Drug duo prevents life-threatening condition in children undergoing stem cell transplant

A drug duo appears to be a safe and effective way to prevent a serious condition called graft-versus-host-disease (GVHD) in youngsters undergoing a stem cell transplant, researchers from Children’s Hospital of NewYork-Presbyterian/Columbia University Medical Center report in the April 13 issue of the journal Biology of Blood and Marrow Transplantation. GVHD is a common condition in which the transplanted cells attack the recipient’s tissue. It can cause a skin rash, enlarged liver and intestinal problems including diarrhea. In the worst cases, the skin can blister and peel over the entire body. Immune-suppressing drugs can halt GVHD but also leave the recipient vulnerable to infection.

Two drugs are often used as a prophylactic treatment to prevent the condition – methylprednisolone, a powerful immune system-suppressing drug, and methotrexate, an antirejection drug. However, both drugs can have side effects. Methylprednisolone can cause glucose intolerance (a precursor to diabetes) and high blood pressure. Methotrexate can exacerbate treatment-related mouth ulcers, as well as have a toxic effect on the liver and kidneys.

“While these drugs are 20 percent to 50 percent effective at preventing acute GVHD in children undergoing a stem cell transplant, they can also cause damage to the organs, including the kidney and liver,” said Dr. Mitchell S. Cairo, professor of pediatrics, medicine and pathology at Columbia University College of Physicians & Surgeons and chief of the Division of Pediatric Hematology and Blood and Marrow Transplantation at Children’s Hospital of NewYork-Presbyterian.

“We wanted to find a safer alternative for these youngsters,” said Dr. Cairo, who is also the director of the Leukemia, Lymphoma and Myeloma Program at the Herbert Irving Comprehensive Cancer Center.

In the study, Dr. Cairo and his colleagues tried two drugs – a new, more potent immune-suppressing drug called tacrolimus (FK506) and a second immune system-suppressing drug called mycophenolate mofetil (MMF). While sometimes used to treat adults with GVHD when other drugs fail, the researchers tried the combination as a prophylactic measure to prevent GVHD in 34 children and adolescents.

“While these drugs can have side effects too, we hoped they would be less toxic for these seriously ill children and still prevent GVHD,” said Dr. Cairo. “Depending on how well matched donor and recipient are, anywhere from 40 percent to 80 percent of transplant patients can develop GVHD.”

The children, who were a median age of 7, were undergoing a transplant due to cancer or blood disorders. The children received donor stem cells from umbilical cord blood or the bone marrow or blood of relatives. All were treated with FK506 and MMF.

Overall, the researchers found there was a 45 percent probability of developing acute (within 100 days of transplant) GVHD and a 34 percent probability of developing chronic (100 days or more after transplant) GVHD.

“The combination of FK506 and MMF may be equivalent or better than other drug treatments when it comes to preventing GVHD,” said Dr. Cairo.

“However, if this side effect occurs reducing the dose or stopping the drug altogether often causes symptoms to resolve,” said Dr. Cairo. “Even with this potential side effect, the drug combination may be less toxic overall than other drug combinations.”

The results are encouraging and warrant a study in which FK506/MMF is compared head-to-head with other drug combinations for the prevention of GVHD, said Dr. Cairo.

“FK506/MMF appears to be well tolerated, but more study is needed to determine if it is a safe and effective way to prevent GVHD while avoiding drugs such as methotrexate and methylprednisolone,” he concluded.

The study was supported in part by grants from the Pediatric Cancer Research Foundation, the Pediatric Cancer Foundation and the Swim Across America Foundation.