Welcome!

News Feed Item

Advances in Stem Cell Research Techniques and New Transplant Strategies Reveal Opportunities for Improved Patient Outcomes with Reduced Risk of Complications

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.

Patients participating in the study received oral vorinostat daily in addition to standard preventive treatments prior to, during, and for 100 days after transplantation. After treatment, these patients had a significantly lower incidence of GVHD than their historical controls (22 % vs. 42%) and had lower rates of severe (grade 3-4) GVHD (4% vs. 19% in controls) and transplant-related mortality at one year (13% vs. 19% in controls). There were no differences in rates of infectious complications or incidence of relapse, indicating that vorinostat helped reduce the risk of GVHD in patients without further compromising their immune systems.

"While GVHD remains a challenging complication that affects a large proportion of patients who receive stem cell transplants, we are encouraged by the significant reduction in both the incidence and severity of this life-threatening condition that we observed in this trial," said Pavan Reddy, MD, senior author and Co-Director of the University of Michigan Bone Marrow Transplant and Hematologic Malignancies Program. "In order to increase the use of transplants and make them safer for more patients who need them, we need to see if this treatment approach may be successful in patients who receive stem cells from unrelated donors, and whether it may work among patients who are at high risk for severe GVHD. Moreover, we would like to confirm our findings in a larger, Phase III clinical trial."

Sung W. Choi, MD, lead author, will present this study in an oral presentation on Monday, December 10, at 4:45 p.m. EST at the Georgia World Congress Center in Room C108-C109, Level 1, Building C.

No Survival Advantage after Double Umbilical Cord Blood (UCB) Compared to Single UCB Transplant in Children with Hematological Malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) Randomized Trial [Abstract 359]

A study evaluating the efficacy of hematopoietic stem cell (HSC) transplants using single versus double units of transfused umbilical cord blood (UCB) for children with hematologic malignancies finds that the single unit approach remains the gold standard, refuting the notion that "more is better" in this clinical setting.

UCB contains a high concentration of HSCs with a unique immune profile that permits a high degree of human leukocyte antigen (HLA, proteins on white blood cells that determine compatibility between donor and recipient) mismatch, making it an increasingly popular source of HSCs for transplants. Questions remain, however, regarding the optimal quantity of transplanted umbilical cord stem cells. Previous research has found that double UCB transplant (the co-infusion of two partially HLA-matched units) is effective, particularly for adults for whom a single UCB unit is inadequate. Since prior research has connected cell quantity with survival, researchers hypothesized that a double UCB transplant may be superior to the use of a single unit in children with blood cancer for whom two units were available.

For this study, a team of researchers within the Blood and Marrow Transplant Clinical Trials Network examined whether the use of two units of UCB would offer a significant advantage in overall survival and other transplant outcomes such as blood and marrow recovery time, risks of acute and chronic graft-versus-host disease (GVHD), and transplant-related mortality and relapse.

As part of the multi-center, Phase III trial, 224 pediatric acute leukemia patients were randomized to receive either a single- or double-unit UCB transplant. After a median of 25 months of follow-up, nearly all patients (92%) in both study arms were in remission, with similar overall survival rates at one year post transplant between the groups (71% vs. 66% for the single vs. double unit, respectively). Overall, outcomes were similar between the groups, including disease-free survival (68% vs. 64% in single vs. double) and rates of relapse (12% vs. 14%), suggesting the double UCB transplant did not offer additional therapeutic benefit. While both study arms had the same overall rate of GVHD (57% each), patients who received a double UCB transplant experienced a higher risk of severe (grade 3-4) GVHD (23% vs. 14% for single unit patients), possibly attributed to the greater number of transplanted HSC.

"Our findings, though unexpected, affirm that the standard transplant approach of a single umbilical cord blood unit is optimal so long as the unit offers a sufficient number of cells. The study also demonstrated that a double umbilical cord blood transplant, while not better than a single cord blood transplant, can be an effective strategy among mainly adult patients for whom a single unit of cells is insufficient," said John Wagner, MD, lead author and Director of the Pediatric Blood and Marrow Transplant Program at the University of Minnesota in Minneapolis. "With this in mind, we need to focus our efforts on the development of new strategies that will enhance the speed of engraftment and immune recovery – and the double umbilical cord blood model may be a useful tool for achieving that goal."

Dr. Wagner will present this study in an oral presentation on Monday, December 10, at 8:00 a.m. EST at the Georgia World Congress Center in Room B312-313a, Level 3, Building B.

Prolonged Strenuous Exercise Expands the Population of Developmentally Early Stem Cells in Bone Marrow (BM) and Mobilizes them into Peripheral Blood – Novel Evidence that Strongly Supports a Positive Effect of Physical Activity on Extension of Life Span at the Level of Stem Cells [Abstract 584]

Researchers have demonstrated through a mouse model study that the beneficial effect of exercise on lifespan may be specifically related to the increase of a certain type of primitive stem cell believed to play an important role in tissue and organ regeneration.

Established research cites the benefit of exercise in reducing the risk of disease and managing chronic conditions, and studies have already shown that physical activity helps to mobilize stem cells, or move them from the bone marrow into the bloodstream. Taking this one step further, researchers focused their study on investigating the activity of the primitive stem cells (known as very small embryonic-like stem cells or VSELs) to directly assess whether strenuous exercise could increase the presence of a pool of developmentally early and highly potent stem cells in the blood stream. They hypothesized that the increased presence of these stem cells in the blood stream may enhance the rejuvenation of organs and tissues and potentially extend the lifespan.

To test their hypothesis, the team exposed the mice to various periods of strenuous exercise on rotating wheels (short-term at 1 day, mid-term at 14 days, and long-term at 6 months). The length of exercise was positively correlated to the counts of these primitive cells in their bone marrow and circulating blood, with the greatest increase in overall counts being in the group with the longest exercise exposure. The team also found similar correlations between the rates of exercise and the active function of genes that assist in organ and tissue regeneration. The data show that prolonged, strenuous exercise in mice is associated with the increased quantity of these important primitive stem cells in the bone marrow and their movement into the bloodstream.

"These data makes a compelling argument that exercise may not only prevent health issues that tend to emerge as people age, but may also help improve the body's ability to heal damaged tissue and organs," said Mariusz Ratajczak, MD, PhD, senior author and Director of the Stem Cell Institute at the James Graham Brown Cancer Center of the University of Louisville in Kentucky. "Additional studies need to be conducted to better define the role of these early stem cells in healing tissue damage, extending the lifespan, and maintaining health during the aging process, as well as to understand how we might be able to harness them for further therapeutic benefit."

Maciej Tarnowski, PhD, lead author, will present this study in an oral presentation on Monday, December 10, at 3:00 p.m. EST at the Georgia World Congress Center in Room C101, Level 1, Building C.

American Society of Hematology 54th Annual Meeting
The study authors and moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on new targeted treatment for chronic lymphocytic leukemia (CLL) and hard-to-treat blood disorders, efforts to reduce toxicity and improve survival for blood cancer therapy, and strategies to increase the efficacy and safety of treatments for clotting disorders. For the complete annual meeting program and abstracts, visit www.hematology.org/2012abstracts. Follow ASH (@ASH_hematology) on Twitter (use the hashtag #ASH12 when posting tweets about the meeting) and on Facebook at www.facebook.com/AmericanSocietyofHematology for the most up-to-date information about the 2012 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 50 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.

SOURCE American Society of Hematology

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
"Codigm is based on the cloud and we are here to explore marketing opportunities in America. Our mission is to make an ecosystem of the SW environment that anyone can understand, learn, teach, and develop the SW on the cloud," explained Sung Tae Ryu, CEO of Codigm, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
"With Digital Experience Monitoring what used to be a simple visit to a web page has exploded into app on phones, data from social media feeds, competitive benchmarking - these are all components that are only available because of some type of digital asset," explained Leo Vasiliou, Director of Web Performance Engineering at Catchpoint Systems, in this SYS-CON.tv interview at DevOps Summit at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
The “Digital Era” is forcing us to engage with new methods to build, operate and maintain applications. This transformation also implies an evolution to more and more intelligent applications to better engage with the customers, while creating significant market differentiators. In both cases, the cloud has become a key enabler to embrace this digital revolution. So, moving to the cloud is no longer the question; the new questions are HOW and WHEN. To make this equation even more complex, most ...
Enterprise architects are increasingly adopting multi-cloud strategies as they seek to utilize existing data center assets, leverage the advantages of cloud computing and avoid cloud vendor lock-in. This requires a globally aware traffic management strategy that can monitor infrastructure health across data centers and end-user experience globally, while responding to control changes and system specification at the speed of today’s DevOps teams. In his session at 20th Cloud Expo, Josh Gray, Chie...
Learn how to solve the problem of keeping files in sync between multiple Docker containers. In his session at 16th Cloud Expo, Aaron Brongersma, Senior Infrastructure Engineer at Modulus, discussed using rsync, GlusterFS, EBS and Bit Torrent Sync. He broke down the tools that are needed to help create a seamless user experience. In the end, can we have an environment where we can easily move Docker containers, servers, and volumes without impacting our applications? He shared his results so yo...
Businesses and business units of all sizes can benefit from cloud computing, but many don't want the cost, performance and security concerns of public cloud nor the complexity of building their own private clouds. Today, some cloud vendors are using artificial intelligence (AI) to simplify cloud deployment and management. In his session at 20th Cloud Expo, Ajay Gulati, Co-founder and CEO of ZeroStack, discussed how AI can simplify cloud operations. He covered the following topics: why cloud mana...
FinTechs use the cloud to operate at the speed and scale of digital financial activity, but are often hindered by the complexity of managing security and compliance in the cloud. In his session at 20th Cloud Expo, Sesh Murthy, co-founder and CTO of Cloud Raxak, showed how proactive and automated cloud security enables FinTechs to leverage the cloud to achieve their business goals. Through business-driven cloud security, FinTechs can speed time-to-market, diminish risk and costs, maintain continu...
Creating replica copies to tolerate a certain number of failures is easy, but very expensive at cloud-scale. Conventional RAID has lower overhead, but it is limited in the number of failures it can tolerate. And the management is like herding cats (overseeing capacity, rebuilds, migrations, and degraded performance). In his general session at 18th Cloud Expo, Scott Cleland, Senior Director of Product Marketing for the HGST Cloud Infrastructure Business Unit, discussed how a new approach is neces...
"This week we're really focusing on scalability, asset preservation and how do you back up to the cloud and in the cloud with object storage, which is really a new way of attacking dealing with your file, your blocked data, where you put it and how you access it," stated Jeff Greenwald, Senior Director of Market Development at HGST, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Docker containers have brought great opportunities to shorten the deployment process through continuous integration and the delivery of applications and microservices. This applies equally to enterprise data centers as well as the cloud. In his session at 20th Cloud Expo, Jari Kolehmainen, founder and CTO of Kontena, discussed solutions and benefits of a deeply integrated deployment pipeline using technologies such as container management platforms, Docker containers, and the drone.io Cl tool. H...
Everything run by electricity will eventually be connected to the Internet. Get ahead of the Internet of Things revolution. In his session at @ThingsExpo, Akvelon expert and IoT industry leader Sergey Grebnov provided an educational dive into the world of managing your home, workplace and all the devices they contain with the power of machine-based AI and intelligent Bot services for a completely streamlined experience.
Kubernetes is a new and revolutionary open-sourced system for managing containers across multiple hosts in a cluster. Ansible is a simple IT automation tool for just about any requirement for reproducible environments. In his session at @DevOpsSummit at 18th Cloud Expo, Patrick Galbraith, a principal engineer at HPE, discussed how to build a fully functional Kubernetes cluster on a number of virtual machines or bare-metal hosts. Also included will be a brief demonstration of running a Galera MyS...
It is of utmost importance for the future success of WebRTC to ensure that interoperability is operational between web browsers and any WebRTC-compliant client. To be guaranteed as operational and effective, interoperability must be tested extensively by establishing WebRTC data and media connections between different web browsers running on different devices and operating systems. In his session at WebRTC Summit at @ThingsExpo, Dr. Alex Gouaillard, CEO and Founder of CoSMo Software, presented ...
Enterprises are universally struggling to understand where the new tools and methodologies of DevOps fit into their organizations, and are universally making the same mistakes. These mistakes are not unavoidable, and in fact, avoiding them gifts an organization with sustained competitive advantage, just like it did for Japanese Manufacturing Post WWII.
DXWorldEXPO LLC, the producer of the world's most influential technology conferences and trade shows has announced the 22nd International CloudEXPO | DXWorldEXPO "Early Bird Registration" is now open. Register for Full Conference "Gold Pass" ▸ Here (Expo Hall ▸ Here)