CAMBRIDGE, Mass.–(BUSINESS WIRE)–Foundation Medicine, Inc. (NASDAQ:FMI) today announced that new data generated with FoundationOne®Heme, its comprehensive genomic profiling (CGP) assay for hematologic malignancies and sarcomas, will be presented at the American Society of Hematology (ASH) Annual Meeting. Data from a broad range of blood cancers, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and non-Hodgkin lymphoma (NHL), including primary central nervous system lymphoma (PCL), demonstrate the value of integrating FoundationOneHeme into clinical care. The data presented is expected to demonstrate the potential for CGP to improve disease classification, to offer personalized prognostic information and to support therapeutic treatment decision making by informing treating physicians about the use of novel treatment options, including cancer immunotherapies.
Objective: Primary myelofibrosis (PMF) is one of the Philadelphia negative myeloproliferative neoplasms (MPN). The main clinical features are obvious physical symptoms and symptomatic splenomegaly. It may be converse to leukemia and has a shortened life expectancy. Nowadays, the therapy for PMF is aimed at maintaining comfort and there is no curative treatment. PMF with myelodysplastic syndrome (MDS), called MDS/MPN-u, is rare and the treatment is complex. In this study, we want to discuss an effective treatment for MDS/MPN via a case report and literature review.
Materials and methods: A female patient was diagnosed with MDS/MPN through bone marrow cytology, immunology, cell genetics, molecular biology, and pathology. She received thalidomide and prednisone as initial treatment. Ten months later, the first-line therapy had failed, she presented with clinically relevant pancytopenia and increased blasts in bone marrow. Because decitabine is one of the first-line treatments for MDS and the patient was frail, she received low-dose decitabine as second-line therapy. Decitabine was administered at 15 mg/m2 once a week for 3 weeks, in a 4 week cycle. If there was improvement the treatment interval was prolonged.
Result: After one cycle, the blasts in bone marrow were decreased to 0.5%. After four cycles, she felt comfortable and hematological improvement was achieved. The treatment interval was prolonged. After eight cycles, the spleen reduced to 2 cm under the rib, and she achieved complete hematological remission. After ten cycles, the mutation of JAK2/V617F expression was decreased from 60.63% to 0.01%. During the therapy, the patient presented with grade III–IV hematological toxicity after the first two cycles, but there were no side effects after subsequent cycles.
Conclusion: Our research showed that low-dose decitabine may be an effective treatment for MDS/MPN, especially in improving physical symptoms and achieving hematological remission. Besides, it may be possible to reverse positive JAK2 mutation.
How to Approach the Conversation with Your Child’s Hematologist
By Nicole Kucine, MD, MS
It can be difficult to know what to expect when your child is being evaluated for an MPN. There is limited guidance on the internet, which can make specialist visits overwhelming to families. As parents, you can expect that you and your child will be asked many questions about symptoms he or she might be having, including headache, abdominal symptoms, rashes, and itching. Your child will undergo a number of blood tests, including some genetic tests, as well as a bone marrow examination. Children who are having symptoms specific to a certain body area may need radiologic tests (such as an ultrasound or MRI.) You should feel free to ask anything you want, and make sure if you are searching the internet you look at reliable sources (such as the MPN Research Foundation, MPN Advocacy Education International, or cancer.gov.) Some of the questions I am often asked include the following:
Does my child have cancer?
This is a tricky question, and others may disagree, but I do not think of children with MPN as having cancer. In adults, the World Health Organization criteria considers MPN to be chronic forms of leukemia. We are still evaluating MPN in children, and at this point it is not clear that they are all the same disorders in kids as they are in adults. I view the classical MPN in children as chronic bone marrow disorders, and while they have the potential to transform to acute leukemia, this is not something that has been reported in the literature. By envisioning these as chronic illnesses, I think it helps to set the expectations for long-term follow-up and aiming for keeping day to day activities as normal for your child as possible.
Does my child need the bone marrow evaluation?
The answer to this is definitely yes. The bone marrow exam is an extremely important part of the diagnostic process. It can provide a lot of information about what is going on with your child’s blood cells at the source. Things like storage iron, fibrosis, and the appearance of the precursor blood cells are studied. The procedure itself is performed with anesthesia to make sure your child is asleep during the bone marrow test and doesn’t remember it. The pain following a bone marrow test is generally very mild, and children may not require any pain medicine or might require a dose of Tylenol.
What type of MPN does my child have?
The diagnostic criteria for the various types of MPN are based on years of study and data on adult patients. They include features like appearance of bone marrow cells, genetic findings, and lab criteria. Making the appropriate classification for adult patients is important for discussions of prognosis and treatment. We do not yet know if we can directly apply these criteria to children, and knowing the exact type of MPN each child has may not be possible. While it is important to gather all of this information in children, it may not be as important to specifically name the exact type of MPN, and “MPN, unclassifiable” is an appropriate diagnosis for a number of children. The decisions about how to counsel families, what treatments may be recommended, and what follow-up is needed, will be made based on a variety of findings.
Does my child require treatment for his or her MPN?
The answer to this question varies, as I do not believe treatment is required for all children with MPN. I usually determine the need for treatment based on an individual child’s symptoms and lab findings. I generally do not recommend treatment for children who are asymptomatic and have reassuring labs. Children with mild symptoms in the setting of a high platelet count can often benefit from low-dose aspirin, as long as they are not showing evidence of bleeding or acquired vonWillebrand disease. Children with high red blood cell counts can also benefit from low-dose aspirin or phlebotomy. When a child has a severe clinical event such as a blood clot, or does not have improvement of symptoms with initial therapy, then cytoreductive therapy is appropriate. Which medication is used should be decided based on a conversation with the family and the treating doctor. I have been asked about what is my “cutoff” for high platelet or red cell counts for treatment, and there isn’t a standard cutoff. For example, I don’t think an asymptomatic child with a platelet count of 1.3 million necessitates treatment if they are feeling well and otherwise healthy. If you asked 10 different hematologists, you would probably get 10 different opinions on when to treat, so I think it’s important to have a conversation with your hematologist about the risks and benefits of different treatments.
While it can be frustrating to be facing a rare disease, there is ongoing research to help us better understand these conditions in children and adolescents. Keeping an open mind and making sure you have good communication with your child’s hematologist is the most important thing you can do.
Dr. Nicole Kucine is an Assistant Professor of Pediatrics in the Division of Pediatric Hematology/Oncology at the New York Presbyterian Hospital/Weill Cornell Medicine. She completed her fellowship training in Pediatric Hematology/Oncology in the combined program of Weill Cornell and Memorial Sloan-Kettering Cancer Center. During this time, she studied MPN and leukemia in the laboratory under the mentorship of Dr. Ross Levine and received clinical training with world-renowned hematologists at Weill Cornell. Seeing children diagnosed with MPN, and the lack of research in the area, she came to realize that there was a great need for experts in the field of pediatric MPN. Dr. Kucine therefore decided to focus her research in this area. She recently completed her Masters Degree in Clinical and Translational Science at Weill Cornell, with her MPN project being her thesis subject. She is dedicated to improving the care of children with MPN, and is working towards this goal by developing the first comprehensive Pediatric MPN center in the nation.
Says Dr. Kucine, “MPN can occur in children and adolescents, and we are making this diagnosis more and more in this age group. Our understanding of these diseases in children is limited, – we have insufficient knowledge of the causes of these conditions, how to classify them, and how best to manage them and counsel families. We need to boost our research efforts in these diseases in order to provide better guidance and therapeutic options for patients and their families.” As part of her research program, Dr. Kucine is developing the first US patient registry specifically for children, adolescents, and young adults with MPN in order to better understand the risk factors, symptoms and complications associated with these diseases, and to survey and track how physicians are treating them. She is developing a transition program to allow young people to seamlessly transfer to an adult hematology provider with specific expertise in these disorders.
In the laboratory, she is investigating the causes and mechanisms of these diseases by developing larger genomic and cytokine studies. Ultimately Dr. Kucine hopes to identify targeted therapies to use in children with MPN. “Working at the Richard T. Silver Myeloproliferative Neoplasm Center at Weill Cornell, along with physicians and researchers at Memorial Sloan-Kettering Cancer Center, I hope to improve our knowledge regarding pediatric MPN and to develop better long-term treatment strategies for these children.”