Juvenile myelomonocytic leukemia is a malignant form of leukemia that occurs in infants and young children. In many cases, Juvenile Myelomonocytic Leukemia is simply referred to by the abbreviation JMML. In Juvenile Myelomonocytic Leukemia, malignant transformation of hematopoietic stem cells, which are precursors of monocytes, occurs.
What is juvenile myelomonocytic leukemia?
Basically, juvenile myelomonocytic leukemia is considered a hybrid between myelodysplastic syndromes as well as myeloproliferative neoplasms. Juvenile myelomonocytic leukemia is a particularly severe form of chronic leukemia. The disease primarily affects children younger than four years of age. The average age at the onset of the disease is approximately two years. The WHO classifies juvenile myelomonocytic leukemia as a myeloproliferative and myelodysplastic disease. Juvenile myelomonocytic leukemia accounts for approximately one to two percent of all leukemia diagnoses. In the United States, for example, the diagnosis is estimated to occur between 25 and 50 times a year. Thus, one child per million develops juvenile myelomonocytic leukemia each year.
Causes
Numerous different factors are under discussion as potential causes of juvenile myelomonocytic leukemia. However, according to the current state of medical research, the causes of the disease have not been conclusively determined. So far, hardly any environmental factors have been identified that support the formation of juvenile myelomonocytic leukemia. In addition, approximately ten percent of children with the disease are diagnosed before they reach the age of three months. For this reason, it is assumed that heredity plays a special role in the development of the disease. In addition, more than 80 percent of affected patients show a so-called genetic abnormality, which is revealed by laboratory tests in the so-called leukemic cells. Approximately 15 to 20 percent of affected individuals suffer from a mutation in neurofibromatosis type 1. 25 percent of all patients suffer from a mutation in a so-called proto-oncogene, which is responsible for the coding of RAS proteins. Finally, a mutation on PTPN11 is seen in approximately 35 percent of affected patients.
Symptoms, complaints, and signs
In the setting of juvenile myelomonocytic leukemia, numerous symptoms and complaints are possible in affected patients, which vary depending on the individual case, severity, and manifestation of the disease. Some particularly typical symptoms should immediately alarm physicians and parents when they occur in infants and young children. Numerous symptoms in various combinations may indicate the presence of juvenile myelomonocytic leukemia. These include, for example, fever, pale skin, cough, high susceptibility to infection, low weight gain, spontaneously occurring bleeding, maculopapules, or lymphadenopathy. Also, moderate hepatomegaly, leukocytosis, anemia, severe splenomegaly and monocytosis, or thrombocytopenia should prompt appropriate investigations. In some cases, children with juvenile myelomonocytic leukemia and neurofibromatosis 1 also present with specific other symptoms. These include, for example, café-au-lait spots on the skin, multiple neurofibromas, warts in the axillae, an optic glioma, multiple Lisch nodules, and various malformations of the bones. Possible conditions here include a bent leg down the knee, scoliosis, and low bone density.
Diagnosis and course of the disease
As part of the diagnosis of juvenile myelomonocytic leukemia, there are numerous different methods of examination to choose from, and the attending specialist decides on their application after considering the individual case. Basically, three criteria are required to make a definite diagnosis of juvenile myelomonocytic leukemia. These include the absence of the Philadelphia chromosome or the BCR or ABL fusion gene and a proportion of blasts in bone marrow and blood of less than 20 percent. In addition, there are more than ten monocyte units per liter in the peripheral blood. The relevant criteria are analyzed via laboratory tests of bone marrow and blood.The prognosis of juvenile myelomonocytic leukemia depends on how well the affected individual responds to therapeutic measures. Some findings regarding the prognosis of juvenile myelomonocytic leukemia have manifested over time. For example, the survival of young children without therapy is only five percent. Hematopoietic cell transplantation increases the probability of recovery. Here, the survival rate increases to about 50 percent.
Complications
In this disease, leukemia mainly affects young children and infants. Patients usually suffer from pale skin, cough and often a high fever. The susceptibility of patients to infections is also significantly increased, so that infections or inflammations can occur more often. It is also not uncommon for bleeding to occur over the entire body. Furthermore, the affected persons may also show spots, which has a negative influence on the aesthetics of the patient. Likewise, it is not uncommon for various deformities or malformations to appear on the bones of the patients. Reduced bone density can also make it easier for fractures and other injuries to occur. The quality of life of those affected is significantly limited and reduced by this form of leukemia. As a rule, this leukemia can also be treated with the help of stem cells. Further complications do not occur. Unfortunately, the disease cannot be treated on a long-term basis, so that patients may have to rely on lifelong therapy. It cannot be generally predicted whether this will result in a reduction in life expectancy.
When should you see a doctor?
Infants and young children need immediate medical attention as soon as they show symptoms of disease. Because juvenile myelomonocytic leukemia presents with individual and very diverse symptoms, a visit to the doctor is advised when very different abnormalities are seen. Without timely medical attention, the child may die due to the aggressive growth of the cancer. If the child suffers unusually frequently from infections, coughs continuously or has pale skin, a doctor should be consulted. If spontaneous bleeding occurs repeatedly, if the child shows a lack of interest in play activities or apathy, a visit to the doctor is necessary. If there are abnormalities in the skin appearance, the formation of warts or swelling of the upper body, a doctor should be consulted. Protrusion of the abdomen or in the area of the liver are considered worrisome and must be checked. Peculiarities of the skeletal system, malformations of individual bones or deformities are indications of irregularities that must be examined more closely. If there are behavioral abnormalities, changes in personality, or if the child repeatedly expresses states of discomfort, a visit to the doctor is necessary. If there is a decrease in performance, fatigue, an increased need for sleep, or an unusual change in weight, the symptoms should be investigated and a doctor should be consulted. Limitations in vision or hearing are considered further warning signs of existing health inconsistencies.
Treatment and therapy
Various measures are available for the treatment of juvenile myelomonocytic leukemia. However, no treatment protocol with international recognition exists to date. Currently, two primary therapeutic modalities are used for juvenile myelomonocytic leukemia. On the one hand, the affected patients receive chemotherapy or radiotherapy, and on the other hand, stem cell transplantation. In the case of chemotherapy, it appears that it does not provide a long-term cure for the disease. However, there are currently no confirmed research results. Radiotherapy also apparently does not lead to a complete recovery. Thus, stem cell transplantation is the only possibility for a cure. Basically, the younger the patient, the higher the chances of cure.
Outlook and prognosis
The prognosis of juvenile myelomonocytic leukemia is unfavorable in many patients. Even with medical treatment, complications or sequelae may occur. Without medical care, the course of the disease is fatal in well over 90 percent of those affected. According to statistical evaluations, the chances of survival for patients are less than 5 percent.The prospect of a cure improves if a doctor is consulted early, a diagnosis is made and comprehensive medical therapy is initiated. The sooner treatment is started, the better the prognosis. Since the disease occurs in children and infants, relatives have an obligation to have a medical examination initiated at the first irregularities and abnormalities. If hematopoietic cell transplantation is chosen as the form of therapy, the chances of survival increase to approximately 50 percent. This is currently the best treatment option for the disease. Nevertheless, leukemia is still fatal in half of the patients. In addition, it must be examined on an individual basis whether this treatment can be carried out. Transplantation cannot be used for all affected patients. Patients who have achieved recovery may develop Juvenile Myelomonocytic Leukemia again in the further course. The prognosis remains unfavorable if the disease recurs.
Prevention
According to the current state of medical research, there are no known effective measures or methods to prevent the development of juvenile myelomonocytic leukemia in infants and young children. This is primarily because the disease appears to be predominantly genetic in origin.
Follow-up
Follow-up for juvenile myelomonocytic leukemia directly follows treatment. Based on current research, there are currently no preventive measures to protect infants and young children from the disease. However, parents can positively influence the further course of the disease and thus the prospects of cure. Among other things, they should have their children examined regularly so that the doctor can detect the disease as early as possible. If the infants cough excessively, are prone to infections and have a pale skin color, parents should be particularly careful. The quality of life of the little patients and the whole family is drastically reduced, because the treatment is a physical and emotional burden. This is precisely why the assistance of relatives is so important. If hospitalization is necessary, parents can stay with their offspring to relieve their anxiety. If depression develops in the affected parents as a result of the severe stress, they often need their own therapy. Within the framework of psychotherapeutic treatment, they feel valued and find their original strength again. Depending on the course of the disease in the children, they need above all a lot of loving support. Through the emotional care of the family, the infants and toddlers feel cared for, which can have a positive effect on the healing process.
Here’s what you can do yourself
Juvenile myelomonocytic leukemia affects infants and young children, so the responsibility for self-help measures does not lie with the patients themselves. Instead, parents or guardians support the course of the disease and its prospects for cure with their behavior. For example, parents help to ensure that the disease is diagnosed in good time. Early diagnosis has a positive effect on the prospects of cure, so that considerable influence can be exerted here. For example, parents look out for symptoms such as coughing and pallor, fever and increased susceptibility to infection in their newborn children and those of infant age. These symptoms indicate the presence of the disease and prompt parents to have the child examined by a physician immediately. During the treatment of the disease, the quality of life of the patients usually decreases considerably, as the therapeutic measures are physically and psychologically stressful. The children receive emotional support from parents and relatives. Thus, whenever possible, parents stay with the children in the hospital to help them cope with anxiety, especially during longer inpatient stays and medical procedures. If the illness leads to depression or other psychological problems in the patients’ parents, psychotherapeutic treatment must be included.
