Pediatric Oncology Care Research

Pediatric Oncology Care Research | CPCE

Oncology care and survivorship research at CPCE focus on improving the outcomes of pediatric cancer patients by investigating and identifying ways to improve treatment. Through research into variation of care across institutions, genetic predictors of treatment responses, and risk factors for treatment complications, this work can provide invaluable education to pediatric oncologists.

Treatment of Acute Myeloid Leukemia

Long-term Effects in Pediatric Patients after Cancer Therapy

Oncology Care Published Research

Treatment of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that affects immature blood cell growth. The second most common form of leukemia in children, AML is found throughout the bloodstream or in an organ, and must be treated aggressively as soon as possible after diagnosis.

Led by Richard Aplenc, MD, PhD, MSCE, CPCE’s research efforts in this area aim to improve the outcomes of children with cancer, particularly AML, by determining the genetic predictors of treatment response (specifically relapse and infection risk) and studying the clinical epidemiology of risk factors for treatment complications and outcome disparities using administrative data sets, particularly focusing on disparities in outcomes and antibiotic and intensive care resource utilization.

Several studies have addressed clinically significant research questions by merging data from the Children’s Oncology Group (COG) clinical trials with an external administrative/billing data set (Pediatric Health Information System—PHIS). COG is the largest international pediatric cooperative oncology group, and enrolls approximately 4,400 patients annually in therapeutic trials.

In this line of research, we have utilized COG/PHIS data to determine that patients with newly diagnosed pediatric leukemia who are admitted to the hospital on weekends have a prolonged length of stay, increased time to chemotherapy and higher risk for respiratory failure than those admitted during the week.

Additionally, CPCE research found that the use of chemotherapy regimen ADE, as opposed to an alternative called DCTER, is associated with lower induction mortality in pediatric AML.

These COG/PHIS merged data have also revealed that acute renal failure (ARF) is relatively common in children with AML and the risk for ARF is greater in older patients, in African-American patients, and in patients with increased exposure to the antibiotics vancomycin and carbapenem.

Further, research efforts in this area of pediatric oncology education have led to the understanding that adverse events are underreported in clinical trials.

See the Published Research

Funding:  National Institute of Health, Alex’s Lemonade Stand

Please contact Richard Aplenc, MD, PhD, MSCE, CHOP Attending Physician, for more information about this line of research.

Long-term Effects in Pediatric Patients after Cancer Therapy

Cancer therapy during childhood including chemotherapy and/or radiation can result in long-term late effects and chronic health conditions, which require prompt diagnosis, treatment and management following completion of cancer therapy.

CPCE researchers are studying the long term late effects of cancer therapy including hematopoietic stem transplantation (HSCT) on pediatric patients with benign and malignant hematologic disorders. Previous studies have shown that allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity which can contribute to long term metabolic treatment effects such as diabetes mellitus and cardiovascular mobidity.

Additional clinical studies in this research program revealed that pediatric cancer survivors treated with alloHSCT and total body irradiation demonstrated significantly compromised bone health placing them at greater risk for compression fractures.  In addition, survivors exhibited markedly increased adiposity with fat distribution within the bone marrow, viscera, muscles, and subcutaneous regions.  These patients demonstrate sarcopenic obesity, insulin resistance and evolving metabolic complications that places them at increased future risks of morbidity and mortality.

See the Published Research

What's Next: Future studies will continue to focus on identification of strategies to prevent and treat metabolic and skeletal complications in growing numbers of childhood cancer survivors.

Funding: National Cancer Institute, Children’s Oncology Group, St. Baldrick’s foundation, Cannuso foundation, CHOP Foerderer Grant

Please contact Sogol Mostoufi-Moab, MD, MSCE, CHOP Attending Physician, for more information about this line of research.

Pediatric Oncology Care Published Research

Treatment of Acute Myeloid Leukemia

Aplenc R., Fisher BT, Huang Y S, Li Y, Alonzo TA, Gerbing RB, Hall M, Bertoch D, Keren R, Seif AE, Sung L, Adamson PC, Gamis A. Merging of the National Cancer Institute-funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group. Pharmacoepidemiol Drug Saf. 2012 May;21(2):37-43.

Fisher BT, Kavcic M, Li Y, Seif AE, Bagatell R, Huang YS, Zaoutis T, Torp K, Leckerman KH, Aplenc R. Antifungal prophylaxis associated with decreased induction mortality rates and resources utilized in children with new-onset acute myeloid leukemia. Clin Infect Dis. 2014 Feb;58(4):502-8.

Fisher BT, Zaoutis TE, Leckerman KH, Localio R, Aplenc R. Risk factors for renal failure in pediatric patients with acute myeloid leukemia: a retrospective cohort study. Pediatr Blood Cancer. 2010 Oct;55(4):655-61.

Goodman EK, Reilly AF, Fisher BT, Fitzgerald J, Li Y, Seif AE, Huang YS, Bagatell R, Aplenc R. Association of weekend admission with hospital length of stay, time to chemotherapy, and risk for respiratory failure in pediatric patients with newly diagnosed leukemia at freestanding U.S. children's hospitals. JAMA Pediatr. 2014 Oct;168(10):925-31.

Kavcic M, Fisher BT, Li Y, Seif AE, Torp K, Walker DM, Huang YS, Lee GH, Tasian SK, Vujkovic M, Bagatell R, Aplenc R. Induction mortality and resource utilization in children treated for acute myeloid leukemia at free-standing pediatric hospitals in the United States. Cancer. 2013 May;119(10):1916-23. 

Kavcic, M, Fisher BT, Seif AE, Li Y, Huang YS, Walker D, Aplenc R. Leveraging administrative data to monitor rituximab use in 2875 patients at 42 freestanding children's hospitals across the United States. J Pediatr. 2013 Jun;162(6):1252-8.

Maude SL, Fitzgerald JC, Fisher BT, Li Y., Huang YS, Torp K, Seif AE, Kavcic M, Walker DM, Leckerman KH, Kilbaugh TJ, Rheingold SR, Sung L, Zaoutis TE, Berg RA, Nadkarni VM, Thomas NJ, Aplenc R. Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States. Pediatr Crit Care Med. 2014 Feb;15(2):112-20.

Miller TP, Troxel AB, Li Y, Huang YS, Alonzo TA, Gerbing RB, Hall M, Torp K, Fisher BT, Bagatell R, Seif AE, Sung L, Gamis A, Rubin D, Luger S, Aplenc R. Comparison of administrative/billing data to expected protocol-mandated chemotherapy exposure in children with acute myeloid leukemia: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2015 Jul;62(7):1184-9.

Seif AE, Walker DM, Li Y, Huang YS, Kavcic M, Torp K, Bagatell R, Fisher BT, Aplenc R. Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients. Pediatr Blood Cancer. 2015 Apr;62(4):704-9.

Walker DM, Fisher BT, Seif AE, Huang YS, Torp K, Li Y, Aplenc R. Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid leukemia from 1999 and 2009: analysis of a national cohort of patients in the Pediatric Health Information Systems database. Pediatr Blood Cancer. 2013 Apr;60(4):616-20.


Long-term Effects in Pediatric Patients after Cancer Therapy

Mostoufi-Moab S, Seidel K, Leisenring WM, Armstrong GT, Oeffinger KC, Stovall M, Meacham LR, Green DM, Weathers R, Ginsberg JP, Robison LL, Sklar CA. Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol. 2016 Jul 5.

Noyes JJ, Levine MA, Belasco JB, Mostoufi-Moab S. Premature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after cis-Retinoic Acid Therapy in Medulloblastoma: A Case Report. Horm Res Paediatr. 2016;85(1):69-73.

Baker JF, Von Feldt JM, Mostoufi-Moab S, Kim W, Taratuta E, Leonard MB. Insulin-like Growth Factor 1 and Adiponectin and Associations with Muscle Deficits, Disease Characteristics, and Treatments in Rheumatoid Arthritis. J Rheumatol. 2015 Nov;42(11):2038-45.

Kovatch KJ, Bauer AJ, Isaacoff EJ, Prickett KK, Adzick NS, Kazahaya K, Sullivan LM, Mostoufi-Moab S. Pediatric Thyroid Carcinoma in Patients with Graves' Disease: The Role of Ultrasound in Selecting Patients for Definitive Therapy. Horm Res Paediatr. 2015 Apr 15.

Mostoufi-Moab S, Magland J, Isaacoff EJ, Sun W, Rajapakse CS, Zemel B, Wehrli F, Shakdar K, Baker J, Long J, Leonard MB. Adverse Fat Depots and Marrow Adiposity Are Associated with Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation. J Bone Miner Res 30(9):  1657-66, 2015.

Mostoufi-Moab S, Isaacoff EJ, Spiegel D, Gruccio D, Ginsberg JP, Hobbie W, Shults J, Leonard MB. Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy. Pediatr Blood Cancer 60(11): 1766-71, 2013. 

Tsampaliero A, Gupta PA, Denburg MR, Shults J, Zemel B, Mostoufi-Moab S, Wetzsteon R, Herskovitz R, Whitehead KM, Leonard MB. Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome. J Bone Miner Res 28(3): 480-8, 2013.

Mostoufi-Moab S, Barakat LP, Bauer AJ. Quality of life in adolescent patients with differentiated thyroid cancer: Moving beyond survival. J Clin Endocrinol Metab 97(10): 3453-6, 2012.