1.Hematology/Oncology Fellowship Overview The University of Wisconsin provides a unique environment for the training of physicians in pediatric hematology/oncology. Our program is designed to train primary careeducated pediatricians to become academic leaders in the care of hematologic/oncologic disorders in children, adolescents, and young adults. Fellowship training will provide the clinical and research experience necessary to treat a wide variety of related problems and will allow the physician to become a teacher, clinician, and researcher as well as to receive board certification in pediatric hematology/oncology. The primary purpose of our program is to prepare trainees for a career in academic pediatrics and to develop their clinical competence in the field of pediatric hematology/oncology. We provide diverse basic scientific training opportunities with an extensive program of clinical investigation. The program has the following goals: General goals: Development of strong, effective interpersonal skills to lead a multidisciplinary care team and interact effectively with patients who are either chronically or acutely ill. These patients come from diverse backgrounds and have different needs. Development of critical skills in the analysis of scientific literature Development of teaching skills Dedication to lifelong self-education Clinical competence in pediatric hematology/oncology: Development of a knowledge base in the pathophysiology of hematologic, immunologic, and oncologic disorders; the pharmacology and use of chemotherapeutic agents; the fundamental principles of radiation oncology; blood banking; coagulation; nutrition and bone marrow transplantation; and the diagnosis and management of infectious complications seen in the immunosuppressed host Development of a systematic, logical approach to clinical decision making. Expert use of the broad databases of history, physical examination, and laboratory evaluation to establish a diagnosis. Inclusion of ethical, socio-economic, and physiological considerations to develop a comprehensive treatment plan appropriate to the unique circumstances of each patient. Development of competence in design and conduct of a research project (clinical or basic): Identification of research/study questions Formulation of testable hypotheses Experimental design, along with identification and use of appropriate controls Analysis of obtained results and application of statistical principles Preparation of a manuscript that reports research results

2. Clinical Experience The University of Wisconsin Hospital and clinics provide primary multidisciplinary care for approximately two million people in Wisconsin and northwestern Illinois. The division of pediatric hematology/oncology treats approximately 100 new oncology patients and 150 new hematology patients each year. On average, ten children undergo bone marrow transplantation each year. The division participates in pediatric phase I, II, and III trials of cytotoxic and biologic anticancer therapies. The division is responsible for the care of infants, children, and adolescents with primary hematologic or oncologic disorders, and participates in the care of infants, children, and adolescents with hematologic complications of other disorders. The division shares responsibility for the training of medical students, residents, and fellows. Fellows will receive broad clinical experience in the practice of pediatric hematology/oncology in concert with guidelines from the American Board of Pediatrics and Sub-board of Pediatric Hematology/Oncology. Objectives 1. To gain broad clinical experience in the diagnosis and management of pediatric hematology/oncology, including, but not limited to, malignancy of infants, children, adolescents, and young adults, nonmalignant hematology, including bone marrow failure syndromes, autoimmune diseases of the blood, coagulopathies, thrombophilias, hemoglobinopathies, thalassemia syndromes, BMT, and peripheral stem cell transplant 2. To achieve competence in marrow ablative therapy and stem cell rescue, as well as in the safe administration of non-ablative chemotherapy to children with cancer. 3. To achieve competence in the interpretation of peripheral blood smears, bone marrow aspirates, bone marrow biopsies, CSF cytospins, tests of blood clotting and fibrinolysis, platelet function, neutrophil function, hemoglobin electrophoresis, osmotic fragility, RBC enzyme assays, immune function, DNA repair, tissue typing, and blood typing 4. To achieve competence in the performance of bone marrow aspirates and biopsies and lumbar punctures with intrathecal administration of chemotherapy 5. To demonstrate initiative and skill in self-teaching and the use of information to devise sound management strategies for patients with novel or unique problems 6. To demonstrate understanding of the methodologies of clinical research for thoughtful evaluation of results published or presented 3. Summary of Clinical Rotations Inpatient Rotations Goals and Objectives: 1. To develop a broad fund of knowledge regarding the pathophysiology of all childhood malignancies, bone marrow failure syndromes, coagulopathies, thrombophilias, hemoglobinopathies, and thalassemia syndromes 2. To understand and execute the most efficient and cost-effective evaluation processes for the diseases mentioned above 3. To design a treatment plan for all diseases mentioned above 4. To conduct consent for treatment conference with the family 5. To implement changes of therapy, goals, and end-of-life care conferences with families 6. To write chemotherapy orders according to hospital policy 7. To perform lumbar punctures, bone marrow aspirates, and bone marrow biopsies on primary patients and keep a log of such procedures 8. To direct inpatient rounds with residents and students 9. To provide didactic teaching sessions to pediatric residents on inpatient service 10. To be the primary on-call physician at night and on the weekends with attending backup 11. To understand acute and chronic side effects associated with chemotherapy 12. To understand indications for and risks of transfusion therapy 13. To assist in bone-marrow harvesting The first year is largely devoted to clinical training and the development of expertise in procedures, diagnosis, and treatment plans. In addition, fellows gain expertise in terminal care of oncologic patients. Approximately half the year is spent on the inpatient service. Fellows oversee the delivery of pediatric care and take progressively increased responsibility for the diagnosis and management of subspecialty patients. They participate in the supervision and education of the general pediatric house staff, in collaboration with the faculty physician, and gain increased independence as warranted by demonstrated perception, knowledge, judgment, and communication skill. Fellows perform all procedures until they are completely competent, after which time, they teach pediatric residents how to 4. perform the procedures. They write all chemotherapy orders and have them checked by the attending and the pharmacy. The inpatient attending takes primary responsibility for all new inpatients. Whenever the fellow is on the inpatient service, these patients are assigned the fellow as their primary with the faculty attending as the supervisory physician. The inpatient service is composed of the attending, fellow, PGY-2, and two PGY-1. The PGY-1 follows the patients assigned to him or her, writes routine orders (except for chemotherapy), and provides general pediatric care. Fellows and PGY- 2 supervise PGY-1 along with the attending on service. The fellow is responsible for subspecialty diagnosis, performance of procedures, writing chemotherapy orders, and supervising chemotherapy administration. The fellow is continuously supervised, but he or she is expected to assume an increasing role in patient care and teaching of the house staff. Summary of duties of the inpatient fellow: Perform all histories and physicals on new patients and inpatient consults Perform all procedures on patients (lumbar puncture with intrathecal chemotherapy, bone marrow aspirate and biopsy, and bone marrow harvest) Read all peripheral blood smears, bone marrow morphology, CSF cytology, and surgical pathology with pathology faculty Review all imaging studies with radiology faculty Supervise general pediatric workups and management and discharge plans of pediatric residents Write all chemotherapy orders and review with inpatient attending and pharmacy Conduct family conferences regarding diagnosis, management plans, prognosis, and participation in research studies Participate in the teaching sessions for pediatric house staff The fellow is expected to gradually increase his or her role in all these duties and ultimately to act as a team leader. During the third year, fellows spend four to eight weeks pre-tending. They are expected to function as junior faculty, round with pediatric residents without attending, and organize the didactic sessions for the team. After rounds with the team, fellows round alone with the attending on service and help prepare documentation for the attending. This stage serves as the final preparation period to ensure the fellows readiness to assume faculty status the following year. 5. Outpatient Rotations Goals and Objectives: 1. To attend every clinic held by Pediatric Hematology/Oncology faculty 2. To evaluate outpatients who are seen on an urgent basis or for scheduled chemotherapy 3. To communicate promptly and effectively with referring physicians and consultants by phone and dictation of correspondence 4. To perform diagnostic and therapeutic procedures on patients seen 5. To understand policies and procedures regarding chemotherapy and blood- product administration 6. To attend outreach clinics (as schedules allow) dedicated to hematology consults and off-therapy surveillance visits for oncology patients 7. To be the primary on-call physician one weekend per month. During outpatient rotations, fellows attend eight half-day clinics under the direct supervision of faculty physicians. The fellows time is divided between hematology and oncology clinics, which meet simultaneously. Outpatient fellows are responsible for answering telephone calls from patients, seeing drop-in patients, and working with nurses to coordinate clinics. The outpatient fellow also attends monthly neuro-oncology clinic and long-term follow-up clinic of oncology patients who have completed their therapies. During outpatient rotation, the fellow attends weekly half-day hematology/hemophilia clinic, which includes patients with hemoglobinopathies, disorders of coagulation/hemostasis, white blood cell disorders, etc. This clinic is supervised by Dr. Carol Diamond. 6. Palliative and End-of-Life Care Rotation (Supervised by Dr. Margo Hoover-Regan) We recognize that most of our fellows have had very little exposure to this important part of medicine in their previous training. Palliative and end-of-life care comprise an integral part of pediatric hematology/oncology clinical work. For these reasons, fellows are required to do a palliative and end-of-life care rotation during the first (clinical) year of fellowship. Dr. Margo Hoover-Regan supervises this rotation. Palliative Care and End-of-Life Care Curriculum (Curriculum organized and conducted by Dr. Margo Hoover-Regan) Objectives: 1. To understand the basic philosophy of palliative care as it applies to children who live with life-threatening illnesses 2. To learn to effectively manage pain and other symptoms common to children with cancer (nausea, vomiting, fatigue, etc.) 3. To learn principles of effective communication with cancer patients and their families, especially in regard to difficult conversations about prognosis, transitions in goals of therapy, limitation or withdrawal of life-sustaining therapy, etc. 4. To be aware of some of the key ethical issues in pediatric palliative care 5. To learn to care for a child dying of cancer or complications of cancer treatment Objectives will be achieved by attending rounds with the palliative care team an average of once a week for four weeks and by attending didactic sessions. The fellow will attend rounds, which will last two to four hours each. This will involve attending scheduled, multidisciplinary UWHC Palliative Care service rounds as well as bedside rounds to current inpatients about whom the Palliative Care team has been consulted. Typically, one to six patients are seen or discussed in either of these scenarios. Once during the rotation, the fellow will also make rounds with a hospice physician at HospiceCare in Madison (to be confirmed with HospiceCare). Didactic sessions with Dr. Hoover-Regan will cover the following topics: 1. Management of pain and other symptoms 2. Advance care planning 3. Optimal communication with patients and families, including delivery of bad news and collaborative decision making (attention will be given to cultural sensitivity) 4. Ethical issues in palliative care 5. Care of pediatric oncology patients at the end of life 7. Format for these topics may be one-on-one teaching sessions, case presentations and discussion, lectures presented for Palliative Care rounds, pediatric hematology/oncology educational conferences, etc. 8. Introduction to Biomedical Research (Supervised by Dr. Sinisa Dovat) One of the most difficult decisions that a fellow has to make during the fellowship is how to choose a research project and mentor. Most of our fellows have had limited exposure to research in the past. The purpose of this rotation is to help fellows decide what kind of research they are interested in, who would be the best mentor for a particular project, and how much time they would like to dedicate to research. We would like to emphasize that the research component of the fellowship is individually tailored. Some of our fellows are very clinically oriented, some want to become physician-scientists with more bench-type basic research, and others prefer translational research. We respect each fellows choice, and we try to provide the best guidance to achieve research goals. For example, if a fellows major interest is in palliative and end- of-life care, we would provide extensive clinical experience in this field during the second and third years of fellowship, but we would also offer several projects (clinical, translational, or basic science) that are relevant to this topic to provide the fellow with an extra edge for the future academic career. We want to stress that research projects are not designed to interfere with the clinical experience of our trainees but rather to provide a different perspective to the clinical problem and to enhance the academic potential of our fellows. We are very committed to the education of our fellows, and we believe that the strength of our program is best measured by the degree of success in the academic careers of our former fellows. Introduction to Biomedical Research Curriculum (Curriculum organized and conducted by Sinisa Dovat, M.D., D.Sc.) Objectives: 1. To understand the basic philosophy of research and its significance in advancing clinical care of pediatric hematology/oncology patients 2. To learn the difference between basic, translational, and clinical research. 3. To learn the principles of grant application, scientific presentation of data at meetings, and scientific paper writing 4. To be aware of some of the key ethical issues in research 5. To develop critical thinking with regard to presented and published scientific results 6. To establish individual priority with regard to involvement in research during fellowship Objectives will be achieved by attending lab meetings at the labs of Dr. Sondel and Dr. Dovat once a week (two to three hours each) for four weeks, attending the Immunology Journal Club once a week for four weeks (Tuesday mornings), attending Science in Medicine Seminars, and attending didactic sessions. The fellow will learn how data is presented and participate in discussions. Typically, 9. one to two projects are discussed in each of these meetings. The fellow will also be assigned to read relevant scientific publications. Didactic sessions with Dr. Dovat will cover the following topics: 1. Basic, translational, and clinical research 2. Ethical issues in research 3. Grant application 4. Research in academic medicine 5. Presentation of research results (through publications and at scientific meetings) The format for these topics may be one-on-one teaching sessions. As part of this rotation, fellows will also complete a Short Course in Clinical Research. 10. Radiation Oncology (Supervised by Dr. Kristin Bradley) The following are learning objectives for a pediatric hematology/oncology fellow during rotation through the radiation oncology department: 1. Gain a better understanding of the role that radiotherapy plays in pediatric malignancies, including: Identify childhood cancers in which radiation is commonly used in the treatment strategy Understand why radiation therapy is employed for some cancers and not for others Appreciate the difference between local control and systemic disease and the role that radiotherapy plays 2. Become familiar with the process of radiation therapy planning and delivery: Understand the difference between traditional 2-D based treatment planning, conformal 3-D treatment, and intensity-modulated radiation therapy (IMRT) Observe daily treatments to see the importance of day-to-day setup accuracy and its implication on the occasional requirement for pediatric sedation Evaluate a few treatment plans to see how to target tumors and at the same time try to minimize dose to adjacent normal tissues 3. Learn more about the potential acute and late toxicities of radiation therapy, including: What are the toxicities? What impact do concurrent chemotherapy and radiation therapy have on their incidence and severity? How are the toxicities managed? What do parents and patients need to know about long-term complications? What post-treatment surveillance for and management of toxicities is recommended? 11. Transfusion Medicine/Blood Bank The Transfusion Medicine (TM) rotation is based on the stated needs/goals of the individual fellow. No two rotation experiences are alike. The fellows can choose from the list of possible goals and objectives listed below: 1. Understand the role of therapeutic apheresis in neurologic diseases such as Guillain-Barre and myasthenia gravis and hematologic diseases such as ITP, AML, and thrombasthenia 2. Be able to describe to a patient how apheresis works 3. Discuss the common side effects of apheresis 4. Develop a simple apheresis treatment plan for common conditions for which apheresis is used 5. Describe the etiology and clinical and laboratory presentations of acute and/or delayed transfusion reactions 6. Develop a detailed understanding of platelet refractoriness and its treatment 7. Develop a basic understanding of RBC serology 8. Follow a stem cell collection from apheresis collection through processing and reinfusion 9. Develop a basic understanding of HLA typing 10. Other goals and objectives as desired by individual fellows 12. Hematopathology (Supervised by Dr. Catherine Leith)Peripheral Blood Smears and CBC Results 1. Recognize normal morphology of red cells, white cells, and platelets in blood smears and be able to calculate absolute white cell counts based on differential and WBC 2. Recognize abnormal red cells, white cells, and platelets and common diseases associated with them 3. Know about the normal ranges for blood counts and WBC differential among patients of different ages Red Cell Disorders 1. Be able to classify anemia cases on the basis of bone marrow production (reticulocyte count) and MCV 2. Recognize common types of anemia, including a. Iron deficiency b. Thalassemia + common hemoglobinopathies c. B12/folate deficiency d. Anemia of chronic disease e. Hemolytic anemia f. Aplastic anemia 3. Know basic structure of hemoglobin, expected Hb at different ages, and principle of interpretation of Hb electrophoresis. White Cell Disorders 1. Be able to recognize quantitative/qualitative abnormalities of white cells, including: a. Reactive neutrophilia, eosinophilia b. Reactive lymphocytosis c. Myeloproliferative disorders d. Acute leukemia, including identification of Auer rods Bone Marrow 1. Recognize normal morphology of bone marrow red cells, white cell precursors, and megakaryocytes in bone marrow smears and biopsy sections 2. Recognize abnormal marrow infiltration of the marrow by acute leukemia, lymphoma, and metastatic disease Lymph Node 1. Recognize normal architecture of benign lymph node 2. Recognize lymph node effacement by lymphoma 13. 3. Identify Burkitt lymphoma 4. Identify Classical Hodgkin lymphoma, including Reed-Sternberg cells Specialized Studies in Hematopathology 1. Understand the uses and limitations of flow cytometric testing, immunohistochemistry, cytogenetics, FISH, and molecular studies in formulating a diagnosis and for clinical follow-up 2. Know the classic immunophenotypic markers associated with acute lymphoblastic leukemia (ALL) of T and B-cell types, and acute myeloid leukemia (AML), including CD19, surface light chain, TdT, CD10, CD34, CD3, CD7, CD33, CD117 3. Know characteristic cytogenetic/FISH abnormalities associated with specific ALL subtypes, and their use in risk stratification 4. Know the characteristic cytogenetic/FISH abnormalities associated with Burkitt lymphoma 5. Know the characteristic cytogenetic/FISH abnormalities associated with AML 6. Know the characteristic immunohistochemical staining patterns associated with B-cell and T-cell lymphomas, and Hodgkin Lymphoma 14. Support Nurse Practitioners: The Pediatric Nurse Practitioners (PNP) perform physical exams and recommend therapies. There are four Pediatric Nurse Practitioners who work at the Division of Pediatric Hematology/Oncology. The PNP provides education and counseling to child and family and makes referrals to community agencies. The Inpatient PNP will coordinate the care for children receiving chemotherapy primarily in the hospital. The Outpatient PNP will coordinate the care for children receiving outpatient or Day Treatment therapies. The PNPs will also follow patients being seen for check-ups after therapy. Psycho-Social: Mauricio Infante, MD, is Director of the Child and Adolescent Psychiatry Consultation Service. He and Joel Wish, Ph.D., oversee consultations to the Pediatric Hematology/Oncology service. The child health psychologist provides counseling and support that relate to coping with illness and the impact of illness or injury on the family. The child health psychologist meets with the parents and child while the child is hospitalized and may arrange for additional assistance in coping once the child returns home and returns to school. The Psycho-Oncology team, which includes Dr. Wish, Dr. Stephanie Farrell, Dr. Kathryn Hammes, Ms. Sharon Frierdich, Ms. Kristin Casey, Ms. Andrea Urbon, and Ms. Joyce Kilgore-Carlin, has semi-weekly rounds for families with acute problems and semi-monthly rounds for families with more long-term issues and educational issues. The health psychologist is specially trained to provide teaching and coping strategies for anxiety and stress management and pain management. Child health psychologists facilitate support groups for both children and parents and provide play therapy and family counseling. Social Work: The clinical social worker provides emotional support and counseling for the child and family. They can refer practical and financial resources to help meet individual needs. Along with the health psychologist, the clinical social worker provides support groups and, with the PNP, performs school visits. The fellows will accompany pediatric hematology/oncology social workers, Andrea Urbon, MSSW, and Joyce Kilgore-Carlin, CAPSW, and our health psychologists, Stephanie Farrell, Ph.D., and Kathryn Hammes, Ph.D., when they interview new families with new problems and learn to identify families that need careful observation and further interventions. Nutritionist: A nutritionist is available to provide suggestions to increase or modify the childs nutritional intake based on his or her needs. They are available to offer alternative methods for adequate nutrition and hydration when oral food and liquid intake is decreased. The nutrition and GI service is available for assistance with the provision of parenteral nutrition. Occupational Therapy: The occupational therapist (OT) helps to improve and maintain childrens strength, flexibility, and endurance during their hospital stays. The OT also 15. assists with other areas as needed, such as fine motor skills, coordination, joint movement, and splinting. Daily self-care skills such as feeding and dressing may also be assessed. Follow-up services and home/school programs can be made available after discharge from the hospital. Physical Therapist: The physical therapist (PT) helps children gain or maintain flexibility, strength, endurance, and ability to move. The PT will also obtain and teach children how to use special equipment such as wheelchairs, crutches, or splints if needed. Follow-up services and home/school programs can be arranged at time of discharge from the hospital. 16. On-call Duties Fellows are on call every fourth weekend during the entire three years of fellowship. When on call during the weekend, fellows round on the inpatient service with house staff, students (if any), and the subspecialty faculty. Fellows are not supposed to stay longer than eight hours per day on-site during weekend calls. In case of unusual circumstances (new patient, extremely ill patient, or urgent consult) that require a longer in-house stay, fellows are asked the next day to reduce their in-house duties, so that their in-house duties do not exceed a total of sixteen hours during two weekend days. On-call subspecialty faculty monitor this. Following the rounds, the fellow takes the rest of the call from home, on a beeper. During the first year of fellowship, the fellow does a total of six months on inpatient service. During these six months, fellows spend an average of twelve hours per weekday (total of five weekdays). If circumstances require that the fellow do in-house duties for more than twelve hours in a particular day, his or her duty hours will be reduced the subsequent day in order to maintain an average of twelve hours per day. While on inpatient service, the fellow is also on call during weekdays. The call is on a beeper from home. It is extremely unusual for fellows to have to stay in the hospital overnight. In that unusual circumstance, the fellow is excused from duties the next day. Fellows are instructed to turn off their beepers when they leave the hospital and are not on call. This schedule allows the first-year fellow who is on inpatient service a total of six days away from program duties during the four-week period. The average number of hours spent on in-house duties is sixty-four per week for a four-week period (sixty hours for five weekdays and sixteen hours every fourth weekend). During the first year of fellowship, when a fellow is not on inpatient service, he or she is not on call during the weekdays but continues to be on call every fourth weekend for a total of sixteen hours in-house and the rest made up of on-call duties from home, on a beeper, as described above. During the second and third years of fellowship, fellows have no weekdays on-call service except during the two months of inpatient pre-tending service during the third year. They continue to have on-call duties every fourth weekend as described above. During the entire fellowship, fellows have a total of six days (three weekends) away from program duties during the four-week period regardless of the type of rotation they are doing. 17. Continuity Clinic Fellows have continuity clinics of approximately twenty-five patients. During the first year of training, when the majority of the clinical service occurs, the fellow assumes care for newly diagnosed patients and participates in their diagnostic evaluations, consent conferences, initial therapy, and then, with supervision by attending staff, acts as the primary oncologist or hematologist for the remainder of the patients care -- inpatient and outpatient. The fellow attends clinics when those patients come in for therapy or need urgent or emergent care. Each clinic visit is supervised by attending staff. Since fellowship residents spend six months on inpatient service during the first year of training, we anticipate that fellows will typically follow half of all newly diagnosed patients in their continuity clinics. 18. Research in Pediatric Hematology/Oncology The fellow will have dedicated time during the first year of training to identify the research mentor, define a project, and begin background reading. The second and third years of training are dedicated to learning laboratory techniques and clinical research techniques, which culminate in the publication of working results. Objectives 1. The fellow will design and conduct an appropriate research study. 2. The fellow will achieve competence in statistical analysis of research data. 3. The fellow will present research accomplishments at a national meeting. 4. The fellow will prepare a manuscript for publication. 5. The fellow will complete a course in biostatistics and epidemiology. 6. The fellow will be knowledgeable and sensitive to ethical issues related to clinical and laboratory research. The University of Wisconsin has a vast array of research opportunities in many interdisciplinary and department graduate training programs on campus, all of which are open as potential research training environments for the fellow. Our own division offers a number of strong research programs, and the fellow may wish to choose a division staff member as mentor. Mentors within our division include: *Paul Sondel: basic science training in molecular immunology and gene therapy. Dr. Sondel is the Chief of the Pediatric Hematology/Oncology division. He is a nationally recognized, accomplished physician-scientist for his translational research in molecular immunology and immunotherapy. His work is well funded by two RO1 awards from the National Cancer Institute. Summary of Dr. Sondels research: Professor: Paul Sondel, M.D., Ph.D. Summer 2006 Title: Professor, Departments of Pediatrics, Human Oncology, and Genetics Laboratory: UWCCC, 600 Highland Ave., K4/449 CSC, Madison, WI 53792 Address: UWCCC, 600 Highland Ave., K4/448 CSC, Madison, WI 53792 E-mail address: pmsondel@humonc.wisc.edu Web site: http://www.genetics.wisc.edu/faculty/profile.php?id=144 19. Research Emphasis: Brief Research Summary--Antibody-Directed Cell-Mediated Tumor Destruction: Efficacy and Escape Our team is pursuing mechanisms to induce in vivo activated NK cells to provide anti- tumor benefit. This work uses the strategy of Antibody Dependent Cellular Cytotoxicity (ADCC), whereby tumor reactive monoclonal antibodies can home in vivo to sites of tumor, and facilitate in vivo tumor destruction by IL2 activated NK cells. In murine experimentally induced syngeneic tumor models, we are evaluating the efficacy and mechanisms that enable immune interventions to induce in vivo tumor destruction. This work involves treatment with tumor reactive monoclonal antibodies and their genetically engineered derivatives. Most recently, we have been investigating fusion proteins created by fusing humanized antitumor mAbs to human IL2.We have completed a single- institution Phase I trial of the hu14.18-IL2 molecule in adults with melanoma at the University of Wisconsin Comprehensive Cancer Center (UWCCC), and a Phase I trial in children with neuroblastoma, through the Childrens Oncology Group. Potent in vivo immunological activation has been observed, including clear demonstration that the circulating hu14.18-IL2 molecule has activated NK cells in vivo, and can enable them to mediate tumor-reactive ADCC. Phase II successor protocols have been approved by the NCI. We have shown that the KS-IL2 immunocytokine (IC) induces protective in vivo responses against two separate sub-clones of the CT-26 murine colon tumor transfected to express the human EpCAM molecule. Remarkably, the anti-tumor effect induced by KS-IL2 in BALB/C mice (syngeneic for the CT-26 tumor) is mediated by T cells against one CT-26 sub-clone, and by NK cells against the other sub-clone. These two tumor sub- clones appear to differ only in their levels of MHC-class I expression. In a syngeneic mouse neuroblastoma model, a separate mAb-IL2 IC (hu14.18-IL2) mediates antitumor effects via NK cells. We have recently shown that syngeneic murine neuroblastomas recurring after hu14.18-IL2 treatment have dramatically up-regulated their MHC-class I antigens, to facilitate their escape from NK induced destruction. In this same model, those neuroblastomas that are resistant to T cell mediated anti-tumor effects show a down-regulation of MHC-class-I antigens, to escape T cell recognition. Thus, in both the colon carcinoma and the neuroblastoma models, the level of MHC class-I expression influences whether the IC controls tumor growth in vivo via NK cells or via T cells. Furthermore, these studies show that the preferred mechanism that these tumors use to escape from immunotherapy is the modulation of cell surface histocompatibility antigen (H2K and H2D) molecules, either up or down, depending upon the type of immunoselective pressure they are exposed to. There are ongoing efforts to evaluate the mechanism of tumor escape from immunotherapy in related murine systems and analysis of the mechanisms involved in augmenting antibody dependent cellular cytotoxicity of tumor cells through co- administration of agents that act to augment macrophage (anti-CD40), T cell ( Anti-CD3) or NK cell (IL2/IL-12) mediated killing. 20. Finally, we are investigating the potential antitumor efficacy of macrophages as a separate therapeutic mechanism. In murine studies, both in vitro and in vivo, activation of macrophages through their CD40 surface molecule enables them to be secondarily activated through TLR receptors (4 or 9), to mediate antitumor effects. Studies are under way to determine the mechanism of action for this antitumor effect. Recent Lab Publications (of >320 total): King DM, Albertini MR, Schalch H, Hank JA, Gan J,Surfus J, Mahvi D, Schiller JH, Warner T, KM Kim, Eickhoff J, Kendra K, Reisfeld R, Gillies SD, Sondel PM. A Phase I Clinical Trial of the Immunocytokine EMD 273063 (hu14.18-IL2) in Patients with Melanoma. J. Clinical Oncology 22:4463-4473. 2004. Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Surfus J, Dixon JR, Lode HN, Reisfeld, RA and Gillies SD. Recurrent murine neuroblastomas increase or decrease MHC class I expression to escape NK- or T cell dependent immune destruction. Cancer Immunology and Immunotherapy, 53:41-52, 2004. Buhtoiarov IN, Lum H, Berke G, Paulnock DM, Sondel PM, Rakhmilevich AL. CD40 ligation induces antitumor reactivity of murine macrophages via an IFN gamma- dependent mechanism. J. of Immunology, 174:6013- 6022, 2005. Buhtoiarov IN, Lum HD, Berke G, Sondel PM, Rakhmilevich AL. Synergistic Activation of Macrophages via CD40 and TLR9 results in T cell independent antitumor effects. J. of Immunol.176:309-318, 2006. Lum HD, Buhtoiarov IN, Schmidt BE, Berke G, Paulnock DM, Sondel PM, Rakhmilevich AL. Tumoristatic effects of anti-CD40 mAb-activated macrophages involve nitric oxide and tumor necrosis factor-alpha. Immunology, 118:261-270, 2006. Student availability: One graduate-student spot Funding status: Possibly one additional spot, grant pending 21. *Ken DeSantes: clinical research training in bone marrow transplantation. Dr. DeSantes is Director of the Bone Marrow Transplant Program. His areas of interest include bone marrow transplant for neuroblastoma and non-ablative transplant regimens. Summary of Dr. DeSantes research: I completed my pediatric residency training at Childrens Hospital of Los Angeles and Hematology/Oncology fellowship training at Childrens Hospital and Medical Center in Seattle. After fellowship, I accepted a position at the University of California, San Francisco, in the division of Pediatric Bone Marrow Transplantation. I worked at UCSF for seven years prior to moving to Madison to direct the Pediatric Hematopoietic Stem Cell Transplant program. My research interests include the use of cellular immunotherapy to treat pediatric leukemia and solid tumors and novel therapeutic approaches to treat children with high-risk neuroblastoma. We are currently exploring the use of haploidentical stem cell transplantation, followed by NK cell-selected donor lymphocyte infusions (DLI), to treat recurrent pediatric malignancies. We are evaluating the therapeutic potential of this approach and correlating clinical outcomes with in vitro assessment of NK cell function and subset recovery post-transplant. We are also assessing the effect of killer immunoglobulin-like receptor (KIR) mismatching on in vitro tumor cytotoxicity and transplant outcome. In addition, we are in the process of developing a murine haploidentical transplant model with NK cell-selected DLI in order to discern the effect of various interventions (e.g., cytokine infusions) on tumor growth. We believe this data will provide a rationale for changes in the clinical protocol that will improve efficacy. I am also a member of the Novel Approaches to Neuroblastoma Consortium (NANT), with a specific interest in I-131 MIBG therapy. We are currently developing an I-131 MIBG treatment program at the University of Wisconsin. The new American Family Childrens Hospital will have a state-of-the-art lead-lined facility to accommodate this program. We will be participating in several NANT clinical trials that utilize I-131 MIBG with autologous stem cell support to treat children with very high-risk or recurrent neuroblastoma. The program is expected to be operational by September 2007, and we will be one of five centers in the country capable of administering this therapy. 22. *Sinisa Dovat: basic and translational research in molecular oncology. Dr. Dovat is the Director of Molecular Oncology Research and the Pediatric Hematology/Oncology Fellowship Program Director. His two major research interests include: 1) Regulation of oncogenesis and the cell-cycle progression in leukemia/lymphoma and 2) Pharmacogenomic-based targeted combination chemotherapy for malignant diseases. The National Cancer Institute funds his research. Summary of Dr. Dovats research: Our long-term objective is to understand the mechanisms of gene dysregulation that leads to malignant transformation of hematopoietic cells in humans. The most important difference between cancer cells as compared to normal cells is in their way to divide and multiply. Cancer cells are immortal. They divide fast and they divide indefinitely. Normal cells multiply at a determined rate, and after a certain number of divisions, they die. In cancer cells, the mechanism, which controls the life cycle of the cell, is altered. The life cycle of each cell is controlled by a set of specific genes. The focus of our research is to discover how these genes control cellular fate. In our research, we are focusing on the function of C2H2 zinc finger genes. The C2H2 zinc finger family is larger than any other family of nuclear proteins encoded by the human genome. We are studying the role of these genes in hematopoiesis and the cell cycle. We are focusing our research on identification of biological functions of two zinc finger genes, Ikaros and Helios. Ikaros expression is restricted to hematopoietic cells. Previous data suggest that the deregulation of Ikaros expression leads to the development of leukemia. Our research focuses on signal transduction pathways, which influence Ikaros function. We showed that Ikaros is hyperphosphorylated during mitosis. We found that phosphorylated amino acids are part of the evolutionarily highly conserved sequence. Phosphomimetic studies showed that the cell cycle specific phosphorylation of Ikaros abolishes its DNA-binding in vitro and targeting to pericentromeric heterochromatin in vivo. Phosphorylation was not restricted to Ikaros or to heterochromatin-associated proteins, as a conserved sequence within the ubiquitous transcription factor Sp1was also modified during the G2/M transition. These results suggest that phosphorylation provides a common and perhaps global mechanism for mitotic inactivation of the large C2H2 zinc finger family. We plan to identify kinase(s) responsible for this signaling pathway and to study further how phosphorylation affects the function of C2H2 zinc finger genes and the cell cycle. Helios encodes a protein structurally similar to Ikaros, whose expression is restricted to T cells. Using a transgenic mouse model, we showed that ectopic expression of Helios in B cells leads to development of lymphoma. In the future, oncogenic potential of Helios will be studied. The second project studies myeloid differentiation and genes involved in permanent cell cycle arrest associated with terminal differentiation. We are studying pharmacogenomics of current drugs in order to design a targeted chemotherapy regimen for hematopoietic 23. malignancies. Our goal is to design a combination chemotherapy that would be more efficient and less toxic than the present treatment. Elucidation of the role of Ikaros in the cell cycle in hematopoietic cells and pharmacogenomics of myeloid differentiation will have significant implications for our understanding of the control mechanisms of proliferation of leukemia cells. Although we are currently using leukemia cells as a model, we believe that the results of our discoveries will be applicable to the treatment of other types of cancer. We also expect our results to help explain processes such as immune response, tissue regeneration, and aging. Selected Publications: Ronni T, Payne KJ, Ho S, Bradley MN, Dorsam G, Dovat S. Human ikaros function in activated T cells is regulated by coordinated expression of its largest isoforms. J Biol Chem. 2006; Nov 29 (In Press). Dovat S, Montencino-Rodriguez E, Schuman V, Teitell MA, Dorshkind K, and Smale ST. Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis. J. Immunology 2005; 175:3508-3515. Dovat S, Ronni, T, Russell, D, Ferrini, R, Cobb, BS and Smale, ST: A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains. Genes and Development 2002; 16:2985-2990. Dovat S, Gilbert KA., Petrovic-Dovat L and Rannels DE. Identification of Unique Zinc Finger Genes Expressed in Rat Lungs. Am. J. Physiol. 1998;275:L30-37. Dovat S, Gilbert KA, Petrovic-Dovat L and Rannels DE. Isolation, Cloning and Characterization of RLZF-Y, a Novel Zinc Finger Gene From Rat Lung. Biochim. Biophys. Ac. 1998; 1442:380-388. 24. *Yousif Matloub: clinical research in Acute Lymphoblastic Leukemia (ALL); Dr. Matloub is Clinical Director of the Pediatric Hematology/Oncology division. He is nationally recognized for his expertise in ALL and clinical research training. The National Cancer Institute supports Dr. Matloub as a Childrens Oncology Group (COG) Principal Investigator. *Diane Puccetti: clinical research in Neuro-Oncology; Dr. Puccettis research interests include brain tumors and long-term side effects of chemotherapy. *Carol Diamond: clinical research in disorders of hemostasis. Dr. Diamond supervises the Coagulation Disorder and Hemophilia Center. She also oversees the Sickle Cell Disease Clinic. *Margo Hoover-Regan: Clinical research in palliative care. Dr. Hoover-Regan supervises Palliative Care and End-of-Life Care rotation. She is actively involved in patient advocacy committees. Additional research opportunities relevant to pediatric hematology/oncology may be pursued in the division of hematology of the department of medicine, in the department of radiation oncology, and at the McArdle Cancer Research Center, as well as in any of the other basic science research laboratories on campus. The pediatric oncology program is affiliated with the Childrens Oncology Group as a competitively funded principal institution and with the University of Wisconsin Comprehensive Cancer Center (UWCCC), directed by Dr. George Wilding. Through UWCCC, we participate in joint adult/pediatric efforts in bone marrow transplantation and neuro-oncology. Dr. Paul Sondel directs the Childrens Oncology Group Immunology/Biotherapy Resource Laboratory. The fellow will develop, conduct, and eventually publish at least one research project in the field of pediatric hematology/oncology. Research topics are tailored to the interests of the individual fellow. The entire second year and about 80 percent of the third year are protected time to do research. The fellow is encouraged to take a UW-Madison biostatistics course during the fellowship. 25. Education during Fellowship Although our fellows acquire extensive knowledge of pediatric hematology/oncology during their clinical and research training, we recognize the need for formal courses/lecture sessions in order to enhance the educational experience during fellowship. During training, fellows will participate in the following courses/conference series. Board Review Course (Supervised by Dr. Sinisa Dovat) Our fellows work hard, and the knowledge that they acquire during the fellowship training provides them with a good foundation to successfully pass the Board exam. We have noticed however, that most trainees are anxious about taking the Board exam, so we decided to provide them with an educational tool specifically designed to meet such a need. The Board Review Course is organized with fellows and supervised by Dr. Sinisa Dovat. All fellows are assigned topics, on a rotating basis, from examination outlines on the American Board of Pediatrics (ABP) Web site. The entire scope of the Board examination is covered at least every three years. Presenters are expected to prepare Power Point presentations and handouts. Faculty of the Division of Pediatric Hematology/Oncology supervises every presentation. Handouts and Power Point presentations are archived and are available to all trainees for future reference. We think this approach will ensure that every topic required by the ABP will be covered and that this educational experience will optimally prepare fellows for the Board exam. So far, we have had very good feedback from our current fellows regarding this course. 26. Board Review Course Lecture Schedule for 2006-2007 Date Room Topic 09/12/06 K6/552 Organize+Erythrocyte, Hemoglobin, Fe Metab 09/26/06 K6/552 Fe Def. Anemia and Nutritional Anemia 10/10/06 TBD Hemolytic anemias 10/24/06 K6/552 Hemoglobinopathies 11/07/06 K6/552 Thalassemias 11/21/06 K6/552 Hemostasis, Thrombocytopenia, and Cytosis 12/05/06 K6/552 Coagulation 12/19/06 K6/552 Disorders of Coagulation 01/02/07 NONE HOLIDAYS 01/09/07 K4/418 Hemophilia and vWD 01/23/07 K4/618 Hypercoaguable States 02/06/07 K4/618 Transfusion Medicine 02/20/07 K4/618 Neutropenia/Neutrophilia 03/06/07 K4/618 Monocytes and Lymphocytes 03/20/07 K4/618 Oncology (General) 04/03/07 K4/618 XRT and General Principles of Chemotherapy and Dx Test 04/17/07 K4/618 Chemotherapy I (through Cytoxan) 05/01/07 K4/618 Chemotherapy II 05/15/07 K4/618 ALL 05/29/07 K4/418 AML and CML 06/12/07 K4/418 Hodgkins Disease 06/26/07 K4/418 Non-Hodgkins Lymphoma 07/10/07 K4/418 Osteosarcoma/Ewings sarcoma 07/24/07 K4/418 Retinoblastoma/Hepatoblastoma and HCC 08/07/07 K4/418 Neuroblastic Tumors 08/21/07 K4/418 CNS I (Medullo, Astro, Brainstem and Optic Glioma) 09/04/07 K4/618 CNS II (Pineal, Ependymoma, PNET) 09/18/07 K4/618 Renal Tumors and Gonadal/Germ Tumors 10/02/07 K4/618 Rhabdomyosarcoma and Other Soft Tissue 10/16/07 K4/618 Histiocytic Disorders and Catch-up 10/30/07 K4/618 Prophylaxis and Tx in Immunocompromised Patients 11/13/07 K4/618 Immunodeficiency States 11/27/07 K4/618 HSCT I 12/11/07 K4/618 HSCT II 27. Pediatric Hematology Course (Supervised by Dr. Carol Diamond) Goals By the completion of the fellowship, the trainee should have facility in recognition, diagnostic evaluation, and management of the following disorders. As well, the trainee should have an in-depth understanding of normal hematopoesis and the molecular mechanisms leading to the following disorders: Newborn hematology Neonatal alloimmune thrombocytopenia Autoimmune thrombocytopenia Fetomaternal hemorrhage Alloimmune hemolytic anemia Hemolytic anemias other (e.g., HS) Vitamin K deficiency Anemia of prematurity Inherited coagulapathy Anemias nutritional (iron deficiency and megaloblastic), anemia of inflammation, autoimmune hemolytic anemia, blood loss Qualitative and quantitative disorders of hemoglobin synthesis thalassemias and hemoglobinapathies Red cell diseases enzymopathies, membrane defects White cells alteration in primary or secondary disease, inherited or acquired neutropenia, defects of neutrophil function, lymphopenia and its implications Coagulation normal physiology, fibrinolysis, abnormalities of the factor deficiencies and inhibitors, von Willebrands Disease, hemophilia Hemostasis disorders of platelets, quantitative and qualitative, inherited and acquired, ITP, DIC, TTP, sepsis Thrombophilia inherited and acquired Immunodeficiency states inherited and acquired Bone marrow failure syndromes aplastic anemia, Fanconi, Blackfan-Diamonda Transfusion medicine collection and storage, indications and risks of transfusions, blood banking, iron overload and chelation therapy 28. Pediatric Hematology Course Didactic Sessions During the three-year fellowship, the trainee will attend or prepare a didactic session on the following topics. Every presentation will be critiqued and evaluated by other fellows and faculty. Didactic sessions will be presented as part of an Educational Conference. 1. Newborn hematology 2. Sickle-cell anemia management, current research updates, Journal Club devoted to sickle-cell anemia 3. Thalassemia syndromes diagnosis and management 4. Thrombophilia evaluation, management, and anticoagulation therapy 5. Von Willebrand disease 6. Hemophilia 7. Immune thrombocytopenia purpura 8. Evaluation of hemolytic anemia 9. Bone marrow failure syndromes 10. White blood cells function and dysfunction 11. Transfusion medicine 12. Surgical consideration for the patient with coagulapathy or platelet dysfunction 13. Menorrhagia and the hematologist 29. Pediatric Hematology/Oncology Educational Conference Series (Supervised by Dr. Ken DeSantes) The weekly conference series consists of presentations by faculty members and fellows from University of Wisconsin as well as outside speakers. These presentations are didactic lectures on subjects of clinical relevance. Presentations that are part of the pediatric hematology course curriculum are presented at these conferences. Fellows are required to make three presentations during each year of their three-year fellowship. The Journal Club is organized once a month as a part of the Educational Conference series. Recent papers are recommended by the faculty and selected and presented by fellows. Papers are generally of clinical and translational importance. Responsibility for presentation rotates among all fellows. Didactic Curriculum Covered at Pediatric Hematology/Oncology Educational Conferences Leukemia ALL AML CML Lymphomas Hodgkins disease Non-Hodgkins lymphoma Solid Tumors Brain tumors Neuroblastoma Wilms tumor Soft tissue sarcomas Osteogenic sarcoma Ewings sarcoma/PNET Liver tumors Germ cell tumors Retinoblastoma Bone marrow failure Hemoglobinopathies and thalassemia Disorders of the red cell membrane or metabolism Autoimmune hemolytic anemia 30. Nutritional anemias Inherited and acquired disorders of white blood cells Platelet disorders, including ITP and acquired and inherited function defects Hemophilia, von Willebrands disease, and other inherited and acquired coagulation disorders Hematologic disorders of the newborn Transfusion medicine and use of blood products Congenital and acquired immunodeficiencies Psychosocial Communication Counseling Terminal illness Medical Economics Physiological Support of the Cancer Patient Transfusion therapy Parenteral nutrition Control of nausea Pain management Management of infection in the compromised host Data management Stem cell and bone marrow transplantation and its complications Plasmapheresis Etiology and etiology of childhood cancer Treatment protocols Staging and classification of tumors Surgery Radiotherapy Chemotherapy 31. Basic Science Structure and function of hemoglobin Iron metabolism Phagocytic system and splenic function Cell kinetics Immunology Coagulation Genetics Principles of radiation therapy Characteristics of malignant cells Tissue typing Blood groups Pharmacology of chemotherapeutic agents Microbiology and anti-infective agents in the compromised host Nutrition Molecular biology In addition to the above-mentioned conferences, fellowship residents are encouraged to attend: Human Oncology Grand Rounds (weekly), which consist of presentations by faculty members from University of Wisconsin as well as outside speakers. Fellowship residents are required to do one presentation during the three years of fellowship. There are also numerous lectures available to fellows (seminars of basic science departments, medical school, etc.). These lectures help fellows to become familiar with various research opportunities at the University of Wisconsin. 32. Teaching Experience The goal of the program is to enable trainees to emerge with a variety of teaching experiences, which will prepare them to function as teachers of pediatric hematology/oncology in a medical school faculty position. This competence includes teaching medical students, residents, nurses, and colleagues. Objectives 1. The fellow will participate as a seminar leader in the medical schools hematopathology class for second-year medical students. 2. The fellow will prepare and provide students with formal and informal didactic sessions on general topics relevant to resident training and in concordance with the written competencies of the pediatric hematology/oncology inpatient rotation. 3. The fellow will present at the Multidisciplinary Tumor Board at least four times per year. 4. The fellow will present and then contribute to the curriculum of the Pediatric Hematology/Oncology Division Educational Conference at least three times per year. 5. The fellow will present one Pediatric Grand Rounds and one University of Wisconsin Comprehensive Cancer Center Grand Rounds within the three-year training period. 6. The fellow will become competent in teaching ancillary staff and parents the fundamentals needed for caring for the child with malignancy. 33. Administrative Experience The goal of the program is to introduce the trainees to the administrative responsibilities that they will face as a practicing physician. Objectives 1. The fellow should attend monthly division staff meetings. 2. The fellow should develop a grant proposal under the guidance of his or her research mentor. 3. The fellow should be involved in scheduling, working with home care services, and planning care systems for complex patients. 4. The fellow will participate in the process by which clinical, teaching, and administrative tasks are delegated. Goals and objectives are available in writing and are presented to fellows and faculty every July. The fellowship director meets with the fellows quarterly to discuss the evaluations submitted from faculty and to assess their progress. Program goals and fellows goals are discussed at these meetings. 34. Policies and Procedures of the Pediatric Hematology/Oncology Fellowship Program at University of Wisconsin Madison Department of Pediatrics Pediatric Hematology/Oncology Fellowship Selection Policy Pediatric Hematology/Oncology applicants will be screened according to predefined criteria to ensure that selection is on the basis of applicant preparedness, ability, aptitude, academic credentials, communication skills, and personal qualities such as motivation and integrity. Applicants must meet one of the following criteria to be considered for a Pediatric Hematology/Oncology Fellowship position: 1) Be a graduate of a US or Canadian medical school accredited by the LOME 2) Be a graduate of a US college of osteopathic medicine accredited by the AOA 3) Be a graduate of medical schools outside the US or Canada that are certified by the ECFMG and meet one of the follow criteria: Have US citizenship Have permanent legal residency status in the US (green card) Have or be eligible to have a J-1 clinical visa sponsored by ECFMG Applicants must have satisfactorily completed an ACGMEaccredited pediatric residency or other training considered suitable by the program director. Suitable training may include previous training in surgery or anesthesiology. Candidates who do not fulfill these criteria will be advised by the program director to consult the American Board of Pediatrics regarding eligibility. The department does not discriminate with regard to sex, race, age, religion, color, national origin, disability, or veteran status. Applicants must submit an application form, a curriculum vitae, and three letters of recommendation (one preferably from the residency director). Faculty members in the Division of Pediatric Hematology/Oncology interview all candidates. At the conclusion of applicant interviews, faculty meet as part of an open selection process to discuss and rank the applicants they have met. The Division of Pediatric Hematology/Oncology in the Department of Pediatrics at the University of Wisconsin participates in the NRMP match. Applicants selected will be screened by the Office of Housestaff Administration to ensure that all eligibility requirements have been met. After this has been done, official appointment letters are issued. 35. Pediatric Hematology/Oncology Fellowship Program Policy for Fellow Evaluation, Promotion, and Dismissal Medical knowledge is objectively assessed by in-service SITE examination. The acquisition of other basic competencies (patient care, communication, practice- based learning, professionalism, and system-based practice) is assessed by 360 degree evaluation by faculty, peers, staff, and patients (parents) on a quarterly basis. Residents receive feedback promptly, and evaluations are included in their quarterly evaluations. On a quarterly basis, the fellowship director reviews the evaluations with the PHO resident and provides recommendations and guidance. The Scholarship Oversight Committee (SOC) for each fellowship resident meets every six months. The purpose of the meetings is to evaluate initial plans for the residents scholarly activity (first meeting) and to evaluate progress, suggest direct changes, recommend publication, and suggest new avenues for obtaining grant support (subsequent meetings). The last meeting the SOC provides a final report to approve (or deny) satisfactory completion of the scholarly activity by the fellowship resident. A written report of every SOC meeting is placed in the residents file, and a copy is given to the resident. Criteria for promotion of the resident are based on 360 degree evaluations and continuing progress in acquiring basic competencies and scholarly activity. In order to be promoted, the fellowship resident needs to show consistent improvement in these areas. Division faculty make the decision regarding the promotion, and it is promptly communicated to the fellowship resident. If severe problems arise and the issues are serious or are a result of a pattern, then a meeting is arranged with the resident, the program director, and the division chief. The resident is given an opportunity to respond to the issues. A written evaluation is performed; a copy is placed in the residents file, and the original given to the resident. The evaluation also includes a strategy for correction and a timetable for improved performance. Persistent problems can lead to probation or dismissal. A copy of formal policies and procedures of the Department of Pediatrics is available to all residents. 36. Current In-House Duty Hours for Fellowship Residents (as of 7/2006) Fellowship residents are on call every fourth weekend during the entire three years of the fellowship program. When on call during the weekend, fellowship residents round on the inpatient service with house staff, students (if any), and the subspecialty faculty. Residents are not supposed to stay longer than eight hours per day on-site during weekend calls. In case of unusual circumstances (new patient, extremely ill patient, or urgent consult) that require a longer in-house stay, residents are asked the next day to reduce their in-house duties so that their in-house duties do not exceed a total of sixteen hours during two weekend days. On-call subspecialty faculty monitor this. Following the rounds, the resident takes the rest of the call from home, on a beeper. During the first year of fellowship, the fellowship resident does a total of six months on inpatient service. During these six months, residents spend an average of no more than twelve hours per weekday (total of five weekdays) on inpatient service. If circumstances require that a resident perform in-house duties more than twelve hours in a particular day, his or her duty hours will be reduced the subsequent day in order to maintain an average of twelve hours per day. While on inpatient service, the resident is also on call during weekdays. The call is on a beeper from home. It is extremely unusual for fellowship residents to have to stay in the hospital overnight. In that unusual circumstance, the resident is excused from duties the next day. Residents are instructed to turn off their beepers when they leave the hospital, and they are not on call. This schedule allows the first-year resident who is on inpatient service a total of six days away from program duties during the four- week period. The average number of hours spent on in-house duties is sixty-four per week for a four-week period (sixty hours for five weekdays and sixteen hours every fourth weekend). During the first year of fellowship, when a resident is not on inpatient service, he or she is not on call during the weekdays but continues to be on call every fourth weekend for a total of sixteen hours in-house with the rest of his or her on-call duties to be performed from home, on a beeper as described above. During the second and third year of fellowship, residents have no weekday on-call service, except during the two months of inpatient pre-tending service during the third year. They continue to have on-call duties every fourth weekend as described above. 37. During the entire fellowship, residents have a total of six days away from program duties during the four-week period regardless of the type of rotation they are doing. General Fellowship Duty-Hour Policy per ACGME Guidelines To comply with ACGME guidelines, the Pediatric Hematology/Oncology Fellowship Program Director will monitor: Resident duty hours to assure that excessive fatigue or stress in the house officer does not adversely affect patient care Resident stress, including the possibility of mental or emotional condition, which might inhibit the performance of learning Time allocation to provide appropriate scheduling that permits participation in educational activities Distribution of policies to the residents and the faculty The Pediatric Hematology/Oncology Fellowship Program Director will also ensure that: Faculty and residents be educated to recognize the signs of fatigue and adopt and apply policies to prevent and counteract the potential negative effects Duty hours be limited to eighty hours per week averaged over a four-week period, inclusive of all in-house call activities (unless prior approval from the ACGME and GMEOC has been obtained to increase this amount to up to ten additional hours) Residents be provided with one day in seven free from all educational and clinical responsibilities, averaged over a four-week period, inclusive of call. One day is defined as one continuous twenty-four-hour period that is free from all clinical, educational, and administrative activities. Adequate time for rest and personal activities be provided. This should consist of a ten- hour time period provided between all daily duty periods and after in-house call. The Pediatric Hematology/Oncology Fellowship Program director will also ensure the following: In-house call must occur no more frequently than every third night, averaged over a four- week period. Continuous on-site duty, including in-house call, must not exceed twenty-four consecutive hours. Residents may remain on duty for up to six additional hours to participate in didactic activities, transfer care of patients, conduct outpatient clinics, and 38. maintain continuity of medical and surgical care as defined in Specialty and Subspecialty Program Requirements. No new patients, as defined in Specialty and Subspecialty Program Requirements, may be accepted after twenty-four hours of continuous duty. At-home call (pager call) is defined as call taken from outside the assigned institution. The frequency of at-home call is not subject to the every-third-night limitation. However, at-home call must not be so frequent as to preclude rest and reasonable personal time for each resident. Residents taking at-home call must be provided with one day in seven that is completely free from all educational and clinical responsibilities, averaged over a four- week period. When residents are called into the hospital from home, the hours that residents spend in- house are counted toward the eighty-hour limit. The program director and the faculty must monitor the demands of at-home call in their programs and make scheduling adjustments as necessary to mitigate excessive service demands and/or fatigue. 39. Fellowship Resident Moonlighting Policy The Department of Pediatrics adheres to ACGME moonlighting policies. As such, the department will assure that outside activities do not adversely affect a pediatric fellows primary responsibility to patients. No compromise of patients medical care shall occur by a pediatric resident to fulfill an outside activity obligation, and residents are expected to take into consideration patient load, reading, rotations, etc., when planning to schedule moonlighting activities so as not to compromise their capabilities. In addition, the department will ensure that moonlighting activities do not interfere with the ability of the resident to achieve the goals and objectives of the educational program. Residents must inform the House Staff Affairs Office and their Pediatric Residency program director of their outside activities. The Residency Program will comply with the institutions written policies and procedures regarding moonlighting, in compliance with the institutional requirements. If a pediatric resident chooses to participate in moonlighting activities, the program director will place a prospective written statement in that residents permanent file and monitor that residents performance for the effect of these activities upon performance. The House Staff Committee, a standing medical committee, is responsible for reviewing all alleged infractions of this policy if not resolved at the department level. Any hours a resident works for compensation at the sponsoring institution or any of the sponsors primary clinical sites will be considered part of the eighty-hour weekly limit on duty hours. This refers to the practice of internal moonlighting. 40. Faculty The faculty consists of eight board-certified pediatric hematologists/oncologists. Paul Sondel, MD, PhD: Dr. Sondel is the Chief of the Pediatric Hematology/Oncology Division. He is a nationally recognized, accomplished physician-scientist in translational research in molecular immunology and immunotherapy. He received numerous awards for his research accomplishments. Dr. Sondels work is well funded by two RO1 awards from the National Cancer Institute. His teaching role for our pediatric hematology/oncology fellows is threefold. First, as our other faculty, he is involved in direct one-on-one clinical teaching in the inpatient and outpatient settings. Second, he spends time with each fellow to discuss the interaction of lab science and clinical practice and helps fellows to identify research opportunities on our campus and participate in research seminars and journal clubs. Third, Dr. Sondel directly mentors pediatric hematology/oncology fellows during their basic science training in molecular immunology and gene therapy in his lab. Yousif Matloub, MD: Dr. Matloub is Clinical Director of the Pediatric Hematology/Oncology Division. He attends on the Pediatric Heme/Onc/HSCT service eleven weeks per year and runs oncology and HSCT clinics. Dr. Matloub typically gives two formal talks each week while attending and participates in informal teaching on the wards and in the clinics. He also organizes our Pediatric Heme/Onc Educational Conference, which is a weekly meeting that alternates between journal club, didactic talks covering various hematology, oncology, and transplant topics, and research presentations. He is nationally recognized for his expertise in Acute Lymphoblastic Leukemia (ALL) and clinical research training in ALL. Dr. Matloub is supported by the National Cancer Institute as a Childrens Oncology Group Principal Investigator. As a principal investigator, Dr. Matloub mentors fellowship residents in clinical investigation and provides guidance to fellowship residents in how to get more involved in COG sponsored clinical studies. Carol Diamond, MD: Dr. Diamond supervises the Coagulation Disorder and Hemophilia Center and also oversees the Sickle Cell Disease Clinic. Dr. Diamond served as the Pediatric Hematology/Oncology Fellowship Director from November 1999-July 2005. Currently she interacts with the residents when they attend her hematology clinics, while she is attending on service, and when they seek consultation regarding clinical hematology problems. Dr. Diamond supervises the hematology training course. As well, she works very closely with residents when they participate in teaching the hematopathology class as second-year medical students. Dr. Diamond is the Medical Director of the Pediatric Comprehensive Bleeding Disorders Program, Medical Director of Pediatric Specialties Clinic, Medical Director of the Pediatric Sickle Cell Program, Co- Director of the Pediatric Clerkship Program, and a member of the Resident Advisory Committee. In addition, Dr. Diamond is a very accomplished and experienced physician with a long-term commitment to pediatric hematology and clinical research in disorders of hemostasis. 41. Diane Puccetti, MD: Dr. Puccetti is the clinical director of the Pediatric Neuro-Oncology Clinic. Her teaching efforts focus on the comprehensive care of children with central nervous system tumors, general oncology issues, and the inpatient and outpatient treatment and follow-up of children with cancer. Dr. Puccetti has been a strong childrens advocate for many years while working as a faculty member at the University of Wisconsin. She provides valuable teaching experience that is centered on patients with brain tumors and terminally ill patients. She also organizes many End-of-Life Care conferences. Dr. Puccetti supervises Tumor Board Conferences, is Medical Editor of our patients newsletter, Medical Director of our Caring for Life (survivors) clinic, and faculty advisor for our Survivors Web site. Her clinical research in Neuro-Oncology includes a focus on brain tumors and long-term side effects of chemotherapy. Margo Hoover-Regan, MD: Dr. Hoover-Regan supervises the Palliative Care and End- of-Life Care rotation. She is actively involved in patient advocacy committees. She organizes and teaches the pediatric palliative care curriculum, teaches fellows and residents on work rounds and at the bedside, models effective communication skills in the context of patient care on the inpatient ward and in the clinic while seeing patients with fellows. Dr. Hoover-Regan gives lectures at regularly scheduled educational sessions within the pediatric hematology/oncology division, presents patient cases, and discusses diagnosis and treatment at weekly pediatric tumor board conferences. Her clinical research focus is in palliative care. Ken DeSantes, MD: Dr. DeSantes is Director of the Bone Marrow Transplant Program and an accomplished bone marrow transplant physician. He is developing innovative immune-based protocol for treatment of neuroblastoma. He is also developing a new Transplant Protocol for neuroblastoma patients. Midwest Athletes Against Childhood Cancer Foundation funds his research extramurally. His areas of interest include bone marrow transplant for neuroblastoma and non-ablative transplant regimens. Dr. DeSantes attends on the Pediatric Heme/Onc/HSCT service eleven weeks per year and runs oncology and HSCT clinics. He typically gives two formal talks each week while attending and participating in formal teaching on the wards and in the clinics. Dr. DeSantes also organizes the weekly Pediatric Heme/Onc Educational Conference. Dr. DeSantes provides valuable clinical and translational research experience and mentorship to Pediatric Hematology Oncology Fellowship Residents. Kaci Osenga, MD: Dr. Osenga joined our program in July 2005 as a Clinical Instructor following the completion of her fellowship residency and research project. The major interest of Dr. Osenga is palliative and end-of-life care. Together with Dr. Hoover-Regan, she organizes and teaches the pediatric palliative care curriculum. Dr. Osenga teaches fellows and residents on work rounds and at the bedside and gives lectures at regularly scheduled educational sessions within the pediatric hematology/oncology division. Sinisa Dovat, MD D.Sc: Dr. Dovat is Program Director of the University of Wisconsin Pediatric Hematology/Oncology Fellowship Program and Director of Molecular 42. Oncology Research at the Division of Pediatric Hematology/Oncology. He is a physician- scientist with major interests in molecular mechanisms of cellular proliferation and use of pharmacogenomics for treatment of childhood malignancies. For his research, Dr. Dovat received the Young Investigator Award by the American Society of Pediatric Hematology/Oncology in 2001. His research is funded by NIH/NCI through K-22 award, and other extramural grants. Dr. Dovat does direct, one-on-one clinical teaching of fellows during their inpatient and outpatient rotations. He mentors two current fellows in their research projects. He directs the Board Review Course and Introduction to Biomedical Research Course. As a program director, Dr. Dovat meets periodically with fellows to discuss potential problems and ways to improve fellowship training. Nurse Practitioners Sharon Frierdich Kris Chambas Kristin Casey Barbara Byrne Current Fellows David Delgado, MD Shannon Dean, MD John Hipps, MD, M.PH. Marcela Popescu, MD (Research Fellow) Application Process DEADLINE: March 15, 2007 Contacts Fellowship Director Sinisa Dovat, MD dovat@wisc.edu University of Wisconsin Childrens Hospital 600 Highland Avenue, Suite H4/426 CSC Madison, WI 53792-9988 (608) 263-8555 (phone) Fellowship Coordinator Sandy Rens sarens@wisc.edu University of Wisconsin Childrens Hospital 600 Highland Avenue Suite K4/438 CSC Madison, WI 53792-4672 43. (608) 263-6200 (phone)