Why a secondary cancer after transplant? Grant may help find clues

December 11, 2013 | by

Myelodysplastic syndrome, once known as “preleukemia,” is a disease of the blood and bone marrow that often attacks people who have survived initial cancer treatment. “Good Morning America” co-host Robin Roberts, for example, was diagnosed with the syndrome, known as MDS, in June 2012, five years after successfully undergoing treatment for breast cancer. She’s one of an estimated 12,000 Americans who are diagnosed with the syndrome each year.

DNA analysis

Smita Bhatia and Ravia Bhatia, researchers at City of Hope, have received a grant from the V Foundation for Cancer Research to study MDS. They'll be using genomic tools to analyze mutations in DNA, as well as gene expression.

Two City of Hope researchers in particular are probing why patients who have undergone bone marrow transplants for lymphoma and other diseases are also vulnerable to being diagnosed with this deadly secondary cancer: Ravi Bhatia, M.D., director of the Division of Hematopoietic Stem Cell and Leukemia Research at City of Hope, and Smita Bhatia, M.D., M.P.H., the Ruth Ziegler Chair in Population Sciences and the co-leader of the Cancer Control and Population Sciences Program.

Now, the Bhatias have received a $600,000 grant over a three-year period from the V Foundation for Cancer Research to study why the disease develops and devise ways to treat and prevent this lethal complication.

“We are trying to understand the underlying mechanisms of how patients who have undergone successful treatment for lymphoma develop therapy-related leukemia,” Smita Bhatia explained.

“This is a brand-new cancer that develops in patients who have been treated for lymphoma or other diseases after getting an autologous transplant [in which a patient receives an infusion of his or her own purified stem cells]. And unfortunately," she added, "unless it is treated with yet another transplant, such as an allogeneic transplant from another sibling or some unrelated donor, it can be fatal."

“We’re trying to understand the molecular basis for the development of treatment-related myelodysplasia,” said Ravi Bhatia. Toward that end, they’ll be studying samples from patients who develop myelodysplasia after autologous transplant for lymphoma, and comparing them with samples from patients who do not develop this complication.

The Bhatias will analyze the samples using state-of-the-art genomic approaches (studying mutations in DNA, epigenetic changes in chromatin, and gene expression) to try to understand the molecular underpinnings for this disease.

Thanks to the study’s design, they will be able to identify changes that take place several months to several years before leukemia develops.

“The hope is that by studying this and understanding these changes, we will be able to identify patients who are at risk for developing this complication so we can offer them alternative treatments or preventive measures,” Ravi Bhatia said. “In addition, understanding the molecular basis for MDS development will allow us to design new treatments to try and either prevent MDS or to treat MDS.

“The funding from the V Foundation is absolutely essential for us to be able to conduct these studies,” he added.

The grant was part of $10.8 million awarded this year by the V Foundation for Cancer Research to 30 researchers and scientists nationwide.