Advanced stage Hodgkin lymphoma (HL) is usually cured. However, there remains an important fraction of patients who fail therapy, and others who develop late, sometimes fatal, complications of therapy. An intensive treatment regimen results in a higher up front cure rate but at the cost of more second malignancies, fertility loss, and other long-term toxicities. There is a less intensive regimen that yields fewer upfront cures, fewer second malignancies, less fertility loss and fewer long-term toxicities. After taking the result of salvage therapies into account, the approaches generate very similar long term overall survival. If it were possible to target only high risk patients to the more intensive therapy, the upfront cure rate associated with the more intensive therapy might be maintained, while the second malignancies and other toxicities might be minimized in those patients not treated intensively. Our focus in this pilot application is to evaluate previously identified blood-based molecular markers as predictors of response and outcome in patients with advanced HL. We seek to extend the evaluation of molecular markers to include early time points that might be most helpful in guiding decisions about therapy. The markers to be studied will include EBV DNA, sCD30, TARC, sCD163 and sBLyS. We also will evaluate an EBV DNA assay refinement that we anticipate will diminish the noise associated with standard measurements in cell-free blood. The proposed studies will be carried out in the context of a large randomized cooperative group study (E2496) comparing ABVD and Stanford V. The study is complete, clinical and pathologic annotation, and long term outcomes are available.

Public Health Relevance

Hodgkin lymphoma treated with more intensive treatments is very likely to result in cure but can also lead to secondary cancers and other late toxic effects. Less intensive treatments are less likely to result in cure but are also associated with fewer secondary cancers and other late toxic effects. In this proposal, we will investigate blood tests that have been identified as promising to distinguish these two groups of patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA188824-01
Application #
8771661
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Jessup, John M
Project Start
2014-08-15
Project End
2016-07-31
Budget Start
2014-08-15
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$241,714
Indirect Cost
$90,451
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Kosowicz, John G; Lee, Jaeyeun; Peiffer, Brandon et al. (2017) Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation. J Virol 91:
Welch, Jennifer J G; Schwartz, Cindy L; Higman, Meghan et al. (2017) Epstein-Barr virus DNA in serum as an early prognostic marker in children and adolescents with Hodgkin lymphoma. Blood Adv 1:681-684
Kanakry, Jennifer A; Hegde, Aparna M; Durand, Christine M et al. (2016) The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases. Blood 127:2007-17
Crane, Genevieve M; Samols, Mark A; Morsberger, Laura A et al. (2016) Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived. PLoS One 11:e0163559