Dr. Joanna Perkins is a pediatric hematologist/oncologist at Children’s Hospitals and Clinics of Minnesota in Minneapolis. She joined the professional staff at Children’s in September, 2003 after completing her fellowship in pediatric hematology/oncology/BMT at the University of Minnesota. She also received her bachelor’s degree in psychology, her doctorate from the School of Medicine, and her master’s degree in clinical research at the University of Minnesota. Her research has focused on the long-term effects of treatment for childhood cancer. She lives with her husband Ron and two sons (Alex and Nick) in Apple Valley.

The immune system is the term used to describe the human body’s very complex system of blood cells and proteins that fight various types of infection. These blood cells and proteins are produced in the bone marrow and lymph node tissues throughout the body. The immune system is also responsible for making protective proteins, called antibodies, in response to infection or immunization. Problems with the immune system can be “primary”, meaning a person is born with a deficiency in some component of the system, or “secondary”, meaning the deficiency is caused by something after birth.

Children with cancer have secondary immune deficiencies as a result of their underlying disease and due to the chemotherapy and/or radiation treatments they receive. Chemotherapy and radiation therapy temporarily destroy the cells of the immune system, placing children at a much higher risk for infection. It is not clear, however, which components of the immune system are most affected, how severely they are impaired, or how long following completion of treatment they remain immune compromised. Previous researchers generally agree that by six months after treatment, most patients have recovered immune function. However, we know that some patients may remain abnormal months to years after completing treatment and continue to be at higher risk for infection than other children their age.

We know from isolated cases that following treatment for cancer, some children lose their protection against diseases for which they have previously been vaccinated. One example is a patient who had AML, a type of childhood leukemia. More than one year after finishing treatment, she became ill with mumps. This is a disease for which she had previously been vaccinated. When her protective antibody titers for mumps and other childhood diseases were checked, she had lost protection to all diseases she had previously been immunized against. One year off therapy, most children with cancer have immune function similar to healthy children. However, for many children blood counts may still be persistently low, which may be associated with increased risk for infection. In addition, even when these children are re-immunized, their response to the vaccines is not always protective. Currently, there are no standard recommendations for checking antibody titers, re-immunizing children following cancer treatment, nor for testing post-vaccine titers to verify protection against these diseases.

We know children receiving chemotherapy and/or radiation therapy are at risk for a specific type of pneumonia, pneumocystis carinii pneumoniae (PCP). We administer preventative antibiotics during treatment, and usually for 3-6 months after completing treatment. However, there are no uniformly accepted guidelines for how long to continue this antibiotic therapy.

The few previous studies in this area have been limited by small numbers of patients, and by lack of comprehensive immune system evaluation. There is a great need to define what infectious risks these children face after completing treatment for cancer, in order to develop standardized approaches to off-therapy preventative antibiotics and re-immunization schedules.

Study Design: The proposed study design is a prospective, single institution cohort study. This study will include all children with cancer diagnosed prior to 21 years of age, to be enrolled when they are at the end of their therapy. Patients who have a known preceding primary immune deficiency or have had stem cell transplantation will be excluded. Following recruitment and consent to participate, the following laboratory data will be collected at end of therapy, 3 months off therapy, 6 months off therapy, 9 months off therapy, and 1 year off therapy: complete blood counts (CBC), immune globulins (IgG, IgM, IgA, IgE), T- and B-lymphocyte profile, lymphocyte function, NK cell function, and vaccine titers (Varicella, DPT, MMR, Polio, Hepatitis B Surface Antibody, Hepatitis A Antibody, and Pneumococcus). For patients who are found to be non-immune to previously vaccinated diseases, re-immunization will be implemented and follow-up titers continued according to the study schedule.

Statistical Section: The primary outcome measure used to assess the study goals is any impairment in immune function. A patient’s treatment will be categorized as low, intermediate, or high intensity based on the doses of chemotherapy and/or radiation therapy. If a child has one or more abnormal lab values, they will be classified as having impaired immune function.

The hypotheses include:

1) Patients who receive high intensity treatment will have significantly higher loss of immunity to previous vaccinations/illnesses (e.g. chicken pox) and impaired immune function than patients who receive low or intermediate intensity treatment.

2) Abnormalities in immune function will be documented and will continue to be present greater than 6 months off therapy for some patients.

Importance of Research: The Hope on Wheels Award funds will be used in part to cover the cost of laboratory testing for the patients. Because there are no accepted guidelines for who needs testing or when, these laboratory studies would not generally be covered by medical insurance. As a result of the data gathered from this study, The Hope on Wheels Hyundai Scholar Award will allow me to begin to define what group(s) of patients continue to have impaired immune systems following cancer treatment, and for how long this impairment continues. This will enable pediatric oncologists to develop evidence-based guidelines for which patients need to be re-immunized and for how long we need to continue to give these children preventative antibiotics against PCP pneumonia.

Professional Development: In addition to the cost of research testing, the Hope on Wheels Award funds will be used for my educational advancement in the area of immunology . My fellowship training and board certification is in pediatric hematology and oncology. My area of research interest is the study of late effects of childhood cancer treatment. One of the most important late effects these children face is immune deficiency and risk for infection. Expanding my scientific background and understanding of the field of immunology and immune deficiencies by attending educational conferences/coursework in this area will strengthen my ability to continue to perform this research and improve on the quality of life for childhood cancer survivors.

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