Treatment for AML can be broadly divided into three main categories: treatment for children with APL, treatment for children with Down syndrome and AML, and treatment for the other types of AML. These are discussed separately because treatment is very different for these three groups of children and teens. Children are treated in cycles of treatment (called phases) with names such as induction, intensification, consolidation, or continuation. Depending on risk level, some phases are given more than once. Most children with AML enter remission (defined as less than 5% blasts in the bone marrow). However, treatment is still needed to kill any remaining cancer cells.

Children with acute promyelocytic leukemia (APL)

Treatment for children with APL has improved considerably in the last two decades because APL cancer cells are very sensitive to the chemotherapy drugs ATRA (all-trans retinoic acid) and arsenic trioxide. Studies have shown that adding arsenic to the treatment plan allows the use of certain chemotherapy drugs to be decreased, which reduces the chance of some types of late effects. The length of treatment has also decreased from 30 months to 8 months. The current standard treatment is based on risk level:

• Standard risk (WBC count less than 10,000/μL at diagnosis)
• High risk (WBC count 10,000/μL or higher at diagnosis)

Standard risk. Current treatment for all children with standard-risk APL starts with a 28-day induction phase. During this phase, children are given ATRA and arsenic trioxide. If the WBC count goes above 10,000 then hydroxyurea and dexamethasone are added. At the end of induction, a bone marrow test is done to check for minimum residual disease (MRD). Children who have MRD of 0.01 or higher on day 29 require more intensive treatment, which may involve an additional cycle of chemotherapy (mitoxantrone, cytarabine, and ATRA).

Almost all children with APL enter remission. However, treatment is still needed to kill any remaining cancer cells. The consolidation phase of therapy for children at standard risk of relapse usually includes cycles of ATRA and arsenic trioxide (total of 28 weeks). There is no maintenance phase. In addition, a bone marrow aspiration is done during consolidation to check for a molecular remission (when disease can no longer be detected in the bone marrow).

When Aidan was admitted, they did a lot of tests including a bone marrow aspiration. They didn’t do a spinal tap then because APL was a possible diagnosis, and kids with APL tend to bleed a lot. APL is very rare so our oncologist, who had never treated a child with APL, talked to the whole treatment team and other experts across the country to decide on a treatment. Because Aidan’s WBC was low and he had no CNS disease, he was considered a low-risk patient. On Day 29, he was in remission but his MRD was positive. After induction, he had eight months of treatment that included seven cycles (two weeks on/two weeks off) of ATRA and four cycles of arsenic (four weeks on/four weeks off). Because this treatment can damage the heart, he had echoes and EKGs every month for the first year. He finished treatment two years ago, and is in remission, feeling great, and with no heart damage (although he goes for echoes and EKGs yearly).

High risk. Current treatment for all children with high-risk APL includes a 28-day induction phase of ATRA, arsenic trioxide, IV dexamethasone, and idarubicin. Consolidation therapy for children at high risk of relapse usually includes cycles of ATRA and arsenic trioxide (total of 28 weeks). There is no maintenance phase. In addition, a bone marrow aspiration is done during consolidation to check for a molecular remission (when disease can no longer be detected in the bone marrow).

CNS treatment. Children with APL only need treatment to the brain when they have a bleed in the brain or disease in the CNS at diagnosis. Children with a bleed in their brain are given triple intrathecal therapy (methotrexate, hydrocortisone, and cytarabine) on day 29 of induction and six more doses during consolidation. Children with CNS disease receive between four and six doses of intrathecal triple therapy during induction and another six doses during consolidation. In addition, children with CNS disease are given leucovorin 24 hours after each intrathecal treatment.

Children with Down syndrome

Children with Down syndrome have a higher risk of developing AML than children without Down syndrome. But, most children with Down syndrome who develop AML have a favorable prognosis and a low relapse rate.

About 10% of infants with Down syndrome develop a disorder called transient leukemia or transient myeloproliferative disorder (TMD). This disorder usually disappears in a few months without treatment (called spontaneous remission). However, while children have this disorder, life-threatening symptoms can occur, including:

• Increased size of internal organs
• Liver damage
• Abnormal amounts of fluid in the body
• Increased bleeding due to a clotting problem
• High WBC count

Children who develop these symptoms are sometimes treated with leukopheresis (taking the WBCs out of the blood) and low-dose cytarabine. Children with Down syndrome who had TMD when they were infants have a 10 to 30% chance of developing AML in the first three years of life.

Our daughter has Down syndrome and we aren’t sure if she had transient myeloproliferative disorder [TMD] or not. When she was 1.5 months old she became really pale and had trouble breathing. They discovered a malrotation of her intestines in addition to the heart abnormality that we already knew about. Her blood work showed low platelets (80,000) and low hemoglobin (4.4). They put in a G tube [permanent feeding tube] to replace the temporary nasogastric tube that she had been using because of trouble breathing and eating relating to her heart condition. They also did a bone marrow biopsy but did not find leukemia. They continued monthly blood checks after her open heart surgery at 3.5 months, and her counts were normal. One year later she was diagnosed with AML. In retrospect, they think she might have had TMD.

Children with Down syndrome are very sensitive to some chemotherapy drugs commonly used to treat AML. Recent clinical trials have reduced the intensity of treatment (e.g., reduced cytarabine dose and eliminated etoposide and dexamethasone) while maintaining survival rates. Daunorubicin dosage has also been decreased due to concerns about late effects to the heart. Thus, current standard treatment is less toxic than what was used in the past.

Our daughter was diagnosed with AML at 14 months old and she is now five years old. They did not mention a clinical trial, and she was treated with the usual AML drugs but at lower doses because she has Down syndrome. Kids with Down syndrome are very responsive to chemo drugs, and we ended up spending almost the entire six months of treatment inpatient because her absolute neutrophil count [ANC] rarely went above 500, which is expected with AML treatment. She went into remission after the first treatment cycle, but we still had to complete the entire six rounds to make sure all of the leukemia cells were completely wiped out. It was hard—she had severe sepsis after the third course, and she relied on a feeding tube the whole time. But, I was able to pump and feed her breast milk throughout treatment.

Most children younger than age four start treatment with an induction phase of cytarabine, daunorubicin, and thioguanine. Minimum residual disease (MRD) is assessed at the end of this first induction phase and the results determine treatment:

• Standard risk: MRD ≤0.05% at the end of Induction #1
• High risk: MRD >0.05% at the end of Induction #1

Up to five more treatment phases are given to children at standard risk, usually with some combination of the following drugs: cytarabine, L-asparaginase, daunorubicin, thioguanine, and etoposide. Therapy for children younger than four with high-risk disease includes those five drugs plus mitoxantrone.

Treatment was really hard for our whole family. My 1-year-old daughter was inpatient almost continuously for six months. I ran on adrenaline because I had a strong need to stay on top of everything. I needed to take care of my daughter. I needed to take care of my son. I missed time with my husband. And I didn’t take care of myself. After treatment, I really crashed and experienced a lot of PTSD symptoms. I was pregnant with our third child, and I found myself really worried all of the time. It’s been four years and those feelings have finally passed.

Most children with Down syndrome and AML have a very low risk of having disease in their CNS. So if no blasts are found in the CNS at diagnosis, a single dose of intrathecal cytarabine is given during a lumbar puncture.

Two groups of children are considered to have CNS disease:

• Children with cancer cells in the cerebrospinal fluid at diagnosis
• Children with chloromas in the brain at diagnosis

Children with CNS disease are given intrathecal cytarabine (during a lumbar puncture) twice weekly during induction until no cancer cells are found in the CNS fluid, and then two additional intrathecal injections of cytarabine.

Children with other types of AML

The drugs most often used to achieve remission in children with AML (who do not have Down syndrome or the APL subtype) are cytarabine, an anthracycline (e.g., daunorubicin, idarubicin), etoposide, and thioguanine. These drugs greatly depress the bone marrow, giving the child the best chance to enter remission. Side effects, however, can include severe infections and/or internal bleeding. Thus, all children with AML should be treated at a regional children’s hospital that can provide state-of-the-art supportive care during treatment.

My daughter was diagnosed with AML when she was four years old. She was on a clinical trial and was randomized to the experimental arm that used gemtuzumab—a type of targeted therapy. She had five rounds of chemotherapy (cytarabine, daunorubicin, asparaginase, etoposide) and gemtuzumab. She had a week at home between each round. In all she spent 173 days in the hospital. She breezed through the first three rounds, after the fourth round she got a very high fever (105^o) and after the fifth round, she had the high fever again and her heart started to fail (she was diagnosed with a cardiomyopathy). The PICU doctor made us feel better when he told us her clinical evaluation looked much better than the tests suggested. The heart problem has resolved over time, and we don’t think she has any damage from it although she goes for yearly follow-up appointments with the cardiologist.

The following information about standard treatment was accurate in 2017 when this book was being written. However, treatments evolve, so the standard or experimental treatments offered for your child may be different. Standard treatment for AML typically includes three to four cycles of treatment (called phases). The phases for AML are induction and intensification.

The number of times each phase is used depends on risk level (e.g., some children need two induction phases).The first phase (called induction #1) includes treatment with cytarabine, daunomycin, and etoposide. After this phase, several types of tests are done to determine whether children have a low or high risk of relapse. Following are the usual phases of treatment for children and teens with low-risk disease:

• Induction #1: cytarabine, daunomycin, and etoposide
• Induction #2: cytarabine, daunomycin, and etoposide
• Intensification #1: cytarabine and etoposide
• Intensification #2: cytarabine and mitoxantrone

After induction #1, children and teens with high-risk disease usually receive the following treatment:

• Induction #2: cytarabine, daunomycin, and etoposide
• Intensification #1: cytarabine and etoposide
• If a donor is available, an allogeneic stem cell transplant is done (see Chapter 16, Stem Cell Transplantation).
• If no donor is available, intensification #2 is completed using high-dose cytarabine.

Children with chloromas in the eyes or brain at diagnosis are treated the same as other children with AML. In almost all cases, the chloromas disappear during treatment. In cases where the chloromas do not disappear after treatment with chemotherapy, radiation may be needed.

Most children and teens with AML do not have CNS disease at diagnosis. Currently, intrathecal cytarabine is given before each induction phase to prevent disease from developing in the CNS. Children or teens who have disease in their CNS at diagnosis (5 to 15%) receive IT cytarabine twice a week until disease can no longer be found in the cerebrospinal fluid (a minimum of four intrathecal treatments, and a maximum of six treatments, may be given). Children with chloromas in the CNS at diagnosis receive six IT treatments.

My daughter had very high risk AML (WBC 120,000 and FLT3). At the children’s hospital, they offered us the standard treatment (three intense rounds of chemo followed by a stem cell transplant) or a clinical trial, in which the tyrosine inhibitor sorafenib was added to the experimental arm. I was by myself, 500 miles away from home, and had no one else to discuss it with. I signed her up for the trial, and she was assigned to the experimental arm.