Pediatric and Adolescent Concerns
What is Pediatric CML?
Pediatric CML is the condition of chronic myeloid leukemia occuring in infants and children. The term "children" is associated with a number of definitions. For our discussions, we refer to the pediatric patient as one between the ages of 0-14 years, and adolescent patients as those 15-19 years of age. A third category of underrepresented cancer patients are those who fall into the young adult category. These are individuals who are 20-39 years of age. Most of the information presented here will refer to pediatric and adolescent patients.
While there are cases of Pediatric CML found across the world, it is in fact an ultra rare disease and accounts for less than three percent of all pediatric leukemias. As a child ages, the incidence of CML increases with children one to fourteen experiencing the disease at a rate of 0.7 cases out of a million children, and teenagers experiencing the disease at a rate of 1.2 cases per million. While the community is grateful that CML in children and teenagers is considered ultra rare, its scarcity creates difficulty for scientists and hematologists who study and treat the disease, as well as families who need community support.
Today, children with CML and their families benefit from the technology that has allowed researchers and clinicians around the world to combine their efforts and join forces to understand more about CML in children. This digital alliance has allowed the exploration and creation of new treatment options, and the expansion of opportunities to find a cure. Look at the material we have included for you here and visit the resources and links provided. If you are interested in seeing a CML specialist, visit our list for contact information.
Treatment Considerations for Pediatric CML
Tyrosine Kinase Inhibitors (TKIs) are the drugs most often used to treat CML today. The drug imatinib(Gleevec®) made by Novartis Pharmaceuticals, is a tyrosine kinase inhibitor and became the drug of choice for adult patients living with CML in the last decade. Imatinib completely changed the way CML was treated.
Prior to the year 2000, both pediatric and adult patients were treated with either traditional chemotherapy, interferon or bone marrow transplants. Most people lived only 3-5 years at that time. Today, both adult and pediatric patients have options that a patient 15 years ago, could not have dreamed possible and an expected life span near that of family and friends without CML.
Treatment of Pediatric CML patients remains largely based on experience with adult subjects in controlled clinical trials for CML. Many of the same monitoring guidelines and treatment guidelines will parallel those for the adult CML patient population. But it is vitally important that one does not treat a pediatric patient as if he or she were simply a small adult. Pediatric CML patients require a careful analysis of factors unique to their age and condition.
There are important differences in the considerations one makes for treating pediatric CML.
(1) Sokol Score - The Sokol score, in use for several decades as a way of assigning adult patients to a stratified risk group, is not as useful in children and adolescents.
(2) Potential Growth Delays - Consideration must be given to growth and development concerns, and the risks of TKIs to a child's physical maturation. A number of case studies include issues of decelerated growth in children on imatinib prior to puberty.
(3) Potential Long Term Effects - There is still much to be learned about the effect of long term use of TKIs on children. Anticipating a much greater lifespan than children with CML just ten years ago, pediatric patients today may be exposed to TKIs for many decades. Adult CML patients also face this unknown and the only way to answer the question of safety in long term treatment with TKIs, is time.
(4) Potential Cardiac Effects - Each of the TKIs has its own side effect profile, but they all have the potential to cause changes in the heart and lungs that may be serious. The collection of thorough baseline studies prior to starting treatment, and careful monitoring after starting treatment, will assist in the identification of young patients who may be at higher risk for problems such as prolonged QT intervals, pleural effusions, etc. There is insufficient data to make assessments which would allow us to predict the development of the more serious potential effects of TKI therapy. At this time there does not appear to be an increased risk in children, beyond that experienced by adults in the larger studies.
(5) Transplant Options - The decision to proceed with transplant is an important one for the patient and the family. There are significant amounts of experience with transplants and children available to consider. Transplants are much safer today than they were in years past, and children in particular, tend to do well compared to their adult counterparts. If your family is considering a Stem Cell Transplant, consider exploring information with Be The Match.
How do pediatric patients take their medicine?
Medication administration in pediatrics is an opportunity for parents and caregivers to practice creativity, patience and self-control. For anyone who has attempted to bribe, manipulate or coerce an unwilling child to take their oral medication, we salute you. Parents tell us that enticing a child to swallow unwanted medication, is almost impossible. We understand that you may be facing this challenge not just one time, but many times, day after day.
While you may be facing a difficult time now, it does get easier, at least for a time. Once you believe you have medication administration conquered, your child grows into an adolescent and new challenges face you each day. But again, it will get easier. Adults experience similar cycles of waxing and waning motivation to take their medications on time, every time. Even well intended adults may wish to hide behind the sofa somedays and take a break from what feels like the daily grind of taking medicine.
It is important for parents and caregivers to understand the VITAL role they play in helping their child achieve and maintain a deep response to their CML medication. Not only do your actions assure that today's dose of TKI is taken on time, but the habits and routines are forming, that will encourage your child to continue proper medication usage for the remainder of his or her life. Parents and caregivers teach children that taking their TKI is something good to do for oneself, and a way of taking care of oneself.
But how can you make a pill or capsule palatable for a young child? With so many limitations on when and how you must take specific medications, taking a TKI on time, every time, can be quite challenging. We have some hints for you that have helped other parents facing similar challenges. The tips are listed below for you to consider.
Imatinib - Use a clear liquid such as water, apple juice or favorite pre-packaged, non-dairy drink to dissolve the imatinib tablet. In the journal BLOOD in February 2012, Dr. Andolina suggests a 2:1 dilution of 2 parts medication (measured in milligrams) to 1 part clear beverage (measured in millileters). If your child was prescribed 400 milligram tablets, dissolve one tablet into 200 millileters of liquid. Most measuring cups will have millileters clearly marked and it is important to actually measure the beverage instead of guessing. Cold beverages seem to work well for most children. If your child has a "sippy cup" or some type of closed-lid cup or glass, you can dissolve the tablet by shaking the container with the lid in place. Avoid milk and other dairy products. Avoid mixed fruit juices which may contain grapefruit or its extract. Check the inside of the glass after your child has taken the medication to assure there are not visible parts of medication clinging to the sides.
Dasatinib - Much less liquid is needed to dissolve Dasatinib. Tablets can be placed in 30 mls of lemonade or apple juice and allowed to sit on your kitchen cabinet for about twenty minutes until the tablet is fully dissolved. Check the inside of the cup for medication residue. If present, add a teaspoon or two of water, lemonade or juice and administer that to your child also to assure that he or she receives the correct full dosage. Fluids can be cold or room temperature but not hot.
Nilotinib - Dealing with the need to take Nilotinib on an empty stomach is one of the most challenging pieces of caring for pediatric CML patients. Remember that this medication does require that it is to be taken on an empty stomach. To best administer the medication, separate the capsule ends with gentle pressure. Spread the medication on a teaspoon, or 5 mls, of applesauce. Have your child take the medicine using small disposable medicine cups or measure one teaspoon of the applesauce and place it into a small disposable water cup. The smallest bathroom cups, purchased with a dispenser and the necessary images of a favorite cartoon character, or riddles or jokes, on the cup. It may seem trivial but these small changes may help you go from arguments at every mealtime, to a more peacable family life around "medicine time."
Treatment Options for Pediatric CML Chronic Phase
Pediatric Chronic Phase CML
Imatinib (Gleevec®) first became licensed for pediatric use in the United States by the Food and Drug Administration (FDA) in 2003. Since that time, it is estimated that there have been just over 200 pediatric participants in controlled clinical trials involving Imatinib®. In controlled clinical trials enrolling pediatric patients in the US and abroad, Imatinib was found to be superior in chronic phase, over other options such as hydroxyruea, cytarabine, interferon or bone marrow transplant.
Today, there are two additional drugs available to pediatric patients.
Dasatinib (Sprycel®) [Bristol Myers Squibb]
Nilotinib (Tasigna®) [Novartis Oncology]
Adult patients who exhibit either resistance or intolerance to initial treatment with TKIs, now have two more options available to them with a third on track for approval in 2013. We list the two currently approved in adults for your reference, although pediatric experience with them is unavailable at this time.
Bosutinib (Bosulif®) [Pfizer] for patients with evidence of resistance or intolerance to other TKI's
Omacetaxine (Synribo®) [TEVA Oncology] for patients with evidence of resistance or intolerance to two or more TKI's
Treatment Options for Pediatric CML Accelerated Phase
Determining the best treatment for a child or adolescent with CML in accelerated phase begins with looking at all possible options. The experiences of children undergoing stem cell transplant are generally better than the experiences of adults. Less aggressive transplant conditioning regimens (the treatments administered to the patient immediately prior to the transplant) may be used in certain cases.
It is important to begin the decision making process by identifying donor options, in case a transplant is determined to be the best course. If you would like information about how you can help families find stem cell donors for their children, visit Be The Match. Adult clinical trials have demonstrated that patients diagnosed in accelerated phase have greater difficulty in achieving and maintaining a deep response to tyrosine kinase inhibitors. For this reason stem cell transplants are often the best course of treatment. Patients considering transplant, are first treated with later generation tyrosine kinase inhibitors, in order to achieve chronic phase status prior to transplant.
Although individual patient situations drive the decisions, the process will likely involve:
- Confirmation of Ph+ CML by bone marrow aspiration and biopsy
- Initiation of treatment with hydroxyurea to reduce the leukemic burden as soon as safely possible. Hydroxyurea will be accompanied by a medication such as allopurinol, which will help the patient eliminate the by-products present when leukemic cells are destroyed. These two medications are typically given for a short time (days to weeks) at the very beginning of therapy.
- Receipt of pathology and laboratory data which will determine the phase of the disease: chronic, accelerated or blast.
- Patient samples will be submitted for possible stem cell transplant matches.
- Initiation of treatment with a tyrosine kinase inhibitor. The condition of the patient, including risk factors or concurrent health problems, will be evaluated and considered when choosing the right tyrosine kinase inhibitor to use. The side effect profiles of each tyrosine kinase inhibitor will also be considered and the best option selected.
- Patient and family will receive information and training in how to safely administer the tyrosine kinase inhibitor. Medication schedules and meal planning will be reviewed to assure that the patient receives his or her medication under the best possible circumstances depending on the drug.
- Patient will return for labwork on a weekly basis in the beginning of treatment. Later, as blood counts normalize, the patient will be returning for labwork less frequently but at least once every three to four weeks.
- Special Note: Monitoring blood counts and evidence of the BCR-ABL transcript, is CRITICAL to the treatment process. It is important to know if a patient is going to respond to treatment as early as possible.
This will allow a medication change to be made sooner, which is paramount in achieving the goals of treatment.This process allows the patient to begin treatment quickly after diagnosis, achieve initial goal of reaching a complete hematologic response, and the time to consider and prepare for transplant.