New drug cuts risk of deadly transplant side effect in half

December 2, 2013

A new class of drugs reduced the risk of patients contracting a serious and often deadly side effect of lifesaving bone marrow transplant treatments, according to a study from researchers at the University of Michigan Comprehensive Cancer Center.

The study, the first to test this treatment in people, combined the drug vorinostat with standard medications given after transplant, resulting in 22 percent of patients developing graft-vs.-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone. Results of the study appear in The Lancet Oncology.

"Graft-vs.-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says lead study author Sung Choi, M.D., assistant professor of pediatrics at the U-M Medical School.

Vorinostat is currently approved by the U.S. Food and Drug Administration to treat certain types of cancer. But U-M researchers, led by senior study author Pavan Reddy, M.D., found in laboratory studies that the drug had anti-inflammatory effects as well – which they hypothesized could be useful in preventing graft-vs.-host disease, or GVHD, a condition in which the new donor cells begin attacking other cells in the patient's body.

The study enrolled 61 older adults from the University of Michigan and Washington University in St. Louis who were undergoing a reduced-intensity with cells donated from a relative. Patients received standard medication used after a transplant to prevent GVHD. They also received vorinostat, which is given as a pill taken orally. Fifty of the 61 participants completed the full 21-day course of vorinostat.

The researchers found vorinostat was safe and tolerable to give to this vulnerable population, with manageable side effects. In addition, rates of patient death and cancer relapse among the study participants were similar to historical averages.

The results mirror those found in the laboratory using mice. Reddy, the Moshe Talpaz Professor of Oncology and professor of internal medicine at the U-M Medical School, has been studying this approach in the lab for eight years.

"This is an entirely new approach to preventing graft-vs.-host disease," Reddy says. Specifically, vorinostat targets histone deacetylases, which are different from the usual molecules targeted by traditional treatments.

"Vorinostat has a dual effect as an anti-cancer and an anti-inflammatory agent. That's what's potentially great about using it to prevent graft-vs.-host, because it may also help prevent the leukemia from returning," says Reddy, who is also co-director of the hematologic malignancies and transplant program at the U-M Comprehensive Cancer Center.

"We are encouraged by our findings," Choi says. "Vorinostat combined with standard prophylaxis after related-donor transplant appears to be safe and associated with lower than expected incidence of acute GVHD. Future studies are needed to assess the effect of vorinostat in broader transplant settings. We are currently investigating vorinostat plus standard therapies to prevent GVHD in transplants with an unrelated donor."

Explore further: New drug cuts risk of deadly transplant side effect in half

More information: Reference: The Lancet Oncology, published online Nov. 30, 2013

Related Stories

New drug cuts risk of deadly transplant side effect in half

December 9, 2012
A new class of drugs reduced the risk of patients contracting a serious and often deadly side effect of lifesaving bone marrow transplant treatments, according to a study from researchers at the University of Michigan Comprehensive ...

Targeting histone deacetylases as a new strategy for graft versus host disease prevention

December 9, 2012
New research shows that the addition of the oral anti-cancer agent vorinostat to standard therapy given before, during, and after hematopoietic stem cell transplantation (HSCT) may safely reduce the incidence and severity ...

Newly identified proteins make promising targets for blocking graft-vs-host disease

October 31, 2013
Researchers from the University of Michigan Comprehensive Cancer Center have identified new proteins that control the function of critical immune cell subsets called T-cells, which are responsible for a serious and often ...

Mystery explained: How a common chemo drug thwarts graft rejection in bone marrow transplants

November 13, 2013
Results of a Johns Hopkins study may explain why a chemotherapy drug called cyclophosphamide prevents graft-versus-host (GVHD) disease in people who receive bone marrow transplants. The experiments point to an immune system ...

Natural enzyme provides potential new approach for treating graft-vs-host disease

January 17, 2012
A natural enzyme derived from human blood plasma showed potential in significantly reducing the effects of graft-vs.-host disease, a common and deadly side effect of lifesaving bone marrow transplants.

Certain types of graft-versus-host disease may increase risk of death, researcher says

June 17, 2013
Joseph Pidala, M.D., M.S., assistant member of the Blood and Bone Marrow Transplant and Immunology programs at Moffitt Cancer Center, and colleagues from the Chronic Graft-Versus-Host Disease Consortium have determined that ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.