Advances in Stem Cell Research Techniques and New Transplant Strategies Reveal Opportunities for Improved Patient …

ATLANTA, Dec. 9, 2012 /PRNewswire-USNewswire/ -- Studies of stem cell biology and transplant approaches presented today at the 54th Annual Meeting of the American Society of Hematology (ASH) illustrate how the use of advanced modeling techniques is optimizing stem cells to treat patients with blood disorders, as well as the potential of enhanced treatment strategies to improve the success rate of hematopoietic stem cell (HSC) transplantation for these patients.

Hematopoietic stem cell transplantation is effectively used today as a form of "replacement" therapy for patients with hard-to-treat blood conditions, providing healthy HSCs to help patients whose bodies cannot properly fight infection or disease on their own. While transplants often lead to long-term remission for many patients, researchers are now challenging traditional assumptions in an effort to further improve success rates while minimizing the remaining risks associated with transplantation.

"As we learn more about the biology and therapeutic use of hematopoietic stem cells to cure blood disorders, we are able to refine our traditional approaches to reduce complications and deliver better patient benefits," said Vanderson Rocha, MD, PhD, moderator of the press conference and Professor of Hematology of Oxford University, United Kingdom. "We are finding that hematopoietic stem cells can be programmed in ways we previously did not think possible, a discovery that may lead to the development of important new therapeutic strategies."

This press conference will take place on Sunday, December 9, at 10:00 a.m. EST.

Targeting Histone Deacetylases as a New Strategy for Graft Versus Host Disease Prevention [Abstract 740]

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 of a challenging complication called graft-versus-host disease (GVHD).

HSCT is the primary form of treatment for many patients with blood disorders; it involves the transplantation of healthy blood-forming stem cells from the bone marrow, circulating blood, or umbilical cord blood to replace damaged, disease-causing cells in recipients. Despite the therapeutic benefits of HSCT, half of all patients who receive transplants from a related donor (allogeneic HCT) develop acute GVHD, a life-threatening condition occurring when the newly transplanted cells identify the recipient's body as foreign and attack the recipient's own cells.

Currently, HSCT patients receive prophylactic therapy before and after transplant to prepare their bodies for the procedure and to help manage their subsequent immune response. While this series of drugs is designed to help reduce patients' risk of developing GVHD, it also compromises their immune systems, leaving them vulnerable to serious infections and complications. Recent research has sought to determine ways to improve patients' initial immune response to transplanted cells as well as promote faster immune recovery after transplant.

Recent early-stage studies have demonstrated that a class of anti-cancer drugs known as histone deacetylase inhibitors (HDACi) may safely reduce the risk of GVHD in patients. These drugs have demonstrated an ability to "turn off" an enzyme that leads to inflammation, a major contributor to GVHD that develops as a byproduct of patients' intense immune response to HSCT. Based on those early results, researchers initiated the current study to evaluate whether one drug in this class, vorinostat, might reduce the risk of acute GVHD when added to current regimens.

To test this hypothesis, researchers enrolled 45 patients undergoing matched related donor HSCT from transplant centers at the University of Michigan in Ann Arbor, Mich. and Washington University in St. Louis to compare results of a standard regimen with vorinostat to historical controls. The primary endpoint of the single-arm, Phase I/II trial was the cumulative incidence of grade 2-4 acute GHVD (grade 1 is mildest; grade 4 is most severe). They aimed for an incidence of no more than 25 percent, compared with historical average rates of 42 percent.

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