Category: Research Publications

Lymphoma in the News: Family History May Be a Risk Factor for Non-Hodgkin Lymphoma

By Peter Martin, MD

A recently published study from investigators at Stanford University and in Lund University in Sweden used data from a large Swedish cohort study, birth records, and cancer registries to look for risk factors associated with development of non-Hodgkin lymphoma (NHL). The investigators evaluated the records of over 3.5 million people, including 936 with NHL, born between 1973 and 2008.

They reported that family history of NHL was associated with development of NHL in early life. Specifically, history of NHL in a sibling increased the risk of developing NHL roughly nine-fold while having a parent with NHL increased the risk of NHL roughly two-fold. Importantly, the overall incidence rate of NHL was 1.4 per 100,000 person-years (the number of people x the number of years of follow-up per person). Therefore, a two-fold increase, although statistically significant, would only have increased the rate to roughly 3 per 100,000 person years. Moreover, only 4 of the 936 cases had a sibling with NHL and 10 had a parent with NHL.

These small numbers, although statistically significant, make it difficult to make any definitive conclusions regarding the degree of risk. The lack of data regarding environmental exposures, infections, and other co-existing conditions (e.g., immunodeficiencies) make it difficult to determine whether the familial association of NHL is due to an inherited condition or some other unmeasured factor. Despite the issues, the results are consistent with the concept that genetic factors may contribute to NHL. It is possible that contemporary studies using next generation sequencing of the genomes of patients and family members could yield more conclusive results. The risks and benefits of such studies, however, need to be weighed very carefully.

PD0332991 Shows Promising Signs of Activity in Mantle Cell Lymphoma in Phase 1 Trial at Weill Cornell

By Peter Martin, MD

Cancer cells in mantle cell lymphoma (MCL) undergo uncontrolled proliferation due to overproduction of the protein Cyclin D1. The family of proteins called Cyclins combine with enzymes called Cyclin dependent kinases (Cdk) in a way that is analgous to gas in an engine. The Cdks are the engine but they rely on the Cyclins to make them work.

PD0332991 is an orally bioavailable (i.e., a pill) inhibitor of Cdk4/6, the Cdks that combine with Cyclin D1 in MCL. A recently published clinical trial  performed at Weill Cornell Medical College and other sites around the United States demonstrated that PD0332991 could successfully stop MCL tumors from growing in several patients, including one response that lasted for more than 30 months. Biopsies taken from patients while receiving PD0332991 revealed that Cdk4/6 was effectively inhibited while a specialized kind of imaging, called FLT-PET, demonstrated that MCL cells had stopped proliferating. Although these results were promising, not every patient benefited, and the responses were not permanent.

Additional studies combining PD0332991 with other drugs based on promising laboratory data are currently underway at Weill Cornell. Click here for more information.

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