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Alix E. Seif, MD, MPH

Alix E. Seif, MD, MPH

Attending Physician

Assistant professor, University of Pennsylvania School of Medicine

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Expertise:

    Hematologic malignancies
    Blood and marrow transplantation

Extended Bio

Despite advances in treating pediatric acute lymphoblastic leukemia (ALL), children with relapsed disease have dismal outcomes and are often not curable with chemotherapy alone. Furthermore, children with residual leukemia cells after chemotherapy are highly likely to relapse. Simply adding more traditional chemotherapy will not treat chemotherapy-resistant cells and just adds toxicity; we are developing other approaches to eliminating chemoresistant ALL with the goal of improving efficacy and reducing toxicity.

We have shown that a drug that stimulates the immune system like a virus or bacteria does can cure ALL in mice, results leading to a national phase I/II pediatric clinical trial. This type of immune stimulation generates long-term immune memory like a vaccine does, allowing the immune system to recognize and kill residual leukemia cells long after the leukemia is in remission. Our current focus takes a novel two-pronged approach to enhance the immune system’s ability to kill ALL, combining our immune stimulant with drugs already in clinical use that make tumor cells more recognizable to the immune system. In addition, we have identified the largest group of pediatric ALL patients ever reported and will use this cohort to evaluate our findings in children with ALL who have had immune stimulation by infections.

Immune stimulation may help children with chemotherapy-resistant ALL and may improve efficacy of current therapies without adding new toxicity. Furthermore, if we stimulate a child’s immune system to recognize ALL, long-term memory effects may prevent relapse for his or her lifespan. We have compelling laboratory data that immune stimulation is effective; however, most treatments that work in the lab fail in clinical trials. Using existing data from a nationwide group of children with ALL, we can evaluate immune stimulation in children long before Phase III testing. This approach will also apply to other rare pediatric cancers, such as acute myeloid leukemia (AML).

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