Understanding JMML
Incidence
Signs and Symptoms
Diagnosis
Treatment
Clinical Trials
Outcomes
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Understanding JMML

Juvenile myelomonocytic leukemia (JMML) is an uncommon blood cancer that has features of two other types of blood cancers. For this reason, the World Health Organization (WHO) classified this disease as a "mixed myelodysplastic/ myeloproliferative disease." This relatively new classification (2001) is expected to lead to a better understanding of the disease and to the development of more effective treatments.

JMML begins with one or more changes (mutations) to the DNA of a single cell called a "monocyte." When monocytes leave the blood and enter the tissues, they attack invading organisms and help combat infection and assist other blood cells, such as lymphocytes, in carrying out their immune functions. Monocytes represent about 5 to 10 percent of the cells in normal blood.

JMML cells accumulate in the bone marrow and in other organs, crowding out normal healthy cells and interfering with the normal production of healthy blood cells, such as white blood cells, red blood cells and platelets.

Incidence

JMML accounts for about 1.5 percent of childhood leukemia cases. The disease affects mostly infants and children younger than 6 years. Although it is rarely diagnosed in newborns, many patients are diagnosed at between 3 and 12 months. JMML is more common in males than in females by a ratio of 2.5 to 1.

Signs and Symptoms

Signs and symptoms of JMML may include

• Enlarged liver, enlarged spleen and/or enlarged lymph nodes
• Pallor
• Fever
• Rash

Other symptoms and signs that may occur include developmental delays, decrease in appetite, pallor, irritability and dry cough.

Diagnosis

Before JMML is diagnosed, other potential diagnoses are considered, especially if a child is older than 6 years. For instance, chronic myelomonocytic leukemia, another type of "mixed myelodysplastic/myeloproliferative disease" may occur in young children under 6 years.

The tests used to diagnose JMML include blood tests and bone marrow aspiration and biopsy to check for

• A persistent elevated monocyte count in the blood (greater than 1,000/microliter of blood)
• The absence of the Philadelphia (Ph) chromosome and the BCR-ABL gene rearrangement. The Ph chromosome is an abnormality of chromosome 22 found in the marrow and blood cells of CML patients.
• Less than 20 percent blasts in the blood or marrow

About 50 percent of JMML patients have some red blood cell changes including

• Higher levels of hemoglobin F than is normal for the patient's age
• Low levels of an enzyme called "carbonic anhydrase"
• Expression of the i antigen on the surface of the red cells

About 85 percent of JMML patients have a cytogenetic abnormality. Some of the cytogenetic abnormalities noted in JMML patients include

• Monosomy 7 and other chromosome 7 abnormalities - 25 to 30 percent of patients
• Abnormalities involving chromosomes 3 and 8 - 5 to10 percent of cases
• Mutations of RAS family of genes - 25 percent of patients
• Mutation of the NF1 gene - about 30 percent of JMML patients have the NF1 gene mutation and about 14 percent of JMML patients are also diagnosed with neurofibromatosis 1. Not all children with the NF1 gene mutation develop neurofibromatosis 1. This is a rare genetic condition associated with coffee-colored spots and pea-sized tumors on the skin, freckling in skin areas not exposed to the sun, optic tumors, and developmental abnormalities in the nervous system, muscles and bones.
• Mutation of the PTPN11 gene - 35 percent of patients. Children with JMML who have the PTPN11 gene mutation may have features associated with Noonan syndrome. These typically include heart malformation, short stature, learning disabilities, indentation of the chest, impaired blood clotting and facial changes.

Treatment

Parents are advised to seek treatment from a physician who is experienced in treating JMML or from a physician who is in consultation with a center or physician who has experience treating the disease.

Without treatment, the disease progresses rapidly. There are two widely used JMML treatment protocols:

• The Children's Oncology Group (COG) JMML Study in North America
• The European Working Group of MDS and JMML in Childhood (EWOG-MDS) Study

Neither of these studies has developed an internationally accepted treatment protocol for JMML.

Drug Therapy.  Standard chemotherapy, regardless of the intensity, has proven effective only to a small number of patients. Treatment with 13-cis-retinoic acid (Accutane^®) has shown some responses leading to disease stabilization and partial remission rather than complete remission.

Stem Cell Transplantation.  Allogeneic stem cell transplantation is the only known curative option for JMML patients. This treatment has been noted to achieve long-term survival in up to 50 percent of patients but relapses are known to occur in up to 30 to 40 percent of patients after transplantation. Second transplants have been beneficial for some patients.

For additional information about stem cell transplantation, please see the free LLS booklet Blood and Marrow Stem Cell Transplantation.

Clinical Trials

Patient participation in clinical trials is important in order to develop new and better treatments. Parents are encouraged to talk to their physicians about whether participating in a clinical trials would be a good treatment option for their child. Parents can also call the Information Resource Center (IRC) for more information about clinical trials for JMML.

Therapies currently under study for JMML treatment include

• Etanercept (Enbrel^®) - blocks the hormone "tumor necrosis factor" (TNF), associated with helping the growth of JMML cells.
• Tipifarnib (Zarnestra^®) - may stop the growth of JMML cells by blocking the enzymes needed in the mechanisms of cancer cell growth.
• Second stem cell transplantation - being studied for use in patients who have relapsed after a first transplant.

Outcomes

Parents of JMML patients are advised to discuss survival information with their child's physician. Keep in mind that outcome data can show how other children with JMML responded to treatment, but cannot predict how any one child will respond.

Generally, the outlook for JMML patients is not as good as it is for patients with other childhood blood cancers, such as acute leukemias, chronic myelogenous leukemia and lymphoma. The median survival of JMML patients is less than 2 years. It is important to note that outcome statistics may underestimate survival to a degree since the data may include outcomes for patients who did not receive treatment.

Factors that may indicate a less favorable outcome include

• Age less than 2 years
• Low platelet count
• Elevated hemoglobin F levels.

There have been a few cases of children under the age 1 with Noonan syndrome and a PTPN11 gene mutation where the disease has improved spontaneously.  A few similar cases of spontaneous improvement have been reported in JMML patients with RAS gene mutations.

Get More information

For more information about JMML, read or order online the free LLS fact sheet Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML).

Contact Us

The Leukemia & Lymphoma Society
1311 Mamaroneck Ave.
White Plains, NY 10605

Email us at infocenter@LLS.org or call the Information Resource Center (IRC) at (800) 955-4572.