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Some children with leukemia are critically ill when they are first diagnosed with leukemia. For example:
A shortage of normal white blood cells may lead to very serious infections.
Low levels of platelets or clotting factors in the blood can cause severe bleeding.
Not having enough red blood cells can lower the amount of oxygen getting to body tissues and put a tremendous strain on the heart.
These problems must often be addressed before treatment of the leukemia can begin. Antibiotics, blood growth factors, and transfusions of platelets and red blood cells may be given to treat or help prevent some of these conditions.
Surgery for childhood leukemia
Surgery has a very limited role in the treatment of childhood leukemia. Because leukemia cells spread throughout the bone marrow and to many other organs through the blood, it is not possible to cure this type of cancer by surgery. Aside from a possible lymph node biopsy, surgery rarely has any role even in the diagnosis, since a bone marrow aspirate and biopsy can usually diagnose leukemia.
Often before chemotherapy is about to start, surgery is needed to insert a small plastic tube, called a central venous catheter or venous access device (VAD), into a large blood vessel. The end of the tube stays just under the skin or sticks out in the chest area or upper arm. The VAD is left in place during treatment to give intravenous (IV) drugs such as chemotherapy and to take blood samples. This lowers the number of needle sticks needed during treatment. It is very important for parents to learn how to care for the catheter to keep it from getting infected.
In cases where a boy with leukemia has a relapse of the disease in a testicle, surgery may sometimes be done to remove the testicle (along with giving chemotherapy to treat the rest of the body).
Radiation therapy for childhood leukemia
Radiation therapy uses high-energy radiation to kill cancer cells. Radiation is sometimes used to try to prevent or treat the spread of leukemia to the brain or the testicles.
Radiation is also used (rarely) to treat a tumor that is compressing the trachea (windpipe). But chemotherapy is often used instead, as it may work more quickly.
Radiation to the whole body is often an important part of treatment before a bone marrow or peripheral blood stem cell transplant .
External beam radiation therapy, in which a machine delivers a beam of radiation to a specific part of the body, is the type of radiation used most often for childhood leukemia. Before treatment starts, the radiation team will take careful body measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless, but some younger children may need to be sedated to make sure they don't move during the treatment. Each treatment lasts only a few minutes, although the setup time – getting your child into place for treatment – usually takes longer.
Possible side effects of radiation
The possible short-term side effects of radiation therapy depend on where the radiation is aimed. Sunburn-like skin changes and hair loss in the treated area are possible. Radiation to the abdomen can sometimes cause nausea, vomiting, or diarrhea. For radiation that includes large parts of the body, the effects may include fatigue and an increased risk of infection.
Chemotherapy for childhood leukemia
Chemotherapy (chemo) is treatment with anti-cancer drugs that are given into a vein, into a muscle, into the cerebrospinal fluid (CSF), or taken by mouth as pills. Except when given into the CSF, these drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers such as leukemia.
The treatment of leukemia uses combinations of several anti-cancer drugs. Doctors give chemo in cycles, with each period of treatment followed by a rest period to allow the body time to recover. In general, treatment for acute myeloid leukemia (AML) uses higher doses of chemo over a shorter period of time, and acute lymphocytic leukemia (ALL) treatment uses lower doses of chemo over a longer period of time (usually 2 to 3 years).
Some of the drugs commonly used to treat childhood leukemia include:
Vincristine (Oncovin)
Daunorubicin, also known as daunomycin (Cerubidine)
Doxorubicin (Adriamycin)
Cytarabine, also known as cytosine arabinoside or ara-C (Cytosar)
L-asparaginase (Elspar), PEG-L-asparaginase (pegaspargase, Oncaspar)
Etoposide (VePesid, others)
Teniposide (Vumon)
6-mercaptopurine (Purinethol)
6-thioguanine
Methotrexate
Mitoxantrone
Cyclophosphamide (Cytoxan)
Prednisone (numerous brand names)
Dexamethasone (Decadron, others)
Children will probably get several of these drugs at different times during the course of treatment, but they do not get all of them.
Possible side effects of chemotherapy
Chemotherapy drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.
The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. These side effects may include:
Hair loss
Mouth sores
Loss of appetite
Diarrhea
Nausea and vomiting
Increased risk of infections (because of low white blood cell counts)
Bruising and bleeding easily (from low platelet counts)
Fatigue (caused by low red blood cell counts)
The problems with blood cell counts are often caused by the leukemia itself at first. They might get worse during the first part of treatment because of the chemotherapy, but they will probably improve as the normal cells recover and the leukemia cells are killed off.
The side effects listed above are usually short-term and go away when treatment is finished. There are often ways to reduce these side effects. For instance, drugs can be given along with the chemotherapy to help prevent or reduce nausea and vomiting. Other drugs known as growth factors can be given to help keep the blood cell counts higher.
Tumor lysis syndrome is another possible side effect of chemotherapy. It can be seen in patients who had large numbers of leukemia cells in the body before treatment. When chemo kills these cells, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which aren't able to get rid of all of these substances at once. Excess amounts of certain minerals may also affect the heart and nervous system. This can be prevented by making sure the child gets lots of fluids during treatment and by giving certain drugs, such as bicarbonate, allopurinol, and rasburicase, which help the body get rid of these substances.
Some chemo drugs can also have specific side effects that are not listed above. Be sure to ask your child's doctor or nurse about any specific side effects you should watch for and about what you can do to help reduce these side effects.
Chemotherapy given directly into the cerebrospinal fluid (CSF) around the brain and spinal cord can have its own side effects, although these are not common. Chemo may cause trouble thinking or even seizures in some children.
Targeted therapy for childhood leukemia
In recent years, new drugs that target specific parts of cancer cells have been developed. These targeted drugs work differently from standard chemotherapy drugs. They often have different (and less severe) side effects. Some of these drugs may be useful in certain cases of childhood leukemia.
For instance, drugs such as imatinib (Gleevec) and dasatinib (Sprycel) specifically attack cells that have the Philadelphia chromosome (a shortened chromosome 22 that results from a translocation with chromosome 9).
Nearly all children with chronic myeloid leukemia (CML) have this abnormal chromosome in their leukemia cells. These drugs are very effective at keeping the leukemia under control for long periods of time in most of these children, although it's not yet clear if the drugs can help cure CML.
A small portion of children with acute lymphocytic leukemia (ALL) also have leukemia cells with the Philadelphia chromosome. Studies are now being done to find out if these drugs can be combined with chemotherapy to get better outcomes. Early results from such studies have been promising.
These drugs are taken daily as pills. Possible side effects include diarrhea, nausea, muscle pain, fatigue, and skin rashes. These are generally mild. A common side effect is swelling around the eyes or in the hands or feet. Some studies suggest this fluid buildup may be caused by the drugs' effects on the heart. Other possible side effects include lower red blood cell and platelet counts at the start of treatment. These drugs may also slow a child's growth, especially if used before puberty.
High-dose chemotherapy and stem cell transplant for childhood leukemia
A stem cell transplant (SCT) can sometimes be used for children whose chances of being cured are poor with standard or even intensive chemotherapy. SCT lets doctors use even higher doses of chemotherapy than would normally be tolerated.
High-dose chemotherapy destroys the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems caused by low blood cell counts. A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy and, sometimes, radiation therapy. After treatment is finished, the child receives a transplant of blood-forming stem cells to restore the bone marrow.
Blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant [PBSCT] or an umbilical cord blood transplant) or from the bone marrow (for a bone marrow transplant, or BMT). Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCT and cord blood transplants.
Types of transplants
There are 2 main types of stem cell transplants: allogeneic and autologous. They differ in the source of the blood-forming stem cells.
Allogeneic stem cell transplant: For childhood leukemia, the blood-forming stem cells are generally donated from another person. This is called an allogeneic transplant, meaning the cells come from someone else. Allogeneic stem cell transplants are the type of transplant used for childhood leukemias.
The donor's tissue type (also known as the HLA type) should be almost identical to the patient's tissue type to help prevent the risk of major problems with the transplant. Tissue type is based on certain substances on the surface of cells in the body. These substances can cause the immune system to react against the cells. Therefore, the closer a tissue "match" is between the donor and the recipient, the better the chance the transplanted cells will "take" and begin making new blood cells.
Usually the donor is a brother or sister if they have the same tissue type as the patient. Rarely, it may be an HLA-matched, unrelated donor – a stranger who has volunteered to donate blood-forming stem cells. Sometimes umbilical cord stem cells are used. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the umbilical cord is cut. (This blood is rich in stem cells.) Whatever their source, the stem cells are then frozen and stored until they are needed for the transplant.
Autologous stem cell transplant: In an autologous transplant, the patient's own stem cells are removed from his or her bone marrow (bone marrow stem cells) or bloodstream (peripheral blood stem cells, PBSCs). They are frozen and stored while the child gets treatment (high-dose chemotherapy and/or radiation). A process called purging may be used to try to remove any leukemia cells in the samples. The stem cells are then reinfused into the child's blood after treatment.
This type of transplant is not used for childhood leukemia, because the risk that the leukemia will come back (relapse) after treatment is greater than with an allogeneic transplant. There are a couple of reasons for this. One concern is that there are leukemia cells in the child's blood and bone marrow, so there may be a risk of returning these leukemia cells to the child after treatment. Purging can reduce this risk, but it may not eliminate it completely. An allogeneic transplant may also be more effective than an autologous transplant because of the "graft versus leukemia" effect. When the donor immune cells are infused into the body as part of the transplant, they may recognize any remaining leukemia cells as being foreign to them and attack them. This effect doesn't happen with autologous stem cell transplants.
When stem cell transplant (SCT) might be used
SCT might be used for a child with ALL whose leukemia doesn’t respond well to initial treatment or relapses early after going into remission. It is less clear if SCT should be used for those children with ALL who relapse more than 6 months after finishing their initial chemotherapy. These children will often do well with another round of standard dose chemotherapy. SCT may also be recommended for children with some less common forms of ALL, such as those whose leukemias have the Philadelphia chromosome (translocation between chromosomes 9 and 22) or those with T-cell ALL that doesn't respond well to initial treatment.
Because AML relapses more often than ALL, many doctors recommend SCT for children with AML right after they have gone into remission, if the child has a brother or sister with the same tissue type who can donate stem cells for the transplant. This is especially true if there is a very high risk of relapse (as seen with some subtypes of AML or when there are certain chromosome changes in the cells). There is still some debate about which children with AML need this type of intensive treatment, but the cytogenetic traits of the AML may help doctors identify which children need a SCT right away and which ones can be treated with chemotherapy alone. If a child with AML relapses after his or her first round of standard chemotherapy, most doctors will recommend SCT as soon as the child goes into remission again.
In either case, it is important that the leukemia is in remission before getting a stem cell transplant. Otherwise, the leukemia is more likely to return.
SCT may also offer the best chance to cure some less common types of childhood leukemia, such as juvenile myelomonocytic leukemia (JMML) and CML. For CML, newer targeted therapies are likely to be used first for most children. These drugs are often very effective for extended periods of time, but they do not appear to cure CML, so a transplant may still be needed at some point.
How a stem cell transplant (SCT) is done
Typically, the child getting the stem cell transplant is admitted to the stem cell transplant unit of the hospital on the day before the treatment begins. He or she will usually stay in the hospital until after the chemo and the stem cells have been given, and until the stem cells have started making new blood cells again (see below).
Stem cells collected from a donor or the patient are carefully frozen and stored. The child then receives high-dose chemotherapy and sometimes radiation treatment to the entire body. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.) These treatments are meant to destroy any remaining leukemia cells. But they also kill the normal cells in the bone marrow.
After treatment, the frozen stem cells are thawed and given as a blood transfusion. The stem cells settle into the child's bone marrow over the next several days and start to grow and make new blood cells.
Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is later followed by new platelet production and new red blood cell production. In the meantime, the child is at high risk for serious infections because of a low white blood cell count, as well as bleeding because of a low platelet count. During this time, blood and platelet transfusions and treatment with IV antibiotics are often used to help prevent or treat infections or bleeding problems.
Because of the high risk of serious infections right after treatment, patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until part of their white blood cell count (known as the absolute neutrophil count, or ANC) rises above 500. They may be able to leave the hospital when their ANC is near 1,000.
The child is then seen in an outpatient clinic almost every day for several weeks. Because platelet counts take longer to return to a safe level, they may get platelet transfusions as an outpatient. Patients may make regular visits to the outpatient clinic for about 6 months, after which time their care may be continued by their regular doctors.
Practical points
The stem cell transplant procedure is a complex treatment that can cause life-threatening side effects. If the doctors think your child may benefit from a transplant, the best place to have this done is at a nationally recognized cancer center where the staff has experience with the procedure and with managing the recovery period.
A stem cell transplant often requires a long hospital stay and can be very expensive (often costing well over $100,000). Because the procedure is so expensive, you should be sure to get a written approval from your insurer before treatment if it is recommended for your child. Even if the transplant is covered by your insurance, your co-pays or other costs could easily amount to many thousands of dollars. It is important to find out what your insurer will cover before the transplant to get an idea of what you might have to pay.
Possible side effects of stem cell transplants (SCT)
The possible side effects from SCT are generally divided into early and long-term effects.
Short-term side effects
The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy , and can be severe. They are caused by damage to the bone marrow and other quickly dividing tissues of the body and can include:
Low blood cell counts (with fatigue and an increased risk of infection and bleeding)
Nausea and vomiting
Loss of appetite
Mouth sores
Diarrhea
Hair loss
One of the most common and serious short-term effects is the increased risk of serious infections. Antibiotics are often given to try to prevent this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.
Long-term side effects
Some complications and side effects can persist for a long time or may not occur until months or years after the transplant. These can include:
Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants.
Radiation damage to the lungs
Problems with the thyroid or other hormone-making glands
Problems with fertility
Damage to bones or problems with bone growth
Development of another cancer (including leukemia) years later
Graft-versus-host disease is one of the most serious complications of allogeneic (donor) stem cell transplants. This happens when the donor immune system cells attack tissues of the patient's skin, liver, and digestive tract.
The areas most often affected include the skin, liver, and digestive tract, but other areas may be affected as well. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. In severe cases, GVHD can be life-threatening. Drugs that weaken the immune system are often given as a part of the transplant to try to prevent GVHD, although they may have their own side effects.
The most common symptoms of GVHD are severe skin rashes and severe diarrhea. If the liver is affected, the damage can lead to jaundice (yellowing of the skin and eyes) or even liver failure. GVHD can also cause lung damage, leading to problems breathing. The patient may feel weak, become tired easily, and have nausea, dry mouth, muscle aches.
On the good side, graft-versus-host disease can lead to "graft-versus-leukemia" activity. Any leukemia cells remaining after the chemotherapy and radiation therapy may be killed by the donor immune cells.
Treatment of children with acute lymphocytic leukemia
The main treatment for children with acute lymphocytic leukemia (ALL) is chemotherapy, which is usually divided into 3 phases:
Induction
Consolidation (also called intensification)
Maintenance
When leukemia is diagnosed, there are usually about 100 billion leukemia cells in the body. Killing 99.9% of these leukemia cells during the 1-month induction treatment is enough to achieve a remission, but it still leaves about 100 million leukemia cells in the body. These also must be destroyed. An intensive 1- to 2-month program of consolidation treatment and about 2 years of maintenance chemotherapy helps destroy the remaining cancer cells.
As mentioned earlier, children with ALL are typically divided into standard-risk, high-risk, or very high-risk groups to make sure that the correct types and doses of drugs are given. Treatment may be more or less intensive, depending on the risk group.
Induction
The goal of induction chemotherapy is to achieve a remission. This means that leukemia cells are no longer found in bone marrow samples, the normal marrow cells return, and the blood counts become normal. (A remission is not necessarily a cure.)
More than 95% of children with ALL enter remission after 1 month of treatment. This first month of treatment is quite intensive and requires frequent visits to the doctor. Your child may spend some or much of this time in the hospital, because serious infections or other complications can occur. It is very important to take all medicines prescribed. Sometimes complications can be serious enough to be life-threatening, but with advances in supportive care (nursing care, nutrition, antibiotics, red blood cell and platelet transfusions as needed, etc.) in recent years, these are much less common than in the past.
Children with standard-risk ALL often receive 3 drugs for the first month of treatment. These include the chemotherapy drugs L-asparaginase and vincristine, and a steroid (usually dexamethasone). A fourth drug in the anthracycline class (daunorubicin is the one most often used) is typically added for high-risk children. Other drugs that may be given early are methotrexate and/or 6-mercaptopurine.
Intrathecal chemotherapy: All children also need to get chemotherapy into the cerebrospinal fluid (CSF) to kill any leukemia cells that may have spread to the brain and spinal cord. This treatment, known as intrathecal chemotherapy, is given through a lumbar puncture (spinal tap). It is usually given twice (more often if the leukemia is high risk) during the first month and 4 to 6 times during the next 1 or 2 months. It is then repeated less often during the rest of consolidation and maintenance. Usually, methotrexate is used for intrathecal chemotherapy. Hydrocortisone (a steroid) and cytarabine (ara-C) may be added, particularly in high-risk children.
Along with intrathecal therapy, some high-risk patients (for example, those with T-cell ALL) and those with high numbers of leukemia cells detected in their CSF when the leukemia is diagnosed may be given radiation therapy to the brain. This was more common in the past, but recent studies have found that many children even with high-risk ALL may not need radiation therapy if they are given more intensive chemotherapy. Doctors try to avoid giving radiation to the brain if possible, especially in younger children, because no matter how low the dose is kept, it can cause problems with thinking and growth and development.
A possible side effect of intrathecal chemotherapy is seizures during treatment, which happen in a small portion of children. Children who develop seizures are treated with drugs to prevent them.
Consolidation (intensification)
The next, and usually more intense, consolidation phase of chemotherapy typically lasts about 1 to 2 months. This phase reduces the number of leukemia cells still in the body. Several chemo drugs are combined to help prevent the remaining leukemia cells from developing resistance. Intrathecal therapy (as described above) is continued at this time.
Children with standard-risk ALL are usually treated with drugs such as methotrexate and 6-mercaptopurine or 6-thioguanine, but regimens may differ among cancer centers. Vincristine, L-asparaginase, and/or prednisone may also be added.
Children with high-risk leukemia generally receive a more intense regimen of chemotherapy. Extra drugs such as L-asparaginase, doxorubicin (Adriamycin), etoposide, cyclophosphamide, and cytarabine (ara-C) are often used, and dexamethasone is substituted for prednisone. There may be a second round of intense chemotherapy with the same drugs.
Some children, such as those with Philadelphia chromosome-positive ALL, may benefit from the addition of a targeted drug such as imatinib (Gleevec) or from a stem cell transplant at this time.
Maintenance
If the leukemia remains in remission after induction and consolidation, maintenance therapy can begin. Most treatment plans use methotrexate and 6-mercaptopurine, given as pills, often along with vincristine, which is given intravenously, and a steroid (prednisone or dexamethasone). These latter 2 drugs are given for brief periods every 4 to 8 weeks. Other drugs may be added depending on the type of ALL and the risk of recurrence.
During the first few months of maintenance, most treatments include 1 or 2 repeat intensified treatments similar to the initial induction. These 4-week intensifications are called re-induction or delayed intensification.
Some leukemia patients at higher risk may receive more intensive maintenance chemotherapy and intrathecal therapy.
The total duration of therapy (induction, consolidation, and maintenance) for most ALL treatment plans is 2 to 3 years. Because boys are at higher risk for relapse than girls, many doctors favor giving them several more months of treatment.
Treatment of residual disease
These treatment plans may change if the leukemia doesn't go into remission during induction or consolidation. The doctor will probably check the child's bone marrow soon after treatment starts to see if the leukemia is going away. If not, treatment may be intensified or prolonged. If the leukemia seems to have gone away by standard lab tests, the doctor may do more sensitive tests to look for small numbers of leukemia cells that may remain. If any are found, then chemotherapy again may be intensified or prolonged.
Treatment of recurrent ALL
If the ALL recurs (comes back) at some point during or after treatment, the child will most likely be treated again with chemotherapy. Much of the treatment strategy depends on how soon the leukemia returns after the first treatment. If the relapse occurs after a long time interval, the same drugs may still be effective, so the same or similar treatment may be used to try to get a second remission. If the time interval is shorter, more aggressive chemotherapy with other drugs may be needed.
The most commonly used chemo drugs are vincristine, L-asparaginase, anthracyclines (doxorubicin, daunorubicin, mitoxantrone), cyclophosphamide, cytarabine (ara-C), and epipodophyllotoxins (etoposide, teniposide). The child will also receive a steroid (prednisone or dexamethasone). Intrathecal chemotherapy will also be given.
For children whose leukemia comes back within 6 months of starting treatment or for children with T-cell ALL who relapse, a stem cell transplant may be considered, especially if there is a brother or sister who is a good tissue type match. Stem cell transplants may also be used for other children who relapse after a second course of chemotherapy.
Some children have an extramedullary relapse, meaning that leukemia cells are found in one part of the body (such as the spinal fluid or the testicles) but are not detectable in the bone marrow. In addition to intensive chemotherapy as described above, children with spread to the spinal fluid may get more intense intrathecal chemotherapy, sometimes with radiation to the brain and spinal cord (if that area had not been already treated with radiation). Boys with relapse in a testicle may get radiation to the area, and in some cases may have the affected testicle removed by surgery.
Philadelphia chromosome-type ALL
For children with certain types of ALL, such as those with the Philadelphia chromosome or other high-risk genetic changes, standard chemotherapy for ALL (as outlined above) may not be as effective. A stem cell transplant may be advised if induction treatment yields a remission and a suitable stem cell donor is available.
Newer, targeted drugs such as imatinib (Gleevec) and dasatinib (Sprycel) are designed to kill leukemia cells that contain the Philadelphia chromosome. These drugs are taken as pills and seem to have limited side effects. Studies are now looking at whether adding these drugs to chemotherapy can help improve outcomes. Early study results have been promising so far.
Treatment of children with acute promyelocytic leukemia (APL)
Treatment of the M3 subtype of AML (acute promyelocytic leukemia, or APL) differs from usual AML treatment. The leukemia usually responds well to this treatment.
Induction
Many children with APL have blood-clotting problems at the time APL is diagnosed, which can cause serious problems during early treatment. Because of this, children with APL must be treated carefully and are often given an anticoagulant ("blood thinner") to help prevent or treat this.
Along with chemotherapy, children with APL receive a non-chemotherapy drug similar to vitamin A called all-trans retinoic acid (ATRA). A remission can often be induced with ATRA alone, but combining it with chemotherapy (usually daunorubicin and cytarabine) gives better long-term results. APL rarely spreads to the brain or spinal cord, so intrathecal chemotherapy is usually not needed.
Along with the possible side effects from the chemotherapy drugs, ATRA can cause a problem called retinoic acid syndrome. This can include breathing problems from fluid buildup in the lungs, low blood pressure, kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the ATRA for a while and giving a steroid such as dexamethasone.
Consolidation (intensification)
This is usually similar to induction, using both ATRA and chemotherapy (usually daunorubicin). Because of the success of this treatment, a stem cell transplant is not usually advised as long as the leukemia stays in remission.
Maintenance
Children with APL may receive maintenance therapy with ATRA (often with the chemo drugs methotrexate and 6-mercaptopurine) for about a year.
Relapsed APL
If the leukemia comes back after treatment, most cases can be put into a second remission. Arsenic trioxide is a drug that is very effective in this setting, although it can sometimes cause problems with heart rhythms. Children getting this drug need to have their blood mineral levels watched closely. ATRA plus chemotherapy may be another option. A stem cell transplant may be considered once a second remission is achieved.
Treatment of children with juvenile myelomonocytic leukemia (JMML)
JMML is fairly rare, so it has been hard to study, and there is no standard chemotherapy treatment for this leukemia. An allogeneic stem cell transplant is the treatment of choice when possible, as it offers the best chance to cure JMML. About half of the children with JMML who get a stem cell transplant are still free of leukemia after several years. Sometimes, even if the leukemia recurs, a second stem cell transplant can be helpful.
Because JMML is hard to treat with current chemo drugs, taking part in a clinical trial looking at newer drugs may be a good option for children who cannot get a stem cell transplant.
Treatment of children with chronic myelogenous leukemia (CML)
This leukemia is rare in children, but it does occur. Treatment in children is similar to treatment in adults.
Targeted drugs, such as imatinib (Gleevec) and dasatinib (Sprycel), attack cells with the Philadelphia chromosome, which is the key genetic abnormality in CML. These drugs are usually very effective at controlling CML, often for long periods of time and with less severe side effects than chemotherapy drugs. However, these drugs do not seem to cure CML when used by themselves, and they must be taken every day.
Imatinib is usually the drug tried first. If it does not work or if it becomes less effective over time, another drug may be tried. If targeted drugs are no longer helpful, high-dose chemotherapy with a stem cell transplant offers the best chance for a cure. Doctors are now studying whether adding targeted drugs to stem cell transplant regimens can help increase cure rates.
What happens after treatment for childhood leukemia?
Following treatment for childhood leukemia, the main concerns for most families are the immediate and long-term effects of the leukemia and its treatment, and concerns about possible recurrence of the cancer.
It is certainly understandable to want to put the leukemia and its treatment behind you and to get back to a life that doesn't revolve around the cancer. But it's important to realize that follow-up care is a central part of this process that offers your child the best chance for recovery and long-term survival.
Follow-up exams
For several years after treatment, regular follow-up exams will be very important. The doctors will continue to watch for possible signs of leukemia, as well as for short-term and long-term side effects of treatment.
Checkups typically include careful physical exams, lab tests, and sometimes, imaging tests. These checkups will usually occur monthly during the first year, and then less often for at least 5 years after therapy. After that time, most children see their doctor at least yearly for a checkup.
If leukemia does recur, it is most often while the child is still being treated or within a year or so after finishing treatment. It is unusual for ALL or AML to return if there are no signs of the disease within the next 2 years.
A benefit of follow-up care is that it gives you a chance to discuss questions and concerns that arise during and after your child's recovery. For example, almost any cancer treatment can have side effects. Some may last for a few weeks to several months, but others can be permanent. It is important to report any new symptoms to the doctor right away, so that the cause can be found and treated, if needed.
Long-term effects of cancer treatment of childhood leukemia
Because of major advances in treatment, more children treated for cancer (including leukemia) are now living into adulthood. With childhood cancer survivors living longer, their health as they get older has come more into focus in recent years.
Just as the treatment of childhood cancer requires a very specialized approach, so does follow-up and monitoring for late effects of treatment. Careful follow-up after cancer treatment is very important.
Childhood leukemia survivors are at risk, to some degree, for several possible late effects of their cancer treatment. This risk depends on a number of factors, such as the type of leukemia, the type of treatments they received, dosages of cancer treatment, and age at the time of treatment.
Children who have been treated for leukemia are at higher risk of developing other cancers later in life. One of the most serious possible side effects of acute lymphocytic leukemia (ALL) therapy is a small risk of getting acute myelogenous leukemia (AML) later on. This occurs in about 5% of patients after they have received chemotherapy drugs called epipodophyllotoxins (etoposide, teniposide) or alkylating agents (cyclophosphamide, chlorambucil). Of course, the risk of getting these second cancers must be balanced against the obvious benefit of treating a life-threatening disease such as leukemia with chemotherapy.
Late effects may also include heart or lung problems after receiving certain chemotherapy drugs or radiation therapy to these parts of the body. The risks of heart disease and stroke later in life are much higher among those treated for ALL as children, so careful follow-up is very important. ALL survivors are also more likely to be overweight and to have high blood pressure, which can contribute to these problems.
Treatment that includes radiation therapy to the brain may affect learning ability in some children, as might some types of chemotherapy. Because of this, doctors try to limit treatments that could affect the brain (including radiation) as much as possible.
Survivors of childhood leukemia often suffer from emotional or psychological problems. They also may have some problems with normal functioning and schoolwork. These can often be helped with support and encouragement.
Some cancer treatments may affect a child's growth, and they may end up a bit shorter as adults. This is especially true after stem cell transplants. This can be helped by the treating survivors with growth hormone, if needed.
Cancer treatment may also affect sexual development and ability to have children in some cases.
Bone damage or osteoporosis (thinning of the bones) may result from the use of prednisone, dexamethasone, or other steroid drugs.
There may be other possible complications from chemotherapy as well. Your child's doctor should carefully review any possible problems with you before your child starts treatment.
Long-term follow-up guidelines
To help increase awareness of late effects and improve follow-up care of childhood cancer survivors throughout their lives, the Children's Oncology Group (COG) has developed long-term follow-up guidelines for survivors of childhood cancers. These guidelines can help you know what to watch for, what type of screening should be done, and how late effects may be treated.
It is very important to discuss possible long-term complications with your child's health care team, and to make sure there is a plan in place to watch for these problems and treat them, if needed.
What`s new in childhood leukemia research and treatment?
Researchers are now studying the causes, diagnosis, supportive care, and treatment of leukemia at many medical centers, university hospitals, and other institutions.
Genetics
As noted in the section "Do we know what causes childhood leukemia?" scientists are making progress in understanding how changes in DNA can cause bone marrow stem cells to develop into leukemia cells. Understanding the gene changes (such as translocations or extra chromosomes) that often occur in leukemia gives us insight into why these cells may grow out of control, and why they do not develop into normal, mature cells. Doctors are now looking to use these changes to help them determine a child's outlook and whether they should receive more or less intensive treatment.
This progress has already led to vastly improved and highly sensitive tests for detecting leukemia in blood or bone marrow samples. The polymerase chain reaction (PCR) test, for example, can identify very small numbers of leukemia cells based on their gene translocations or rearrangements. This test is useful in determining how completely the leukemia has been destroyed by treatment, and whether a relapse will occur if further treatment is not given.
Clinical trials
Most children are treated for leukemia at major medical centers, where treatment often involves taking part in clinical trials to provide the most up-to-date care.
