Juvenile Myelomonocytic Leukemia (JMML)

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What is juvenile myelomonocytic leukemia (JMML)?

Juvenile myelomonocytic leukemia (JMML) is a rare blood and bone marrow cancer that affects young children.

JMML occurs most often in children younger than age 4. About 10% of cases are in infants younger than 3 months.

Each year 1–2 children out of 1 million are diagnosed with JMML in the United States. That is 25–50 a year.

JMML occurs when bone marrow makes too many white blood cells called monocytes and myelocytes. The cells build up in the liver, spleen, bone marrow, and blood. When this happens, the blood does not work as it should. The body cannot fight infection as well.

JMML can be aggressive. Stem cell transplant is the only treatment that can cure JMML. But in 15% of cases, JMML will go away on its own without treatment. Doctors closely watch these cases.

Risk factors for juvenile myelomonocytic leukemia

Boys are twice as likely as girls to have JMML.

About 90% of children with JMML have changes in certain genes that cause the cancer. These changes are called mutations.

A gene mutation can be passed down from a parent. This is a germline mutation. Or it can occur sometime during the person’s life. This is a somatic mutation.
Knowing the specific mutation and whether it is passed down (germline) or happens later (somatic) is important. These details help decide the treatment.
Children with the inherited disorders neurofibromatosis 1 (NF1) and Noonan syndrome have a higher chance of having JMML.
Having a genetic mutation or condition does not mean you will develop cancer.

Basics of Blood

Learn more about leukemia and lymphoma causes, treatment, and side effects.

Explore the Basics of Blood

Genetic mutations in JMML

The most common mutated genes are:

Gene	Percentage of cases	Features	Treatment
PTPN11 Germline (passed down)	35-40%	- Mild disease - This gene change is linked to Noonan syndrome.	Wait and watch or mild chemotherapy
PTPN11 Somatic (happens later)		- High chance of relapse - Aggressive disease	Stem cell transplant
NF-1 (Germline)	10%	- Children are usually age 5 or older at diagnosis. - Aggressive disease - They may have a higher platelet count and more bone marrow blasts than children with other subtypes of JMML. - Café-au-lait spots on skin (flat, brown patches)	Stem cell transplant
CBL (Germline)	15%	- May have 1 or more café-au-lait spots on skin - In some cases, the disease goes away without treatment.	- Watch and wait in some cases - Stem cell transplant may be an option if the disease progresses.
KRAS (Germline)		- Mild disease	Wait and watch or mild chemotherapy
KRAS (Somatic)	10%	- Occurs mostly in infants - Often linked to monosomy 7 - Aggressive disease - Low risk of relapse after stem cell transplant	Stem cell transplant
NRAS (Germline)	15%	In some cases, the leukemia will go away without treatment. This usually occurs in infants or in cases with G12S mutation.	- Close monitoring in cases that are likely to go away on their own - Stem cell transplant may be an option.
NRAS (Somatic)		There is a high relapse rate after stem cell transplant. This usually occurs in older children with high levels of fetal hemoglobin.	Stem cell transplant

Symptoms of juvenile myelomonocytic leukemia

Symptoms of JMML include:

Fever
Infection
Dry cough
Easy bleeding or bruising
Enlarged spleen or liver
Painless swelling of lymph nodes
Pale skin
Fatigue
Anemia

Diagnosis of juvenile myelomonocytic leukemia

Diagnosis of JMML can be challenging. JMML has symptoms like those of viral or bacterial infections and other childhood leukemias and blood disorders.

Chromosomal and genetic testing is important because the type of mutation can help decide treatment.

Tests to diagnose JMML include:

Physical exam and health history
Blood tests (complete blood count and blood chemistry)
Bone marrow tests
Tests to look at chromosome and gene changes
Genetic testing (skin or hair follicles) to find out if mutations are inherited or acquired after birth

Physical exam and health history
The doctor will check general signs of health. They will:
- Look for signs of disease such as lumps or other things that seem unusual
- Look at the eyes, mouth, skin, and ears
- Feel the patient’s belly for signs of an enlarged spleen, liver, or lymph nodes
- Ask about the child’s personal and family history
- Look for signs of NF1 and Noonan syndrome
They may also do a nervous system exam.
Blood tests
Types of blood tests may include:
- Complete blood count — This test measures red blood cells, white blood cells, platelets, and hemoglobin. Increased monocytes, abnormal forms of myelocytes and monocytes, and low platelet counts may indicate JMML. This test may also show higher levels of fetal hemoglobin, also known as hemoglobin F.
- Blood chemistry studies — This test measures the amounts of certain substances in the blood. An unusual amount of a substance can be a sign of disease. In JMML, patients may have a higher-than-normal amount of gammaglobulin, an infection-fighting protein.
Bone marrow tests

Bone marrow aspiration and biopsy may suggest JMML but do not confirm a diagnosis.

Doctors will order molecular and genetic tests to look for changes in chromosomes or abnormalities in certain genes or proteins. Doctors use these details to make the diagnosis and choose treatment.

Treatment for juvenile myelomonocytic leukemia

Treatment ranges from watchful observation to hematopoietic cell transplantation.

Doctors prescribe treatment based on how well patients are predicted to respond. This approach is called risk-adapted or risk-stratified.

The course of the disease and treatment response varies widely. Doctors may use age, level of fetal hemoglobin, and platelet count in part to help predict these things. Most children require transplant. In about 15% of cases, the disease will eventually resolve on its own without treatment.

Risk-adapted treatment

Low risk

Low risk includes patients with inherited mutation of PTPN11 (Noonan syndrome) or CBL (CBL syndrome). Sometimes these cases go into remission without treatment.

Doctors closely watch these patients. Patients may have chemotherapy if they develop symptoms such as an enlarged spleen and frequent infections.

Intermediate risk

Intermediate risk includes patients with a somatic NRAS mutation who are younger than 1.

Doctors closely watch these patients or treat them with chemotherapy. The drug azacytidine is approved for use in JMML.

Stem cell transplant may also be an option. It is the only treatment for high-risk JMML that offers hope of a cure. Patients must have a suitable donor to get this treatment.

High-risk

High risk may include patients with somatic KRAS, NF1, or PTPN11 mutations. These cases are either predicted to resist treatment (refractory) or likely to come back (relapse).

Doctors may prescribe chemotherapy with the drugs fludarabine and cytarabine.

Stem cell transplant is a possible treatment. Sometimes this procedure is followed by an infusion of natural killer cells, a type of white blood cell. Chemotherapy may be an option. In limited cases, targeted therapy may be an option.

Stem cell transplant should occur as soon as possible after diagnosis. That is because successful transplant rates are highest in younger children. If JMML comes back, a second stem cell transplant and natural killer cell infusion may be successful.

Umbilical cord blood transplants are also a treatment option.

Other treatments may include:

Chemotherapy
Targeted therapy drugs
In rare cases, surgical removal of the spleen if it has become very big

Children with inherited syndromes may have different treatment than children with somatic mutations.

Prognosis of juvenile myelomonocytic leukemia treatment

Stem cell transplant successfully treats more than 50% of cases.

JMML comes back in about 35–40% of children who go into remission with a transplant. Doctors may suggest a second transplant.

Support for patients with juvenile myelomonocytic leukemia

Stem cell transplants can have long-term side effects. These may include problems with growth, puberty, fertility, and organ function. Your care team can offer more details.

It is important to have regular follow-up appointments. Patients should also have good health habits. These include eating healthy foods, doing regular physical activities, and getting enough sleep.

Questions to ask the care team

Is the cause of JMML due to inherited genetic changes or genetic changes that happened later?
What are our treatment options?
What are the possible side effects of each treatment?
What can be done to manage side effects?
Will my child need to be in the hospital for treatment?
Where is the treatment available? Is it close to home or will we have to travel?
Will the treatment affect my child’s ability to have children in the future? What are options to preserve fertility?

Key points about JMML

Juvenile myelomonocytic leukemia (JMML) is a rare form of childhood leukemia that affects young children.
About 90% of children with JMML have changes in certain genes that cause the cancer. Some of these genetic changes are inherited or happen later.
JMML occurs most often in children younger than 4 years. About 10% of cases are in infants younger than 3 months.
Doctors prescribe treatment based on how well patients are predicted to respond. This approach is called risk-adapted or risk-stratified.
Stem cell transplant is the only treatment that can cure JMML. In about 15% of cases, the disease goes away on its own without treatment or less intensive chemotherapy (azacytidine).
Stem cell transplant successfully treats more than 50% of cases. JMML comes back in about 35%–40% of children who go into remission with a transplant. Doctors may suggest a second transplant.

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Reviewed: April 2023