High-dose chemotherapy and stem cell transplant for childhood leukemia

Stem cell transplant (SCT) can sometimes be used for children whose chances of cure are poor with standard or even intense chemo. SCT allows doctors to use very high doses of chemo. The high doses of these drugs destroy the bone marrow, which keeps new blood cells from being made. This poses a threat to the child's life. But after treatment is finished, the child gets a transplant of blood-forming stem cells to replace the bone marrow. Stem cells are very early cells that are able to make new blood cells.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. The difference is the source of the blood-forming stem cells.

Allogeneic SCT: For childhood leukemia, the blood-forming stem cells come from the blood or bone marrow of another person. This is called an allogeneic stem cell transplant.

Usually the donor is a brother or sister but, rarely, the donor could be an unrelated volunteer. Stored cells from umbilical cord blood have also been used for unrelated donor transplants. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the cord is cut.

Autologous SCT: In an autologous stem cell transplant, the patient's own stem cells are removed from his or her bone marrow or bloodstream. They are frozen until after treatment with chemo and/or radiation and then given back to the patient.

This procedure is not used for childhood leukemia, for a couple of reasons. One concern is that there may be leukemia cells among the stem cells, which could be given back to the child after treatment. And leukemia has more of a chance to relapse if the child's own stem cells are used.

When SCT may be used

SCT may be used for children with ALL whose leukemia doesn’t respond well to the first treatment or comes back early after going into remission. It is less clear whether it should be used if more than 6 months has passed since the chemo was given. These children will often do well with another round of standard chemo. SCT may also be advised for children with some less common forms of ALL.

Because AML comes back more often, some doctors recommend SCT for some children with AML right after they have gone into remission, especially if the child has a brother or sister who can donate cells. If the cancer comes back after the first round of chemo, then most doctors will suggest SCT as soon as the child goes into remission again.

In any case, it is important that the leukemia is in remission before the transplant. Otherwise, it 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.

What SCT involves

Here is how the SCT process works: Stem cells are collected from either the bone marrow or from the bloodstream. The cells are frozen and stored.

The child is admitted to the hospital and is given very high doses of chemo (and sometimes radiation) to kill the cancer cells. As a result, all of the normal cells in the bone marrow are also killed. After treatment, the stored stem cells are thawed and given to the child as a blood transfusion. The stem cells settle in the child's bone marrow over the next few days and start to grow and make new blood cells. For the next few weeks the child is at high risk for serious infections (because of low white blood cell counts), as well as bleeding (because of low platelet counts). Transfusions and antibiotics are often used to prevent or treat these problems.

Patients most often stay in the hospital until a certain white blood cell count (called the ANC) is near 1,000. The child is then seen in an outpatient clinic almost every day for several weeks. Patients may make regular visits to the outpatient clinic for about 6 months, after which time their care may be given by their regular doctors.

Stem cell transplant is a complex treatment that can cause life-threatening side effects. If the doctors think that a child with leukemia might be helped by this treatment, it is important that it be done at a hospital where the staff has a lot or experience with the procedure.

Stem cell transplant can also be very expensive (often costing well over $100,000) and often involves a long hospital stay. Because it is so costly, parents should be sure to get a written approval from their insurer if their child is to have this treatment. 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.

Side effects of SCT

Side effects from a stem cell transplant can be divided into early and long-term effects.

Short-term side effects: Early side effects are about the same as those of any other type of high-dose chemo (low blood cell counts, mouth sores, nausea, vomiting, diarrhea, hair loss, etc.) and can be severe. These side effects are caused by damage to the bone marrow and other tissues that divide quickly.

One of the most common and serious short-term effects is the increased risk of severe infection. Antibiotics are often given to try to prevent this. Other side effects, like low red blood cell and platelet counts, may mean that the patient will need transfusions or other treatments.

Long-term side effects: Some side effects can go on for a long time. Sometimes they don't show up until months or even years after the transplant. Long-term side effects could include the following:

• Graft-versus-host disease (see below)
• 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 (GVHD) is a major concern of an allogeneic (donor) stem cell transplant. It happens when the immune system of the patient is taken over by that of the donor. The donor immune system then begins to attack the patient's other tissues and organs.

Symptoms can include severe skin rashes with itching and severe diarrhea. The liver and lungs may also be damaged. The patient may also become tired and have aching muscles. If severe enough, the disease can be fatal. Drugs that weaken the immune system are often given to try to keep GVHD under control.

To learn more about stem cell transplants, see our article Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants). You can find out more about long-term effects in the section, “Long-term effects of treatment for childhood leukemia.”