What is juvenile myelomonocytic leukemia?
Juvenile myelomonocytic leukemia also known as JMML is a malignant blood cell disorder of infancy and early childhood, characterized by enlarged liver and spleen due to abnormal excessive growth of a type of blood cell called myelomonocytic cells.
What are signs of JMML?
Typical signs of JMML include: pallor (appearing pale), fever, infection, skin bleeding, and cough. Most children with JMML have an enlarged spleen and liver, which can lead to a distended abdomen. Many patients also have big lymph nodes. Some children show severe weight loss. Skin rashes are common.
What is the natural course of JMML?
JMML is fatal if left untreated. The median survival time without stem cell transplantation is about one year (meaning half of patients live about this long). Some children with JMML experience a longer course, characterized by temporary clinical improvement in the absence of therapy.
Which diseases can mimic JMML?
Signs and symptoms of an infection can look like JMML. In addition, disorders of blood cellfunction, such as leukocyte adhesion deficiency and some metabolic disorders, can give rise to a clinical and hematologic picture resembling JMML. Therefore, the diagnosis of JMML needs to be carefully established by experienced physicians.
How frequent is JMML?
Epidemiological studies from Denmark and British Columbia show a JMML incidence of 1.2 cases per million children per year. A lower incidence of 0.6 cases per million children per year has recently been reported in the United Kingdom. JMML predominates in infants. Boys are affected more often than girls.
What is the connection between Neurofibromatosis type 1 and JMML?
The association between neurofibromatosis type 1 (NF1) and JMML has long been established. A clinical diagnosis of NF1 is made in approximately 11% of patients with JMML. The risk of developing JMML for patients with NF1 is 200- 350-fold higher than in patients without NF1.
What is the association between JMML and Noonan syndrome?
In rare cases, infants with Noonan Syndrome develop a JMML-like disorder. Noonan syndrome is characterized by distinct facial features, growth retardation, and heart anomalies. Notably, the JMML-like disorder in patients with Noonan syndrome often resolves without aggressive treatment by the time the child turns one year of age.
Is it possible to develo
p the JMML-like disorder with Noonan syndrome after one year of age?
Usually, infants with Noonan syndrome are diagnosed with the JMML-like disorder in early infancy.
What is the role of mutations of RAS and PTPN11 in JMML?
A number of gene mutations are known to be involved in the development of JMML. RAS mutations are observed in approximately 30% of JMML cases while another 35% of patients harbor the PTPN11 mutation. These mutations are not inherited from parents and it remains largely unknown why some children acquire these genetic defects associated with JMML.
Can patients with JMML be cured?
Currently, only hematopoietic stem cell transplantation from another person (sometimes a sibling, oftentimes someone outside of the family) offers the possibility of long-term cure. Donor search should be initiated soon after the diagnosis because data suggest that young age at transplantation is associated with improved survival.
Can patients with relapsed JMML be cured?
Patients who relapsed with JMML have a chance to be cured with a second hematopoietic stem cell transplantation.
If the child with JMML is stable when is the best moment to go to transplant?
After the diagnosis of JMML is established, transplant should be performed after a suitable donor has been identified. Young patients have a better outcome after transplantation than older patients.
Why are cafe au lait spots frequent in children with JMML?
These skin changes are one important sign of neurofibromatosis type 1 (NF1). NF1 is the underlying diagnosis of 10-15% of children with JMML. And conversely, children with NF1 have an elevated risk of JMML. Nevertheless, even in children with NF1, JMML is a rare event.
I hear other parents say that after stem cell transplantation their child is 100% donor. My hospital says that no test can be so precise. Is that true? While it is great if the analysis reveals a result of 100% donor cells, it is also important to realize that these results do not include information on the sensitivity of the test. Ongoing research is focused on designing more precise tests that allow detection residual leukemia cells (e.g. 1 out of 1,000 cells).
If the JMML is cause by a mutation replacing or "correcting" that gene should cure it. How far are we from that kind of intervention?
To date, this kind of gene-therapy is impossible and, to our knowledge, no group is investigating this approach. Gene-therapy has been employed in some genetic disorders, where it is sufficient to correct a small number of cells. In JMML, it would be necessary to correct all leukemia cells, which would be impossible at this time point. Additionally, gene-therapy currently has a risk of inducing leukemia.
Does each child with JMML have a known mutation?
Currently (April 2007) 75% of patients with JMML are identified to have a mutation present in a known gene. The remaining cases are very likely to harbor a mutation in as yet unknown genes.
Why do some doctors advocate the splenectomy and some don’t? I have also heard of partial splenectomy? Which is the right thing to do?
Splenectomy before transplantation may be indicated in patients with very large spleen size in order to accelerate hematologic recovery and reduce the risk of hemorrhagic complications during the transplant. There is no proven benefit of splenectomy for prevention of post-transplant relapse. In most cases, splenectomy is not necessary. The decision has to be carefully made together with the hematologist/oncologist in charge.
Why are children's taste for food altered during BMT?
The high-dose chemotherapy administered before transplant not only affects the JMML cells but other rapidly dividing cells of the body, including those responsible for the taste.
Assuming that both a related and an unrelated match would be available, and considering both the engrafting and the graft versus leukemia effect of GVHD, which one would be best for stem cell transplantation?
Unrelated donor transplant is indicated for all children with JMML who lack a matched family donor. A completely matched related donor is often best but there may be additional factors that need to be discussed with your physicians regarding this choice. To respect a random donor and patient’s privacy, the donor is chosen in an anonymous manner and, thus, the parents have no influence on the final choice of a donor. The final decision is made by transplant experts and is based on many factors that involve donor availability, many different characteristics of the HLA-type (the finger print of a cell), gender, previous viral infections, and blood group.
What are stem cells?
Hematopoietic stem cells are cells in the blood or bone marrow that are capable of producing all mature blood cells including white blood cells, red blood cells, and platelets.
What is entailed in a stem cell transplant?
In hematopoietic stem cell transplantation, strong chemotherapy (with or without radiation therapy) is administered to kill the JMML cells. Unfortunately, normal blood cells are also destroyed by the chemotherapy. Since it is not possible to survive without blood cells, hematopoietic stem cells from a different person (either a relative or unrelated donor) is then reinfused into the patient. These transplanted donor cells amazingly find their “home” in the patient’s bone marrow and produce healthy blood cells.
What are the risks of stem cell transplantation?
There is a low risk that the transplanted donor cells do not grow in the patient. This is called graft failure and a retransplantation is necessary. In addition, during the transplant and after the transplant, there is a high risk of severe infections. Moreover, donor blood cells may attack the patient’s body and cause a disease called graft versus host disease (GVHD). Lastly, relapse of JMML can occur despite transplantation.
How often does stem cell transplantation work?
Currently, transplantation works in approximately half of all JMML patients. However, new protocols are being developed that aim at better outcomes.
If I have a child with JMML, what is the risk to my other children or future children?
There is no evidence that the risk of JMML is increased in siblings. In theory, there is an increased risk in families with familiar neurofibromatosis type 1. Nevertheless, the occurance of JMML in several siblings in a family is exceedingly rare.
What is a monocyte?
JMML cells look like monocytes. Monocytes are white blood cells and part of the human body's immune system that protects against infections. They move quickly (aprox. 8-12 hours) to sites of infection in the tissues. Monocytes have a unique appearance that allows the hematologist to identify these cells.
Are there things we don’t know yet about JMML?
There are many things we don’t know about JMML. Important questions involve the cause of JMML. It is unknown if a single genetic change in a blood cell is sufficient to cause JMML or if several genetic errors are necessary. While at least one genetic change is identified in 75% of all patients with JMML, we do not know which genes are altered in the remaining patients. We need to devolop better therapies including medications that kill JMML cells and cure patients.
Where can I learn more about JMML?
To learn more about JMML talk to your physician. JMML is rare and you may need to inquire at medical centers with expertise in the care of patients with JMML. There is a large volume of medical literature on JMML. However, the language in these articles is mainly aiming at people with a medical background.
What is the requirement for preparing your home before the transplanted child comes home? What needs to be cleaned? What needs to be removed? What risks are there in a home to an immunosuppressed child that need modifications?
After a transplant, the patient’s immune system is weak and cannot fight infections well. Therefore, some precautions should be taken. It is important that you follow your transplant center's and physician’s instructions. Transplant centers may vary in their recommendations. Furthermore, the recommendations may be adjusted to individual circumstances.
The house or apartment should be cleaned thoroughly before the patient returns home from the hospital. Carpets and floors, furniture, drapes should be cleaned. Air conditioning and furnace filters should be changed. Home remodeling should not be undertaken. The patient should not perform cleaning household chores or any yard work.
Handwashing should be done by the patient and caregivers before and after going to the bathroom, touching pets, blowing the nose, or preparing foods. Guests should also wash the hands when visiting the patient.
Most indoor pets may remain in the house, however, reptiles or some birds should be transferred to another household. The patient should not clean the pet’s waste, change the cat’s litter, or clean a bird’s cage. The patient should not sleep with the pet.
No new pets are recommended. Wash hands after direct contact with pets. No direct contact with birds or any farm animal.
Plants may stay in the home. Do not let the patient handle or care for these. Do not let the patient handle the soil. Avoid direct contact with plants, trees, flowers and mulch. No direct contact with fresh cut flowers/Christmas trees is recommended. No yard work, gardening or digging in soil. Wood burning stoves and fireplaces may be used if vented properly. No wood should be stored in the house or handled by the patient.
What is VOD?
Veno-occlusive disease (VOD) is a disease affecting the liver characterized by occlusion of liver blood vessels. VOD is a complication that occurs in up to 25% of patients undergoing bone marrow transplantation. Clinical features of VOD include weight gain, tender enlarged liver, ascites, and increased bilirubin. It often may be associated with renal failure. VOD is felt to be due to injury to the liver venous endothelium from the conditioning regimen. It is also known as sinuosoidal obstruction syndrome.
How is VOD treated?
Treatment for VOD is primarily supportive. Anticoagulation medications have been used with limited success. Defibrotide, an antithromboitic agent, appears to be a promising treatment, which is used in Europe. The drug is not yet FDA approved in the U.S.