Pediatric Hodgkin lymphoma– biomarkers, drugs, and clinical trials for translational science and medicine
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Poonam Nagpal1, Mohamed R. Akl1, Nehad M. Ayoub2, Tatsunari Tomiyama1, Tasheka Cousins1, Betty Tai1, Nicole Carroll1, Themba Nyrenda3, Pritish Bhattacharyya4, Michael B. Harris5, Andre Goy6, Andrew Pecora6 and K. Stephen Suh1,3
1 The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA
2 Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
3 Department of Research, Hackensack University Medical Center, Hackensack, NJ, USA
4 Department of Pathology, Hackensack University Medical Center, Hackensack, NJ, USA
5 Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA
6 Clinical Divisions, The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA
K. Stephen Suh, email:
Keywords: Hodgkin lymphoma, pediatric, adolescent, biomarker, tumor microenvironment
Received: March 23, 2016 Accepted: August 18, 2016 Published: August 22, 2016
Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging. Targeted HL therapy with the antibody-drug conjugate Brentuximab vedotin (Bv) has proven to be superior to conventional salvage chemotherapy and clinical trials are being conducted to incorporate Bv into frontline therapy that substitutes Bv for alkylating agents to minimize secondary malignancies. The appearance of secondary malignancies has been a concern in pediatric HL, as these patients are at highest risk among all childhood cancer survivors. The risk of developing secondary leukemia following childhood HL treatment is 10.4 to 174.8 times greater than the risk in the general pediatric population and the prognosis is significantly poorer than the other hematological malignancies with a mortality rate of nearly 100%. Therefore, identifying clinically valuable biomarkers is of utmost importance to stratify and select patients who may or may not need intensive regimens to maintain optimal balance between maximal survival rates and averting late effects. Here we discuss epidemiology, risk factors, staging, molecular and genetic prognostic biomarkers, treatment for low and high-risk patients, and the late occurrence of secondary malignancies in pediatric HL.
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