| Juvenile myelomonocytic leukemia | |
|---|---|
| Classification and external resources | |
| ICD-O: | 9946 |
| OMIM | 607785 |
| MeSH | D054429 |
Juvenile myelomonocytic leukemia (JMML) is a serious chronic leukemia (cancer of the blood) that affects children mostly aged 4 and younger. The average age of patients at diagnosis is 2 years old. The World Health Organization has included JMML in the category of Myelodysplastic and Myeloproliferative disorders.[1] The name JMML now encompasses all diagnoses formerly referred to as Juvenile Chronic Myeloid Leukemia (JCML), Chronic Myelomonocytic Leukemia of Infancy, and Infantile Monosomy 7 Syndrome.
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JMML accounts for 1-2% of childhood leukemias each year; in the United States, an estimated 25-50 new cases are diagnosed each year, which also equates to about 3 cases per million children. There is no known environmental cause for JMML. Since about 10% of patients are diagnosed before 3 months of age, it is thought that JMML is a congenital condition in these infants.
About 80% of JMML patients have some sort of genetic abnormality in their leukemia cells that can be identified with laboratory testing. This includes:
The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood). Most of these conditions are common, nonspecific signs and symptoms.
Children with JMML and Neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):
Children with JMML and Noonan's Syndrome may also exhibit any of the following most-common symptoms associated with Noonan's Syndrome:
The following criteria are required in order to diagnose JMML:[1]
All 3 of the following:
Two or more of the following criteria:
These criteria are identified through blood tests and bone marrow tests.
Blood tests: A complete blood count (CBC) will be performed on a child suspected of having JMML and throughout the treatment and recovery of a child diagnosed with JMML.
The differential diagnosis list includes infectious diseases like Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, histoplasma, mycobacteria, and toxoplasma, which can produce similar symptoms.
There is an internationally accepted treatment protocol for JMML. Currently, 2 clinical treatment protocols most widely used to study JMML and improve treatment for these children are geographically-based:
The following procedures are used in one or both of the current clinical trials listed above:
The theory behind splenectomy is that in JMML, the spleen acts as a trap for leukemic cells, which leads to their enlarged size. The fear is that since radiation therapy and chemotherapy attack active leukemia cells rather than dormant ones, if the spleen is not removed it may harbor JMML cells that can later lead to relapse. The impact of splenectomy for post-transplant relapse, though, is unknown. The COG JMML Study includes splenectomy as a standard treatment for all clinically stable patients. The EWOG-MDS JMML Study allows each child’s physician to determine whether or not a splenectomy should be done, and large spleens are commonly removed prior to bone marrow transplant. When a splenectomy is scheduled, JMML patients are advised to receive vaccines against Streptococcus pneumoneae and Haemophilus influenza at least 2 weeks prior to the procedure. Following splenectomy, penicillin may be administered daily in order to protect the patient against bacterial infections that the spleen would otherwise have protected against; this daily preventative regimen will usually continue until the patient is an adult.
The role of chemotherapy against JMML before bone marrow transplant has not been studied and is still unknown. Chemotherapy by itself has proven unable to bring about long-term survival in JMML.
Radiation to the spleen does not generally result in a decrease in spleen size or reduction of platelet transfusion requirement.
The only treatment that has resulted in cures for JMML is a bone marrow transplant, with about a 50% survival rate. The risk of relapsing after transplant is high, and has been recorded as high as 50%. Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis. A younger age at bone marrow transplant appears to predict a better outcome.
Relapse: After bone marrow transplant, the relapse rate for children with JMML may be as high as 50%. Relapse often occurs within a few months after transplant and the risk of relapse drops considerably at the one-year point after transplant. A significant number of JMML patients do achieve complete remission and long-term cure after a second bone marrow transplant, so this additional therapy should always be considered for children who relapse.
Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:
| Characteristic | Values indicating a more favorable prognosis |
|---|---|
| Sex | Male |
| Age at diagnosis | < 2 years old |
| Other existing conditions | Diagnosis of Noonan syndrome |
Without treatment, the survival [5 years?] of children with JMML is approximately 5%. Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.
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