We're all about children!
 June 2005
This edition:
Letter from the Chair
The advances made in the hematology/oncology field over the past 25 years have been one of the most rewarding, demonstrating how translation of science and care can combine to create hope and humane treatment. During my career, I have seen patients with leukemia have a virtual death sentence with less than a 10 percent chance of surviving to a cure rate of about 80 percent. This chance for life has been due to the remarkable advances in treatment protocols, which have been methodically followed and revised incrementally. While breakthrough drugs have been important, the meticulous attention to detail in following and testing the outcome of these changes has resulted in remarkable results. In many ways, the various pediatric oncology groups have led the way in translational research. Today, the Darby Children's Research Institute, our oncology group is studying the molecular and biochemical defects that cause leukemia, brain tumors and neuroblastoma - the three most common malignancies in children. This research by Drs. Barreno, Maria and Kraveka will help to create a basic understanding of tumor biology. By establishing a road map of defects that can be used to adjust and target therapies, not just for a specific disease, but also for a specific patient is the future, his new work will allow more precise and efficacious chemotherapeutics. Our hematology and oncology practitioners also manage many patients with non-cancerous blood diseases, such as sickle cell disease, hemophilia, thrombocytopenia, myeodysplasias, and anemia. In the area of sickle cell, we see another attribute of translational medicine, translating knowledge to care. Dr. Sharon Jackson epitomizes this role in her care of patients with sickle cell disease. At MUSC Children's Hospital, we are blessed to have dedicated, skilled practitioners. The future for children with cancer has moved from hopelessness to hope. With these new changes, we are moving from hope to targeted cures that do not leave patients scarred and damaged--from hope to cure. From the translation of knowledge to care, or knowledge to cure, our hematology/oncology team is a beacon of hope for children in South Carolina. Sincerely,  L. Lyndon Key, MD Chair, Department of Pediatrics Feature Story: Division of Pediatric Hematology/Oncology By: Christy Farrell Trio Solutions Inc.
The division treats children with non-malignant and malignant hematological disorders and solid tumors, and is the only pediatric bone marrow transplant program available in South Carolina. As a lead member of the Children's Oncology Group (COG), it participates in the only national cooperative clinical trial group for pediatric cancer in North America. As such, children of South Carolina have access to cutting-edge therapies available only at centers that specialize in childhood cancer. In addition, MUSC Children's Hospital has a nationally-recognized sickle cell program that's one of the largest and most active clinical trials programs in the country. All this taken together, the MUSC pediatric hematology-oncology program has come a long way since 1991, when Julio Barredo, MD was recruited to MUSC. "Our goal when I began was to develop state-of-the art clinical programs in pediatric cancer and sickle cell programs and to establish a comprehensive research laboratory effort in the division," explains Dr. Barredo, MUSC division director of pediatric hematology and oncology and director of the Children's Cancer Program at MUSC's Hollings Cancer Center. "Now our lab serves as a national reference research lab for COG and we developed and conduct two national clinical trials for children with acute leymphoblastic leukemia and large cell non-Hodgkins lymphoma." In addition to the excellent inpatient facilities and services provided by pediatric hematology-oncology unit at MUSC Children's Hospital, an outpatient clinic staffed with trained pediatric oncology nurses provides state-of-the-art treatment and care for children, including chemotherapy infusions and blood product transfusions. Our mission is to treat the child and support our families through the struggles of a cancer diagnosis and treatment. The medical team of childhood cancer specialists also includes social workers, case managers, dieticians, play therapists and psychologists. They are available both for our inpatient and outpatient patients, and our clinical areas include play areas in both locations which are staffed by dedicated child life specialists. Dr. Barredo is quick to note that his division relies on Children's Hospital for pediatric surgical subspecialty and other pediatric subspecialty physicians who are active participants in a true multidisciplinary approach to treating children with cancer and blood disorders. "We're very fortunate that we have a host of surgical specialists who can perform surgical procedures and a radiation oncology department that is adept in treating children of all ages," he says. "No one can do this alone." Our determination to provide the best possible care to our patients has led us to develop comprehensive multidisciplinary clinics and teams in several areas. The division established the Follow-up After Cancer Treatment (FACT), as one of the first groups in the United States that recognized the special medical needs required to follow childhood cancer survivors. This team of experts follows children, adolescents and young adults to monitor for long-term complications resulting from cancer or its treatment, and to determine when proper intervention is necessary. A multidisciplinary pediatric brain-tumor program was developed a decade ago to care for those children afflicted with brain tumors, the second most common type of cancer in children and adolescents. Finally, comprehensive clinics are also offered for patients with sickle cell disease and bleeding disorders such as hemophilia. Research plays an important role in the fight against childhood cancer and blood disorders. Therefore integral to the division's mission is to conduct cutting-edge research with the goal of translating laboratory findings into novel clinical interventions at the patient's bedside. Jacqueline Kraveka, DO is the chair for the national COG trial for large cell lymphoma and a member of the COG neuroblastoma biology group. Her research laboratory studies the biology of neuroblastoma and focuses on increasing our understanding of the mechanisms that lead to these cells becoming malignant and how to exploit these genetic mechanisms in new treatment strategies for this tumor type. Dr. Barredo's area of interest is pediatric leukemia and his long standing efforts have focused on determining how a cancer cell genetic aberrations can determine the way it responds to chemotherapy drugs and novel molecular agents. The ultimate hope is to take advantage of this knowledge by designing new treatments or combination of treatments capable of overcoming resistance and of increasing the cure rate for kids with leukemia. Indeed, some of the previous work conducted in his laboratory has led COG investigators to introduce changes in the way we treat children with T-cell acute lymphoblastic leukemia that resulted in a substantial increase in cure rates. He is also the chair for the COG national trial for the treatment of extramedullary relapse of acute lymphoblastic leukemia. Dr. Bernard Maria, executive director of the Darby Children's Research Institute, also contributes to the research of the division; he studies the biology and treatment of gliomas, the most aggressive type of brain tumor in the central nervous system. The work is focused on mechanisms of tumor cell invasion in the nervous system and how hyaluronan, a matrix molecule, contributes to the invasiveness. Dr. Maria's laboratory has established a long term collaboration with Dr. Bryan Toole, one of the foremost experts on hyaluronan in cancer biology. "Strategies to halt invasion using hyaluronan oligomers are of particular interest given the fact that some surgically inaccessible tumors are resistant to radiotherapy and chemotherapy", said Maria. Dr. Barredo says it's an exciting time for the division. "By being active both in clinical and laboratory research, we have the opportunity and capability to translate discoveries from the lab into new bedside treatment for children with cancer and blood disorders," he explains. Update from the Administrator
When we talk about children we rarely think about major diseases affecting them. We especially do not consider the fact that there are children that get various types of cancer. It just isn't logical to us. Here at the MUSC Children's Hospital we do have many children who come from all over the state and further to seek treatment for oncological issues. The good news is that we have a wonderful outpatient and inpatient program to care for them in a very family oriented manner. Dr. Julio Barredo and his pediatric oncology division work closely with the children, their families and their local physicians to make sure that everyone is involved in the care plans. The staff of the outpatient service and inpatient service also work closely with all involved to make the experience for the child and the family as good as it can be. Using progressive cutting edge techniques, our team has worked with children to have amazing outcomes. We strive to constantly improve our service to our children which is seen in our oncology service. Currently we are striving to make sure that when a child needs to be admitted for chemotherapy we are able to start the process before 7 p.m. This will ensure that the child and family are moved through the process in the outpatient and inpatient area as quickly as possible. Our team understands that this journey of working through cancer is very difficult. The passion they have for working with our children is evident through their actions. Just another example of the fact that MUSC Children's Hospital is all about kids! Children's Research Institute News Brief
The overarching goal of the Developmental Neuro-Oncology Laboratory (DNOL) is to significantly improve survival and quality of life for children with brain tumors. Pontine gliomas represent the fourth most common type of brain tumor in children. The DNOL, directed by Dr. Maria, is found on the 4th floor of the Darby Children's Research Institute within the space assigned to the Childhood Cancer and Blood Disorders Program. Other investigators in the cancer cluster include Dr. Barredo working on leukemia and Dr. Kraveka researching neuroblastoma. Immediate adjoining programs include molecular genetics and pharmacogenetics. The primary translational research themes of DNOL are to model glioma invasiveness in vitro and in vivo, and to explore novel strategies to halt brain tumor dispersal. Current active projects include collaborations with Brian Toole and Suniti Misra (Hyaluronan, see below), Mark Kindy (In Vivo Model), and Dan Knapp, Sunil Patel, Bruce Frankel, Debbie Hazen-Martin, and Cindy Welsh (Proteomics Project). Sandra Tye, who graduated as the top senior at Central Methodist University in Missouri has also joined the lab this month. The initial focus of the new laboratory is on a high molecular weight polysaccharide expressed at elevated levels in the pericellular matrices of gliomas, hyaluronan (HA). HA is particularly important because the extracellular matrix of the brain consists largely of HA complexes. We hypothesize that the interaction of HA with its cell-surface receptor CD44 regulates receptor tyrosine kinase (RTK) activity in glioma cells. Other research has shown that deregulation of RTK activities leads to malignant cellular properties, and some of the RTKs such as ErbB1 and ErbB2 are associated with glioma malignancy. We also hypothesize that extracellular matrix metalloproteinase inducer (EMMPRIN), a cell-surface glycoprotein, stimulates HA synthesis and downstream activities, thus promoting anti-apoptotic pathways, drug resistance, and invasiveness, all of which are important properties of malignant gliomas. Since surgery, radiotherapy, and chemotherapies have been ineffective in treating pontine gliomas, we must develop novel approaches that take advantage of the biology of those tumors. The use of HA antagonists has already proven very useful in identifying which receptors and agents are important in gliomas. One form of an antagonist is a small HA oligomer that competitively replaces the multivalent, signal-transducing interactions of endogenous HA polymer with monovalent, non-signaling interactions. These oligomers have been shown to inhibit phosphorylation and complex assembly of different RTKs. Another type of antagonist is a soluble HA-binding protein that competes for binding with endogenous HA. Thus, by inhibiting RTK activity, the HA antagonists suppress anti-apoptotic pathways and stimulate tumor suppressor expression. As a result, invasiveness, multidrug resistance, and tumor growth in the brain may also be halted. Our goal is to evaluate the use of HA antagonists as a therapeutic modality for invasive gliomas, including pontine glioma. Preliminary results are encouraging because of HA antagonists suppress the activity of specific signaling molecules key to glioma cell dispersal in the brain. Physicians, nurses, and other key personnel at the MUSC Children's Hospital are committed to providing children with brain tumors with the best possible team care available anywhere. Patients and families should also know that there are many people in the Darby Children's Research Institute that they may not meet working hard behind the scenes to move the field of brain tumor research forward. Together, the Children's Hospital and the Darby Children's Research Institute represent valuable resources to the people of South Carolina and the Nation. Mental Health Resource News Brief Mental Health and Developmental Issues in Primary Care Screening for Autistic Spectrum Disorders Autistic Spectrum Disorders (ASD) affect an estimated 4 to 6 out of every 1,000 children and parents typically bring these concerns to primary care health providers. No two children with ASD have exactly the same symptoms and severity of symptoms can vary greatly. The building blocks for reciprocal social and communication skills are delayed or absent in these toddlers. One of the most important developmental differences is a delay or lack of "joint attention" and "reciprocal social interaction". Joint attention is defined as looking back and forth between the same object or event and another person and "connecting" with that person. Reciprocal social interaction involves engaging in many back-and-forth social interactions, such as exchanging lots of emotional expressions, sounds, and other gestures. These delays are found in most children with ASD and rarely seen in children with other types of developmental problems. A child with ASD often: At about 10 to 12 months of age, most typically developing children will immediately look in the direction of the object to which the parent is pointing. They will then look back at the parent and mimic the parent's expression, usually a smile. Children with autism will often ignore the parent. The child may instead take his parent's hand and lead the parent to the object, and sometimes may even place the parent's hand on the object itself. Most children are able to point to objects out of reach that they want by 12 to 14 months. Asking about and observing these simple characteristics can easily be done in the office setting. Specific ASD screening tools, such as the M-CHAT (Modified Checklist for Autism in Toddlers, available at www.firstsigns.org) may be used at the 18 and 24 month well-child appointment to target skills that are typically deficient in ASD. This screen can be completed by the parent in 5-7 minutes, and has a sensitivity of 85-87 percent and specificity of 93-99 percent for ASD. Topics such as this one are discussed at our monthly Promoting Happy and Healthy Youth discussion group in room 377 of Rutledge Tower on the third Tuesday of the month at 8 a.m. Breakfast is provided by Novartis. Mental Health topics pertinent to primary health care are reviewed and any interested health care provider in invited to come bring cases for discussion. Please contact spratte@musc.edu or maciasm@musc.edu for additional information. A special thanks to the following individuals for their efforts in putting together Kids Connection each month. Managing Editor: Bernard L. Maria, MD, MBA Publisher: Jessica Munday (Trio Solutions Inc.) Web design: Jennifer Cherock (Trio Solutions Inc.) and Brian Dadin (Trio Solutions Inc.) Contributing Writers: Lyndon Key, MD; Bernard Maria, MD; John Sanders, Inderjit Singh, PhD, Phillip Saul, MD, Michelle Macias, MD, Eve Spratt, MD and Christy Farrell (Trio Solutions Inc.) |
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