What is Juvenile Myelomonocytic Leukemia (JMML) or Childhood Leukemia?
Juvenile myelomonocytic leukemia (JMML) is a rare type of leukemia that is neither chronic nor acute. It starts in myeloid cells but usually doesn’t grow as fast as AML or as slowly as CML. It occurs most often in young children (average age of 2 years).
Symptoms of JMML or Childhood Leukemia
- Pale skin
- Easy bruising
- Trouble breathing (from too many white blood cells in the lungs)
- An enlarged spleen
- Lymph nodes.
Enumerate Risk Factors for Childhood Leukemia?
There are a few known risk factors for childhood leukemia.
- Some genetic factors increase the risk of childhood leukemia
- Some genetic disorders increase a child’s risk of developing leukemia:
- Down syndrome (trisomy 21): develop either acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) than other children, with an overall risk of about 2% to 3%.
- Li-Fraumeni syndrome: change in the TP53 gene
- Fanconi anemia
Certain inherited conditions cause children to be born with immune system problems. These include:
- Wiskott-Aldrich syndrome
- Bloom syndrome
- Shwachman-Diamond syndrome
- Siblings (brothers and sisters) of children with leukemia have a slightly increased chance of developing leukemia, but the overall risk is still low.
- A Woman drinking a lot of alcohol during pregnancy might increase the risk of leukemia in her child
- Influences in our surroundings, such as radiation and certain chemicals, that increase the risk of getting diseases such as leukemias
- Children and adults treated for other cancers with certain chemotherapy drugs have a higher risk of getting second cancer, usually AML, later in life
- The Link between childhood leukemia and household exposure to pesticides, either during pregnancy or early childhood
- Children who are getting intensive treatment to suppress their immune system (mainly children who have had organ transplants) have an increased risk of certain cancers, such as lymphoma and ALL
- Fetal exposure to hormones such as diethylstilbestrol (DES) or birth control pills
- Father’s workplace exposure to chemicals and solvents
- Chemical contamination of groundwater
- Mother’s age when a child is born
- Parent’s smoking history
- Exposure to electromagnetic fields (such as living near power lines)
- Living near a nuclear power plant
- Infections (especially from viruses) early in life
What are the Causes of Childhood Leukemia?
The exact cause of most childhood leukemias is not known. Most children with leukemia do not have any known risk factors. Specific changes in the DNA inside normal bone marrow cells can cause them to grow out of control and become leukemia cells.
A common type of DNA change that can lead to leukemia is known as a chromosome translocation.
What is Philadelphia Chromosome?
A translocation seen in nearly all cases of childhood chronic myeloid leukemia (CML) and in some cases of childhood acute lymphocytic leukemia (ALL) is a :
swap of DNA between chromosomes 9 and 22, which leads to what is known as the Philadelphia chromosome. This creates an oncogene known as BCR-ABL- which helps the leukemia cells grow.
What are the Signs and Symptoms of Childhood Leukemia?
Signs and Symptoms of childhood leukemia:
- Feeling tired (fatigue)
- Feeling weak
- Feeling cold
- Feeling dizzy or lightheaded
- Shortness of breath
- Paler skin
- Easy bruising and bleeding
- Frequent or severe nosebleeds
- Bleeding gums
- Bone or joint pain
- Swelling of the abdomen (belly)
- Loss of appetite and weight loss
- Swollen lymph nodes
- Coughing or trouble breathing
- Swelling of the face and arms
- Headaches, seizures, vomiting
- Rashes or gum problems
- Extreme fatigue and weakness
What All Diagnostic Tests are Required to Diagnose it?
The following regimen shall be followed for diagnosis of childhood leukemia:
- Medical history
- Physical exam
- Complete blood count ( blood test and blood smear)
- Bone marrow aspiration and biopsy
- Lumbar puncture (spinal tap)
- Lymph node biopsy
- Lab tests to diagnose and classify leukemia:
- All samples (blood, bone marrow, lymph node tissue, or CSF) are looked at with a microscope.
- Flow cytometry and immunohistochemistry
- Chromosome tests:
- Fluorescent in situ hybridization (FISH)
- Polymerase chain reaction (PCR)
- Next-generation sequencing (NGS) tests
- Imaging Tests
How is it Treated?
The main treatment for most childhood leukemias is chemotherapy along with a stem cell transplant. Other treatments might also be used in special circumstances.
- Surgery for Childhood Leukemia
- Radiation Therapy for Childhood Leukemia
- Chemotherapy for Childhood Leukemia
- Targeted Therapy Drugs for Childhood Leukemia
- Immunotherapy for Childhood Leukemia
- High-dose Chemotherapy and Stem Cell Transplant for Childhood Leukemia
What is the Role of Immunotherapy in Childhood Leukemia?
Immunotherapy is the use of medicines to help a patient’s own immune system recognize and destroy cancer cells.
- Chimeric antigen receptor (CAR) T-cell therapy: T cells are removed from the child’s blood and genetically altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) that can attach to proteins on leukemia cells and attack them.
e.g. Tisagenlecleucel (Kymriah)
- Monoclonal antibodies: designed to attack a specific target, such as a protein on the surface of leukemia cells Eg.: Blinatumomab (Blincyto), Gemtuzumab ozogamicin (Mylotarg)