Non-Hodgkin lymphoma (NHL) ranks 5th in cancer incidence and cancer-related deaths, and is the second fastest growing cancer. In 2008, the American Cancer Society estimates that 66,120 Americans will be newly diagnosed (35,450 men and 30,670 women), while 19,160 Americans will die from this cancer (9,790 males and 9,370 women). In addition, NHL is the most commonly occurring hematological cancer, and tends to affect older adults (61% were age > 60 years). Although there is great clinical heterogeneity among the different histologic subtypes, most patients with advanced stage NHL and many patients with limited stage are good candidates for systemic chemotherapy for a variety of indications. For patients with diffuse large B-cell lymphoma, there is usually a compelling rationale for anthracycline-based chemotherapy, however, in the community less than half of older lymphoma patients receive it.

Holden Comprehensive Cancer Center Member and Pharmacy Faculty, DJ Murry and colleagues were recently awarded a grant through the SEER Rapid Response Surveillance Studies (RRSS) mechanism to investigate related questions. The study known as the Population-Based Lymphoma Pharmacosurveillance Study, or by the alternate name of Living with Lymphoma, will demonstrate the feasibility and potential value of a comprehensive data system for applying pharmacogenomics knowledge to population research. Hypotheses about clinical and molecular predictors of doxorubicin treatment choice, toxicity and response in patients with lymphoma will provide a useful test case. This will be a prognostic cohort study with nine-month follow-up for response, myelotoxicity, short-term neurocognitive abilities and physical function (frailty). Subjects will be Iowa residents age 45 and older who are newly diagnosed with any stage diffuse large B-cell or grade 3 follicular lymphoma during November 2008-July 2009, rapidly ascertained using electronic pathology. DNA will be extracted from saliva kits and SNPs in genes of interest evaluated using pyrosequencing. The research team hopes to begin enrolling individuals into the study in December 2008.

This study is a proof-of-principle study which will hopefully lead to a larger study in the future. Such studies could lead to the ability to individualize drug therapy by identifying single nucleotide polymorphisms (SNPs) in genes in the doxorubicin metabolic pathway or in genes involved in neurocognition. The knowledge gained about clinical and molecular predictors of doxorubicin treatment toxicity and response could provide new approaches to the clinical management of lymphoma patients in community practice. Collaborators include: the HCCC Population Data Research Core, the HCCC Biostatistics Core, the Iowa Cancer Registry, Natalie Denburg PhD, and Brian Link MD, and Paul Romitti PhD.