Some children diagnosed with CML have extremely high WBC counts at diagnosis. Large numbers of WBCs can cause the blood to become thick and viscous, sometimes leading to problems such as tumor lysis syndrome (when large amounts of cancerous cells are rapidly killed by therapy, which can lead to kidney failure) or blockages in blood vessels in the brain. Therefore, children with extremely high WBC counts at diagnosis (>200,000) may be treated with the following:

• The chemotherapy drugs hydroxyurea or allopurinol.
• A process called leukapheresis, in which blood is taken from body, put through a machine to remove the WBCs, and then transfused back into the child’s body.

When we took Madison to the hospital after we learned she had a WBC count of over 500,000, they did a bone marrow aspiration that confirmed it was CML. The first thing they did was leukapheresis, which is a way to take blood out of the body, remove white cells, and put the blood back in the body. This is to reduce the number of white blood cells before giving treatment and to protect organs from side effects. She had both a femoral line in her groin and a line in her arm, so they took blood out of one, ran it through the machine to take out the white cells, then put the blood back in through the other line.

In the past, children and teens with CML were first treated with hydroxyurea, followed by interferon-alpha (sometimes with cytosine arabinoside added) and then an allogeneic stem cell transplant if a matched donor was available. But, the development of imatinib (Gleevec®) has revolutionized treatment for CML. Use of this drug has resulted in 80 to 90% of children diagnosed in the chronic phase entering and remaining in remission for many years.

When my 7-year-old daughter was diagnosed with CML, they did leukapheresis, gave her two units of red blood cells, then started her on Gleevec® (300 mg) immediately. Within two weeks, her WBC count was cut in half. At 11 years old, they increased her dose to 450 mg a day. She had many of the usual side effects—her growth was slowed (went from 90th percentile in weight and height to the 25th) and she had some joint pain. Within four months of diagnosis, she was in a major molecular response.

Imatinib and other TKIs work differently than chemotherapy, because they specifically target the BCR-ABL protein and do not damage healthy cells. These drugs are usually very good at controlling CML for long periods of time and with far less severe side effects than chemotherapy drugs. However, they do not cure CML when used alone, and they must be taken every day. More information is available in Chapter 13, Chemotherapy and Other Medications. To monitor the effectiveness of the medication, a very sensitive test called PCR (polymerase chain reaction) is done periodically to measure the amount of BCR-ABL present. It is done on blood or bone marrow samples and can detect very small amounts of BCR-ABL.

Our son was one of the first kids put on Gleevec® at our children’s hospital. It began to work right away, cutting his WBC count in half within a couple of weeks. He had several difficult side effects, such as foot and leg pain, a rash on his face, as well as nausea from the pills. We didn’t feel heard about these side effects; his doctors thought the symptoms were unrelated because most adult patients do really well with these “easy” pills. We are members of a pediatric CML online support group, and we learned that these effects are quite common. For some kids, these side effects subside after a few months. But, seven years into treatment, our son still has considerable fatigue, nausea, and if he’s been on his feet all day, the area behind his knees becomes painful.

Currently, imatinib is the primary treatment used for children diagnosed with CML in the chronic phase. Doctors do not yet know when to stop treatment of children with imatinib; currently children remain on the drug indefinitely. If the drug stops working (or never worked well), the dose is increased or one of the second-line drugs from the same family (dasatinib, nilotinib, bosutinib, or ponatinib) is used. However, the long-term effects of these second-line targeted drugs are not known.

Treatment options for children or teens in the accelerated phase or in blast crisis are designed to eliminate as much disease as possible before doing a stem cell transplant (SCT). Treatments may include a targeted drug such as imatinib for accelerated phase, or a high-dose combination chemotherapy plus a targeted drug for blast crisis. For these children, treatment with chemotherapy and TKIs is most often followed by an SCT.

In the past, surgical removal of the spleen was part of CML treatment. This is no longer done because it significantly increases the risk of survivors developing life-threatening infections later in life. Radiation of the spleen is sometimes used if treatment with imatinib does not reduce the size of a very enlarged spleen.

At the present time, a SCT is the only known cure for children and teens with CML. But transplants can have severe and even life-threatening complications, and the short- and long-term toxicities are well known. Because targeted treatments (e.g., imatinib, dasatinib) can keep the disease at bay for years, the best use and timing of SCT for children with CML in the chronic phase is not known. SCT is generally reserved for children who do not respond well to targeted treatments, are unable to tolerate these drugs, or relapse on targeted therapy.

Families of kids with CML live with a cloud of uncertainty over our heads. It isn’t known how long Gleevec® and related medications work for kids. At the beginning, Tommy had bone marrow aspirations every three months, and his PCR results stayed low, but never reached zero. One year it went up quite a bit, and our team suggested that he take his Make-a-Wish® trip because he might need a stem cell transplant. But, luckily, they decided to watch and wait and the PCR result went back down and stayed there. His numbers fluctuate a bit but overall have remained stable. His sister is a perfect match should we ever have to go that route.

If targeted drugs are no longer working, high-dose chemotherapy with a SCT is sometimes suggested, especially if a matched donor is available. The types of transplant used to treat children with CML are:

• Syngeneic (from an identical twin)
• Allogeneic (from an HLA-identical sibling or a matched unrelated donor)
• Umbilical cord blood

Children and teens who receive imatinib before transplant have higher cure rates. Although the effect has not yet been studied, most transplant doctors give children imatinib for a year after transplant. More information about SCTs is available in Chapter 16, Stem Cell Transplantation.

My daughter has never complained about her cancer and treatment. She never asked, “Why me?” I have tried hard not to let this define who she is. She is smart, demure, and quiet, and she lives her life like every other child. I didn’t put her in a bubble and it was a good decision. It has changed who I am, however. I know who the people around me really are. People I was close to disappeared, but people I didn’t know well stepped up and filled the gap. My children had a good life before the diagnosis of CML, but they have a great life now. We try hard to live life as normally as possible. When we have to go to the hospital for tests, we make a weekend of it. We go to a nice hotel, a Broadway show, and a fancy dinner. Girls’ night out!