Professor of Pediatrics, University of Pennsylvania School of Medicine
- Department: Pediatrics
- Division: Oncology
- Primary Address:
4308 Wood Building
The Chidrens Hospital of Philadelphia
34th and Civic Center Blvd.
Philadelphia, PA 19104
Interventional trials to improve cognition in chidlren with cancer; functional anatomy of radiation and chemotherapy injury; infection in the compromised host; clinical trials in childhood leukemia
- Emeritus Professor CE of Pediatrics, University of Pennsylvania School of Medicine (2012 – present)
- Professor of Pediatrics at the Children's Hospital of Philadelphia (1990 – 2012)
- Associate Professor of Pediatrics at the Children's Hospital of Philadelphia (1984 – 1990)
- Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine (1978 – 1984)
- M.D., Temple University (1971)
- A.B., History of Art, Cum laude, Bryn Mawr College, Bryn Mawr, Pennsylvania (1967)
My career in pediatric oncology began 35 years ago in the exhilarating times when we were just beginning to learn how to use combinations of anti-cancer drugs to prevent recurrence of childhood cancer and death from cancer. The enduring theme of my work has been to improve cure rate through better chemotherapy while reducing side effects. My personal goal and that of The Children's Hospital of Philadelphia is for cancer patients to emerge from cancer treatment as least as good as they were before their therapy. Central to the goal of reducing side effects has been reducing the amount of radiation therapy needed to cure a tumor by replacing radiation with chemotherapy.
Over this time I have had the opportunity to direct many clinical trials at Children's Hospital or in the major national pediatric oncology research group, the Children's Oncology Group (COG) -- and at the same time to collaborate with scientists to discover better treatments with less serious side effects. My first research trials were in Hodgkin's disease. More chemotherapy and less radiation showed improved cure rates and eliminated the problem of growth failure in irradiated areas and long surgical procedures needed to locate all possible areas of involvement in the abdomen. This approach is now used in most children and many adults with Hodgkin's disease.
By the early 1980s, my research extended to trials in leukemia and then to trials in brain tumors -- and continues in these areas today. Radiation of the brain has been responsible for improving cure rates in children with acute lymphoblastic leukemia (ALL), the most common childhood cancer, and in brain tumors, the most common childhood solid tumor. However, the higher the dose of radiation and the younger the child, the more severe the side effects. The most serious side effect is cognitive impairment, specifically, problems in paying attention and then remembering, thinking, planning and doing all these things relatively quickly.
Reducing and eventually eliminating radiation for younger children with leukemia has to a large extent reduced problems with learning. However, some children with leukemia still need brain irradiation -- and some of the chemotherapy used in leukemia also impairs cognition. Additionally, children with brain tumors often have learning problems from the tumors themselves.
Many cognitive problems don't become evident immediately, particularly in leukemia survivors: what may become a progressive problem first manifests itself two or three or more years after treatment. There have been some trials to improve established cognitive deficits using either stimulant medications or cognitive psychotherapy and working with the special educational system. The results have been modest and limited to small numbers of children. Thus cognitive impairment is the most important unsolved problem in the area of cancer treatment complications.
I am one of a growing group of investigators at Children's Hospital and in COG committed to reshaping the field of cognitive impairment. There is emerging evidence that cancer survivors with established cognitive problems also can benefit from systematic cognitive re-education. This re-education can be accomplished with computer-based cognitive remediation programs that involve parent and child participation at home or in the outpatient clinic, with oversight by a trained coach. We are currently developing supervised computer-based trials for children known to have problems. This can be done with relatively low cost and can be made available to almost all children. We are also planning trials to use computer-based programs to diagnose cognitive problems earlier -- allowing us an opportunity to train young minds before the problem occurs. Our hope is to treat the problem before it occurs.
Essentially, we are using the same paradigm as we used when we began to use chemotherapy before a cancer recurs.
- Horan John T, Alonzo Todd A, Lyman Gary H, Gerbing Robert B, Lange Beverly J, Ravindranath Yaddanapudi, Becton David, Smith Franklin O, Woods William G,. Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children's Oncology Group.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Vol 26(35) . 2008 Dec:5797-801.
- Sung Lillian, Alonzo Todd A, Gerbing Robert B, Aplenc Richard, Lange Beverly J, Woods William G, Feusner James, Franklin Janet, Patterson Maria J, Gamis Alan S,. Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.. Pediatric blood & cancer. Vol 51(6) . 2008 Dec:784-6.
- Aplenc Richard, Alonzo Todd A, Gerbing Robert B, Lange Beverly J, Hurwitz Craig A, Wells Robert J, Bernstein Irwin, Buckley Patrick, Krimmel Kathleen, Smith Franklin O, Sievers Eric L, Arceci Robert J,. Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Vol 26(14) . 2008 May:2390-3295.
- Orsey Andrea, Paessler Michele, Lange Beverly J, Nichols Kim E. Central nervous system juvenile xanthogranuloma with malignant transformation.. Pediatric blood & cancer. Vol 50(4) . 2008 Apr:927-30.
- Bhatla D, Gerbing R B, Alonzo T A, Mehta P A, Deal K, Elliott J, Meshinchi S, Geiger H, Perentesis J P, Lange B J, Davies S M,. DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group.. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. Vol 22(2) . 2008 Feb:265-72.
- Lange Beverly J, Smith Franklin O, Feusner James, Barnard Dorothy R, Dinndorf Patricia, Feig Stephen, Heerema Nyla A, Arndt Carola, Arceci Robert J, Seibel Nita, Weiman Margie, Dusenbery Kathryn, Shannon Kevin, Luna-Fineman Sandra, Gerbing Robert B, Alonzo Todd A. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group.. Blood. Vol 111(3) . 2008 Feb:1044-53.
- Castellino Sharon M, Alonzo Todd A, Buxton Allen, Gold Stuart, Lange Beverly J, Woods William G. Outcomes in childhood AML in the absence of transplantation in first remission--Children's Cancer Group (CCG) studies 2891 and CCG 213.. Pediatric blood & cancer. Vol 50(1) . 2008 Jan:9-16.
- Sung Lillian, Lange Beverly J, Gerbing Robert B, Alonzo Todd A, Feusner James. Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia.. Blood. Vol 110(10) . 2007 Nov:3532-9.
- Neudorf S, Sanders J, Kobrinsky N, Alonzo T A, Buxton A, Buckley J D, Howells W, Gold S, Barnard D R, DeSwarte J, Kalousek D, Lange B J, Woods W G. Autologous bone marrow transplantation for children with AML in first remission.. Bone marrow transplantation. Vol 40(4) . 2007 Aug:313-8.
- Butturini Anna M, Dorey Frederick J, Lange Beverly J, Henry David W, Gaynon Paul S, Fu Cecilia, Franklin Janet, Siegel Stuart E, Seibel Nita L, Rogers Paul C, Sather Harland, Trigg Michael, Bleyer W Archie, Carroll William L. Obesity and outcome in pediatric acute lymphoblastic leukemia.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Vol 25(15) . 2007 May:2063-9.