Treatment (childhood acute myeloid leukemia) recommendations depend upon the patient’s state of Acute Myeloid Leukemia. Treatments recommendations depend on the size, grade and type of tumor, metastasis, possible side effects, and patient’s preferences and overall health. The disease state for AML in children is described as untreated AML, complete remission AML, partial remission AML, recurrent AML, and refractory AML. The common treatments for childhood acute myeloid leukemia include chemotherapy (induction chemotherapy and intensification chemotherapy), stem cell transplantation or bone marrow transplantation (autologous (AUTO) and allogeneic (ALLO)), and radiation therapy (external-beam radiation therapy). Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. Refractory AML includes new drugs being tested in clinical trials. Treatment for recurrent AML includes surgery, chemotherapy, radiation therapy, and targeted therapy.
Treatment of Childhood Acute Myeloid Leukemia
These terms help describe the state of disease for AML in children-
The child has not received any treatment except to relieve symptoms of the disease. The blood or bone marrow contains measurable amounts of leukemia cells, and the child may or may not have symptoms and signs.
Complete Remission AML
Post-treatment, there are very few cancerous blast cells in the bone marrow to tell apart from healthy blasts when viewed under the microscope. Traditionally, this signifies fewer than 5% blasts in the bone marrow. New monitoring methods, known as minimal residual disease (MRD; cancer cells not destroyed by treatment) methods, are better able to find low numbers of cancerous blasts and tell the difference between cancerous blasts and healthy blasts. MRD methods helps in determining remission, and recent research showed these methods are better able to predict the chance of curing this disease. The child usually doesn’t have any symptoms or signs of the disease when in complete remission.
Partial Remission AML
The number of cancerous blast cells in the bone marrow decreases after treatment. But can still be visible with the microscope or MRD methods. The child usually does not have any symptoms or signs of the disease, which only matters during initial therapy called induction.
The disease has come back after the child had a period of remission following treatment (complete absence of symptoms).
When leukemia did not go into complete remission after treatment.
“Standard to care” refers to the best-known treatment. In cancer care, different doctors work together to bring out an overall treatment plan for the patient. This is a multidisciplinary team.
Treatments recommendations depend on many factors:
- The size, grade and type of tumour
- Whether the tumour is applying pressure on vital parts of the brain
- If the tumour has increased to other parts of the body
- Possible side effects
- The patient’s preferences and overall health
Chemotherapy uses medicine to kill or stop the growth of cancerous cells. The type of chemotherapy depends upon the stage and overall condition of the patient. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.
A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. It can be one drug at a time or a combination of different drugs simultaneously.
Several treatment regimens involve the intensive use of various drugs. Following these regimens, around 85% of children will have an initial remission, and about 50% to 70% gets cure, meaning that cancer will never return. Children with AML must be under careful observation as during the treatment due to very low blood cell counts the chance of developing infections can increase1.
The drug choice depends on whether the child has previously been treated for AML and other factors. Chemotherapy for AML is normally divided into 2 phases – induction and intensification 2.
uses chemotherapy to destroy as many cancer cells as possible to make the AML go into remission.
destroys any cancer cells that may be hiding after induction chemotherapy has led to remission, which means there are too few to detect by modern tests. Stem cell or bone marrow transplantation also can be used for intensification therapy.
The side effects of chemotherapy depend on the patient and the dose used. Still, they can include fatigue, low blood cell counts, risk of infection, hair loss, nausea and vomiting, loss of appetite, or diarrhoea.
These side effects usually disappear after treatment. The severity of side effects can also be due to other factors, including genetic differences, drugs and the child’s overall health and well-being.
Most children might have similar initial treatments. However, doses or schedules may vary based on the side effects. This is a constant balance between destroying all the cancer cells and avoiding severe side effects. The child’s doctor will discuss changes to the treatment plan with you as needed, and not all children will require their chemotherapy changed.
Subtypes of Childhood AML
There are two very unique subtypes of childhood AML that requires different treatment from the other subtypes –
Children with Down syndrome who develop AML under four years of age
The AML that grows, in this case, is more sensitive to chemotherapy, and less intense chemotherapy may be used with excellent cure rates of nearly 90% survival at five years 3.
Acute Promyelocytic Leukemia (APL) with PML-RARA
This leukemia results from 2 genes, PML and RARA, which are brought next to each other due to chromosome abnormalities. There are two drugs called all-trans retinoic acid (ATRA) and arsenic trioxide, unique agents, unlike traditional chemotherapy. This treatment approach has achieved excellent response rates above 90% when combined with chemotherapy 4. Other studies have shown a similar benefit when both drugs are used without chemotherapy.
The medications for cancer are still under research. Talking to the child’s doctor is usually the best way to know about the medications prescribed, their purpose, and potential side effects or interactions with other medications. It is also essential to let your doctor know if the child is taking other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs may interact with cancer medications.
Bone Marrow transplantation/stem cell transplantation
Children with AML have different recurrence risks depending on the AML’s subtype. Recurrence is when the leukemia returns following treatment. For children having a higher risk of recurrence, it is more likely that the doctor will suggest stem cell/bone marrow transplantation to help prevent a recurrence.
A stem cell transplant is a medical process in which bone marrow that contains the cancer is replaced by highly specialized cells. These cells, known as hematopoietic stem cells, develop into the healthy bone marrow. Hematopoietic stem cells are the blood-forming cells found in the bloodstream and the bone marrow. These stem cells form all of the healthy cells in the blood. Presently, this procedure is more commonly called a stem cell transplant than a bone marrow transplant. It is because the stem cells in the blood typically being transplanted, not the actual bone marrow tissue.
Stem cell transplantation aims to destroy all cancer cells in the blood, marrow, and other body parts using high doses of chemotherapy or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow 5. The doctors use chemotherapy or radiation therapy to destroy the cancer cells before the transplant.
There are two types of stem cell transplantation depending on the source of the replacement blood stem cells:
ALLO transplantation is the most common type for AML. An ALLO transplantation uses donated stem cells from a related or unrelated donor.
AUTO transplantation uses the patient’s stem cells.
For children having a higher risk for AML recurrence, when a related donor is available, ALLO stem cell transplantation is the more preferred treatment option after a child has a first remission. Thus, for children having the highest risk of recurrence and the lowest chance of recovery, stem cell transplantation with a related or unrelated donor is often useful after the child has a first remission.
In the past, transplantations were not done from unrelated donors unless the AML had recurred. However, the safety of using stem cells or bone marrow from unrelated donors has improved, and these types of transplants are being used more to prevent recurrence for children having high-risk AML. Clinical trials are researching the use of unrelated donor transplants for patients with AML with certain high-risk features. Examples include a chromosome abnormality called monosomy seven or a child who doesn’t experience remission after their first induction chemotherapy.
Side effects depend on the type of transplant, the child’s general health, and other factors.
Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. The most common radiation treatment type is external-beam radiation therapy, in which doctors give high radiation from the machine outside the body. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period.
Radiation therapy for AML is good option only if cancer has spread to the brain and doesn’t respond to systemic chemotherapy given into a vein or chemotherapy delivered into the spinal fluid. T therapy may also treat a chloroma when chemotherapy has not fully worked. Radiation therapy may also help during a stem cell or bone marrow transplant. Radiation therapy prepares the body to receive a transplant.
Side effects from radiation therapy can include mild skin reactions, upset stomach, fatigue, and loose bowel movements. Most side effects go soon after treatment. However, radiation therapy can sometimes interfere with the average growth and development of the child’s body and brain. Therefore, whenever possible, doctors use chemotherapy as the first option to avoid radiation therapy.
Cancer and its treatment have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care. Palliative care also includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies.
Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.
Remission and chance of recurrence
Remission is when there is no more detectable cancer cells and symptoms. This may be called having ‘no evidence of disease’. A remission can be temporary or permanent. Therefore, many people worry about the recurrence of cancer. The doctor performs another round of tests to know the extent of the recurrence. Mainly the treatment plan includes the treatments explained above, like surgery, chemotherapy, radiation therapy, and targeted therapy.
Care and Concern
It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. And so they will ensure that a person is physically comfortable, free from pain, and emotionally supported.
- 1.Kim H. Treatments for children and adolescents with AML. Blood Res. Published online July 31, 2020:S5-S13. doi:10.5045/br.2020.s002
- 2.Molgaard-Hansen L, Glosli H, Jahnukainen K, et al. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study. Pediatr Blood Cancer. Published online December 22, 2010:1222-1229. doi:10.1002/pbc.22931
- 3.Caldwell JT, Ge Y, Taub JW. Prognosis and management of acute myeloid leukemia in patients with Down syndrome. Expert Review of Hematology. Published online September 18, 2014:831-840. doi:10.1586/17474086.2014.959923
- 4.Gurnari C, Voso MT, Girardi K, Mastronuzzi A, Strocchio L. Acute Promyelocytic Leukemia in Children: A Model of Precision Medicine and Chemotherapy-Free Therapy. IJMS. Published online January 11, 2021:642. doi:10.3390/ijms22020642
- 5.Selim A, Alvaro F, Cole CH, et al. Hematopoietic stem cell transplantation for children with acute myeloid leukemia in second remission: A report from the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group. Pediatr Blood Cancer. Published online May 20, 2019. doi:10.1002/pbc.27812