ALL generally have a higher than normal white blood count and lower than normal red blood cell and platelet counts.

Blood tests are also performed to evaluate liver, kidney, and blood clotting status and to check for levels of certain minerals and proteins.

Bone Marrow Biopsy

If blood test results are abnormal or the doctor suspects leukemia despite normal cell counts, a bone marrow aspiration and biopsy are the next steps. These are very common and safe procedures. However, because this test can produce considerable anxiety, particularly in children, parents may want to ask the doctor if sedation is appropriate for their child.

  • A local anesthetic is given.
  • A needle is inserted into the bone, usually the rear hipbone. There may be brief pressure or pain. A small amount of marrow is withdrawn. Marrow looks like blood.
  • A larger needle is then inserted into the same place and pushed down to the bone. The doctor will rotate the needle to obtain a specimen for the biopsy. The patient will feel some pressure.
  • The sample is then taken to the lab to be analyzed. All the results are completed within a couple of days.

Normal bone marrow contains 5% or less of blast cells (the immature cells that ordinarily develop into healthy blood cells). In leukemia, abnormal blasts constitute between 30 - 100% of the marrow.

Spinal Tap

If bone marrow examination confirms ALL, a spinal tap (lumbar puncture) may be performed, which uses a needle inserted into the spinal canal. The patient feels some pressure and usually must lie flat for about an hour afterward to prevent severe headache. This can be difficult, particularly for children, so parents should plan reading or other quiet activities that will divert the child during that time. Parents should also be certain that the doctor performing this test is experienced in this procedure.

A sample of cerebrospinal fluid with leukemia cells is a sign that the disease has spread to the central nervous system. In most cases of childhood ALL, leukemia cells are not found in the cerebrospinal fluid.

Tests Performed after Diagnosis

Once a diagnosis of leukemia has been made, further tests are performed on the bone marrow cells:

  • Cytochemistry, flow cytometry, immunocytochemistry, and immunophenotyping tests are used to to identify and classify specific types of leukemia. For example, cytochemistry distinguishes lymphocytic leukemia cells from myeloid leukemia cells. Immunophenotyping shows if ALL cells are T cells or B cells based on the antigen located on the surface of the cell.
  • Cytogenetics and fluorescent in situ hybridization (FISH) are used for genetic analysis. Cytogenetic testing can detect translocations (such as Philadelphia chromosome) and other genetic abnormalities. FISH is used to identify specific changes within chromosomes. Genetic variations may help determine response to treatment.

An antigen is a substance that can provoke an immune response. Typically, antigens are substances not normally present in the body.

Cell Classification

The results of cytogenetic, flow cytometry, immunophenotyping, and other tests can help provide information on types and subtypes of ALL cells. The particular subtype of cell can aid in determining prognosis and treatment.

An older classification system called the French-American-British (FAB) classification grouped ALL into L1, L2, and L3 subtypes. A newer classification system classifies ALL B cells or T cells based on their stage of maturity.

B-Cell ALL Subtype Classification:

  • Early Pre-B
  • Common ALL
  • Pre-B ALL
  • Mature B-cell ALL (Also called Burkitt leukemia)

T-Cell ALL Subtype Classification:

  • Pre-T ALL
  • Mature T-cell ALL


Acute lymphocytic leukemia is responsible for about 1,400 deaths a year in the U.S., and it can progress quickly if untreated. However, ALL is one of the most curable cancers and survival rates are now at an all-time high.

According to the American Cancer Society, certain factors can help determine prognosis:

  • Age. Children have a better chance for recovery than adult patients. More than 95% of children with ALL attain remission. Among adults, younger patients (especially those younger than age 50) have a better prognosis than older patients.
  • Initial white blood cell (WBC) count. People diagnosed with a WBC count below 50,000 tend to do better than people with higher WBC counts.
  • ALL subtype. The subtype of T cell or B cell affects prognosis. For example, patients with T-cell ALL tend to have a better prognosis than those with mature B-cell ALL (Burkitt leukemia).
  • Chromosome translocations. People who have Philadelphia chromosome-positive ALL tend to have a poorer prognosis, although new treatments are helping many of these patients achieve remission.
  • Response to chemotherapy. Patients who achieve complete remission (absence of active cancer) within 4 - 5 weeks of starting treatment tend to have a better prognosis than those who take longer. Patients who do not achieve remission at any time have a poor prognosis. Evidence of minimal residual disease (presence of leukemia cells in the bone marrow) may also affect prognosis.

Other factors, such as central nervous system involvement or recurrence, may indicate a poorer prognosis.


Treatment Phases

There are typically three treatment stages for the average-risk patient with ALL:

  • Induction therapy is given in order to achieve a first remission (the absence of active cancer)
  • Consolidation (intensification) therapy is given to prevent relapse after remission has been achieved
  • Maintenance treatment is lower intensity therapy given for several years to prevent relapse after remission

Because leukemia can also spread to the brain and spinal cord, where chemotherapy that is given intravenously or orally does not penetrate very well, most patients also need radiation to the brain and spinal cord, or chemotherapy that is injected into the layers around them. This is called central nervous system prophylaxis (preventive treatment) and is given during all treatment phases to prevent the cancer from spreading to the brain and spinal cord.

Specific Treatments Used in ALL

The following are specific treatments used for ALL:

  • Chemotherapy is the primary treatment for each stage. Newer drugs known as biological therapies are also being used.
  • Radiation to the brain and spinal cord is also administered in some cases.
  • A bone marrow transplant may be recommended for some adult patients after treatment when there is no active cancer (remission) or for adults and children if the cancer has returned after treatment (relapsed).

Treatment to Achieve Remission (Induction Therapy)

The aim of induction therapy, the first treatment phase, is to reduce the number of leukemia cells to undetectable levels. The general guidelines for induction therapy are as follows:

  • Patients are given intensive chemotherapy that uses powerful multi-drug regimens. (Infants require special regimens not discussed here.)
  • For both children and adults, some of these therapies are administered orally, others intravenously.
  • Hospitalization is usually necessary at some point to help prevent infection and to give transfusions of blood, platelets, and other blood products. However, much of this therapy can be given on an outpatient basis.
  • After the first cycle of induction, bone marrow tests are done to determine if the patient is in remission.
  • Another bone marrow test is sometimes performed about a week later to confirm the first results.
  • A bone marrow transplant is considered for select patients who do not respond to induction treatment.

Drugs Used for Induction Chemotherapy

Both children and adults typically start with a 3-drug regimen. Imatinib (Gleevec) or dasatinib (Sprycel) may be added for patients with Philadelphia chromosome-positive ALL.

For children, the standard drugs are:

  • Vincristine (Oncovin), a vinca alkaloid drug
  • Prednisone or dexamethasone. These drugs are corticosteroids.
  • Asparaginase. It is generally provided as pegaspargase (Oncaspar) rather than L-asparaginase (Elspar) for treating newly diagnosed ALL in children.

For adults, the standard drugs are:

  • Vincristine
  • Prednisone
  • Anthracycline drug, such as such as doxorubicin, daunorubicin, or epirubicin. Some adult chemotherapy regimens also add on an asparaginase drug or cyclophosphamide (Cytoxan).

Preventing Central Nervous System Disease (CNS Prophylaxis)

Chemotherapy given intravenously or orally does not penetrate the blood-brain barrier sufficiently to destroy leukemic cells in the brain. Since the brain is one of the first sites for relapsing leukemia, preventive treatment is administered to the brain, spine, and testes (called sanctuary disease sites). This is called CNS prophylaxis.

For children, CNS prophylaxis uses intrathecal chemotherapy, in which a drug is injected directly into the spinal fluid. Intrathecal chemotherapy is given with methotrexate alone or a combination of methotrexate (MTX), cytarabine, and hydrocortisone.

Some high-risk children may  receive radiation to the skull (cranial radiation), radiation to the spine, or both along with intrathecal chemotherapy. This combination can be very toxic and is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. Long-term complications of high-dose cranial radiation can include learning and neurologic problems. Cranial radiation is also associated with increased risks for stroke and secondary cancers.

Adult CNS prophylaxis is performed in one of three ways:

  • Cranial radiation plus intrathecal chemotherapy with methotrexate
  • High-dose systemic infusion of methotrexate plus intrathecal methotrexate without cranial radiation
  • Intrathecal methotrexate chemotherapy alone

Evidence of Remission after Induction Treatment

Survival in acute leukemia depends on complete remission (no signs of active cancer). Although not always clear-cut, remission is indicated by the following:

  • All signs and symptoms of leukemia disappear.
  • There are no abnormal cells in the blood, bone marrow, and cerebrospinal fluid.
  • The percentage of blast cells in the bone marrow is less than 5%.
  • Blood platelet count returns to normal.

Induction can produce extremely rapid results. Nearly all children with ALL achieve remission after a month of induction treatment. The shorter the time to remission the better the outlook:

  • A complete remission usually occurs within the first 4 weeks. Patients who show low disease levels within 7 - 14 days have an excellent outlook, particularly if they have favorable genetic factors, and may need less-intensive treatments afterward.
  • Patients with high disease levels at 14 days or who require more than 4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment.

Side Effects and Complications

Side effects and complications of any chemotherapeutic regimen and radiation therapy are common, are more severe with higher doses, and increase over the course of treatment. Administering drugs for shorter duration can sometimes reduce toxicities without affecting the drugs' cancer-killing effects.

Common Side Effects. Typical side effects include:

  • Nausea and vomiting. Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects.
  • Diarrhea
  • Hair loss
  • Mouth sores
  • Weight loss
  • Depression

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used.

Infection from suppression of the immune system or from severe drops in white blood cells is a common and serious side effect. Patients should make all efforts to prevent infection. The patient at high risk for infection may need potent antibiotics and antifungal medications as well as granulocyte colony-stimulating factors or G-CSF (lenograstim, filgrastim) to stimulate the growth of infection-fighting white blood cells. Patients should make all efforts to minimize exposure to bacteria and viruses. (See “Preventing Infection” in the Home Management section of this report.)

Other serious side effects include:

  • Liver and kidney damage
  • Immediate and short-term risks of radiation therapy may include seizures, stroke, and paralysis
  • Very high levels of uric acid in the blood, which can damage the kidneys
  • Very high levels of calcium in the blood, which can impair heart function
  • Abnormal blood clotting
  • Allergic reaction
  • Low blood sugar (hypoglycemia) -- a rare complication in young, thin children who are taking purine analogues such as mercaptopurine and thioguanine
  • Suppression of adrenal glands in children who take short-term, high-dose corticosteroids such as prednisolone
  • Dasatinib  can increase the risk of increased pressure in the arteries of the lungs (pulmonary arterial hypertension)

Long-Term Complications.

  • Fatigue is very common after chemotherapy and can be significant and long-lasting.
  • Combinations of intrathecal chemotherapy plus brain radiation in children can cause some serious complications, including seizures and problems in learning and concentration.
  • Delayed puberty. The effects of treatment in the brain can affect regions that regulate reproductive hormones, which may affect fertility later on. Chemotherapy, cranial radiation, or both can impair fertility in male and female patients. Cranial radiation can also result in impaired growth.
  • Bone density loss can occur after chemotherapy, particularly with corticosteroids and after bone marrow transplantation.
  • Heart damage. Some of the treatments increase risk factors for future heart disease, including unhealthy cholesterol levels and high blood pressure. Patients treated for ALL should be regularly monitored for heart risks.
  • Stroke. Survivors of childhood leukemia are at increased risk of later stroke, especially if they received treatment with cranial radiation.
  • Secondary Cancers. Survivors of childhood ALL are at increased risk of later developing other types of cancers, including brain and spinal cord tumors, basal cell skin carcinoma, and myeloid (bone marrow) malignancies. Radiation and older types of chemotherapy are mainly responsible for this risk. Newer types of ALL treatment may be less likely to cause secondary cancers.

Treatment During Remission (Consolidation and Maintenance)

Consolidation and maintenance therapies follow induction and first remission. The goal of consolidation and maintenance therapies is to prevent a relapse.

Consolidation (Intensification) Therapy

Because there is a high risk of the cancer returning (relapsing) after the first phase of treatment (induction therapy), an additional course of treatment is given next. This is called consolidation therapy (also called intensification therapy). Consolidation is an intense chemotherapy regimen that is designed to prevent a relapse and usually continues for about 4 - 8 months.

Examples of consolidation regimens for patients at standard risk:

  • A limited number of courses of intermediate- or high-dose methotrexate
  • An anthracycline drug, such as daunorubicin (Cerubidine), used for reinduction followed by cyclophosphamide (Cytoxan, Neosar) 3 months after remission
  • Extended use of an asparaginase drug.

More intense regimens are used for patients at high-risk for relapse.


The last phase of treatment is maintenance (also called continuation therapy):

  • Maintenance therapy typically uses weekly administration of methotrexate (usually in oral form) and daily doses of mercaptopurine.
  • If CNS prophylaxis was not given before, it may be given now.
  • Vincristine and a corticosteroid drug (generally dexamethasone) may be added to standard maintenance therapy.

A maintenance regimen is usually less toxic and easier to tolerate than induction and consolidation. Maintenance treatment lasts for about 2 - 3 years for most patients with ALL. It is not clear if maintenance therapy benefits patients who have certain specific types of ALL, such as T-cell ALL or mature B-cell ALL (Burkitt leukemia).

Treatment After Relapse

Relapse is when cancer returns after remission. Most patients with ALL achieve remission after induction therapy, but in some patients the disease returns.

The following are factors that increase the risk for relapse after initial treatments:

  • Microscopic evidence of leukemia after 20 weeks of therapy (minimal disease)
  • Age over 30
  • A high white blood cell count at the time of diagnosis
  • Disease that has spread beyond the bone marrow to other organs
  • Certain genetic abnormalities, such as the presence of the Philadelphia chromosome or MLL gene translocations
  • Patients with high disease levels after 7 - 14 days of induction therapy
  • The need for 4 or more weeks of induction chemotherapy in order to achieve a first complete remission.

Treatment for relapse after a first remission may be standard chemotherapy or experimental drugs, or more aggressive treatments such as stem cell transplants.

The decision depends on a number of factors including how soon relapse occurs after treatment:

  • Children who relapse 3 or more years after achieving a first complete remission usually achieve a second remission with a second round of standard chemotherapy treatments.
  • Children who relapse within 6 months to 3 years following treatment may be able to achieve remission with a more aggressive course of chemotherapy.
  • Children who relapse less than 6 months following initial treatment, or while on chemotherapy have a lower chance for a second remission. In such cases, stem cell transplantation may be considered. Stem cell transplantation is especially considered for children who relapse with T-cell ALL.
  • Adult patients with ALL who experience a relapse following maintenance therapy are unlikely to be helped by additional chemotherapy alone. They are considered candidates for stem cell transplantation. Stem cell transplantation is also an option for adults, but not children, who have achieved a first remission.

Transplantation procedures are reserved for patients with high-risk disease who are unlikely to achieve remission with chemotherapy alone. Transplantation does not offer any additional advantages for patients at low or standard risk.

Chemotherapy Drugs Used After Relapse

Many different drugs are used to treat ALL relapses. These drugs include vincristine, asparaginase, anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine (ara-C), and epipodophyllotoxins (etoposide, teniposide). In 2012, the FDA approved Marqibo, a specially-formulated type of vincristine injection, for adults with Philadelphia chromosome-negative ALL. Other drugs for relapsed or refractory ALL include nelarabine (Arranon), for T-cell ALL, and clofarabine (Clolar). Corticosteroids, such as prednisone or dexamethasone, may also be used.

The most recently approved treatments for ALL are biologic drugs that are tyrosine kinase inhibitors (TKIs). Tyrosine kinase is a growth-stimulating protein. TKI drugs block the cell signals that trigger cancer growth. TKI drugs approved for adult patients with Philadelphia chromosome-positive (Ph+) ALL include:

  • Imatinib (Gleevec) is approved for adults with Ph+ ALL that has not responded to or has returned after treatment
  • Dasatinib (Sprycel) is approved for adult patients with Ph+ ALL who were not helped by imatinib or other treatments
  • Ponatinib (Iclusig) is approved for adults with Ph+ ALL that has not responded to prior treatment with another tyrosine kinase inhibitor drug such as imatinib or dasatinib



Stem cells that are made in the bone marrow are the early form of all blood cells in the body. They normally mature into red, white, or immune cells. To help the patient survive high dose chemotherapy needed to cure leukemia that has returned treatment, or not responded to treatment, a stem cell transplantation procedure may be used. Stem cell transplantation replaces blood stem cells that were lost during the initial chemotherapy treatment. The lost stem cells are replaced by transplanting them from a donor into the patient.

Types of Donors

The stem cells to be given to the person with leukemia can come from either the patient (autologous) or a donor(allogeneic):

  • Allogeneic transplant. In an allogeneic transplant, the stem cells are taken from another person or donor. The immune system of the person receiving the new cells will usually try to reject these new, foreign cells. The more similar genetically the donor cells are, however, the less likely the person receiving the cells will reject them. Allogeneic transplants that are from genetically matched sibling donors offer the best results in ALL. With new techniques, donor bone marrow from unrelated but immunologically similar donors is proving to work as well as those from matched siblings
  • Autologous transplant. If the marrow or blood cells used are the patient's own, the transplant is called autologous. Autologous transplants in patients with ALL are generally not beneficial, since there is some danger that the cells used may contain tumor cells and the cancer can regrow. Treatment advances that reduce this risk, however, may make autologous transplantation feasible in patients without family donors.

The Blood Stem Cell Collection Procedure

Sources of Cells. Stem cells can be obtained either from the donor’s:

  • Bone marrow (bone marrow transplantation)
  • Blood (peripheral blood stem cell transplantation)

The Transplant Procedure

  • The patient with ALL is given high-dose chemotherapy with or without radiation -- a treatment known as conditioning. The point is to inactivate the immune system and to kill any remaining leukemia cells.
  • A few days after treatment, the patient is rescued using the stored stem cells, which are administered through a vein. This may take several hours. Patients may experience fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
  • The patient is kept in a protected environment to minimize infection, and the patient usually needs blood cell replacement and nutritional support.

Side Effects and Complications

Stem-cell transplantation is a serious and complex procedure that can cause many short- and long-term side effects and complications. Early side effects of transplantation are similar to chemotherapy and include nausea, vomiting, fatigue, mouth sores, and loss of appetite. Bleeding because of reduced platelets is a high risk during the first four weeks and may require transfusions. Later side effects include fertility problems (if the ovaries are affected), thyroid gland problems (which can affect metabolism), lung damage (which can cause breathing problems) and bone damage.

Two of the most serious complications of transplantation are infection and graft-versus-host disease:

Infection resulting from a weakened immune system is the most common danger. The risk for infection is most critical during the first 6 weeks following the transplant, but it takes 6 - 12 months post-transplant for a patient’s immune system to fully recover. Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia and infections with germs that normally do not cause serious infections such as cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis jerovicii (a fungus) are among the most serious life-threatening infections.

It is very important that patients take precautions to avoid post-transplant infections. (See Home Management section of this report.)

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants.

Acute GVHD occurs in 30 - 50% of allogeneic transplants, usually within 25 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). The first sign of acute GVHD is a rash, which typically develops on the palms of hands and soles of feet and can then spread to the rest of the body. Other symptoms may include nausea, vomiting, stomach cramps, diarrhea, loss of appetite and jaundice (yellowing of skin and eyes). To prevent acute GVHD, doctors give patients immune-suppressing drugs such as steroids, methotrexate, cyclosporine, tacrolimus, and monoclonal antibodies.

Chronic GVHD can develop 70 - 400 days after the allogeneic transplant. Initial symptoms include those of acute GVHD. Skin, eyes, and mouth can become dry and irritated, and mouth sores may develop. Chronic GVHD can also sometimes affect the esophagus, gastrointestinal tract and liver. Bacterial infections and chronic low-grade fever are common. Chronic GVHD is treated with similar medicines as acute GVHD.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Home Management

A parent should call the doctor if the child has any symptoms that are out of the ordinary, including (but not limited) to:

  • Any fever of 101 °F or higher
  • Any signs of a flu or cold
  • Shortness of breath
  • Severe diarrhea
  • Blood in the urine or stools
  • Trouble urinating

Tracking Neutrophils. Parents should track their child's absolute neutrophil count. This measurement for the amount of white blood cells is an important gauge of a child's ability to fight infection.

  • Counts over 1,000 usually provide sufficient protection so that children can engage in normal activities, including school and other functions where they are exposed to other children.
  • If the count is between 500 - 1,000, the child should avoid large groups.
  • If it falls between 200 - 500, the child should stay at home and should see only healthy visitors who have washed their hands vigorously.
  • Neutrophil counts below 200 indicate that the child is at high risk for infection and should have no visitors.

Preventing Infection

It is very important to take precautions to prevent infection following chemotherapy or transplantation. Guidelines for infection prevention and control include:

  • Discuss with the doctor what vaccinations are needed and when. Children with ALL may need reimmunization. In general, it is best to have immunizations prior to chemotherapy and to avoid live virus vaccines during treatment,
  • Avoid crowds, especially during cold and flu season.
  • Be diligent about hand washing and make sure that visitors wash their hands. Alcohol-based handrubs are best.
  • Avoid eating raw fruits and vegetables. Poultry, meat, fish, eggs and other foods should be cooked thoroughly. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
  • Boil tap water before drinking it.
  • Dental hygiene is very important, including daily brushing and flossing. Use a soft toothbrush to prevent gum bleeding. Schedule regular visits with your dentist.
  • Do not sleep with pets. Avoid contact with pets' excrement.
  • Avoid fresh flowers and plants as they may carry mold. Do not garden.
  • Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
  • Report to the doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
  • Report to the ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.
  • Some of the drugs used for leukemia cause extreme sun sensitivity. Sunburn can cause skin infection. Children should wear sunblock and sun-protective clothing when going outside.



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  • Last Reviewed on 03/08/2013
  • Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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