Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn study points to novel way to improve outcomes from umbilical cord blood transplants

12.12.2011
Technique expands scarce resources used for cord blood transplant procedure

A new method to boost the number of immune cells in umbilical cord blood prior to cord blood transplants for cancer patients appears to lead to a quicker rebuilding of a new immune system in the patient's body than with a conventional cord blood transplant procedure, according to new research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today at the 53rd American Society of Hematology Annual Meeting. The technique also paves the way for the development of a way to provide these transplant patients with a salvage therapy from the same donor if their cancer returns.

"Umbilical cord blood is a potential cancer therapy that is thrown away every day," said lead author Elizabeth Hexner, MD, an assistant professor in the division of Hematology-Oncology in Penn's Abramson Cancer Center. "Our findings point to a promising method to make better use of scarce cord blood resources available through public banks, which offer the only transplant option for patients who have no suitably matched blood or bone marrow donor prospects."

Though cord blood has a larger number of stem cells by volume than blood or marrow from living donors, the actual amount of blood available per cord is smaller – containing about one tenth the number of cells collected from living donors. That deficit typically leads to a slower rebuilding of a sick patient's new immune system following transplant, leaving patients vulnerable to severe, even life-threatening infections. On the other hand, because immune cells in cord blood are less developed and have not been fully "educated" to attack perceived invaders in the body, patients who undergo cord blood transplants are less likely to suffer graft-versus-host disease (GVHD) -- a common, dangerous complication in which the new cells assault healthy organs like the liver and skin -- doctors say that improvements to the transplant procedure hold great potential.

The procedure used in the Penn trial, involving four patients, began with cord blood donations that had been separated into two parts – typically an 80 percent fraction and a 20 percent fraction – prior to freezing. Then, the team thawed the smaller fraction two weeks prior to transplant, activated and grew the number of donated T cells -- which are a key driver for the process that recovers transplant patients' immune system and play a role in fighting infections -- using the co-stimulatory compounds CD3 and CD28 in Penn's Clinical Cell and Vaccine Production Facility. Following a chemotherapy and radiation regimen to destroy patients' remaining cancer cells and the administration of immunosuppression drugs to prevent rejection of the donor cells, patients then received the thawed, larger fraction of the cord blood first (a standard, single cord blood transplant). An infusion of the newly activated and expanded T cells followed, with a portion of those cells being reserved and frozen for potential future use as immunotherapy in the event of a cancer relapse or transplant failure.

"Donor lymphocyte infusions (DLI) are frequently given to patients who need them following stem cell transplants from living donors, but until now, we have been unable to offer this therapy to cord blood transplant patients because the source of their cells is used up at the time of transplant," Hexner says. "Our results show that we are able to grow sufficient numbers of T cells to be available both for that use as well as to buoy the number of cells that patients receive during the transplant itself, which seems to have helped their immune systems come back online more quickly than is typically seen in umbilical cord blood transplants."

Three of the patients enrolled on the study experienced relatively early neutrophil engraftment – the point at which these critical infection fighting cells in our body reach 500 per microliter. This milestone is important because above this threshold, the risk of life-threatening infections is drastically lower. For these three patients, engraftment was achieved on days 12, 20, and 17 post-transplant. This was approximately half the time this process has historically taken with this type of transplant, substantially narrowing the window in which patients have the greatest risk of death from transplant complications. Research has shown that using two cords per transplant can also speed this process, but that tactic also doubles the cost of the procedure, to more than $60,000. The fourth trial patient's umbilical cord blood graft failed, and they were subsequently treated with another stem cell transplant. There were no infusion-related adverse events observed during the trial, and three of the four expansion samples yielded enough cells for future immunotherapeutic DLI use. Next, the team hopes to test the optimal expanded T cell dose necessary for speeding the process of immune recovery and develop a method to perform DLI after transplant.

Though the new research paves the way for improvements in the use of existing cord blood resources to improve transplant outcomes, the Penn team says their work also sheds light on the need to buoy the number of public cord blood banks through which new parents can opt to donate their newborns' cord blood for use treating sick patients. Commercial, private cord blood banks have proliferated in the United States in recent years, despite a lack of evidence proving the utility of this so-called "biological insurance" and statements from the American Academy of Pediatrics and other groups discouraging new parents from paying for the service.

Since cord blood stored in public banks is already frozen and awaiting use, it offers a less labor intensive, quicker way to match patients for transplant than the two to three month timeframe for locating and obtaining cells from a matching unrelated donor through the National Marrow Donor Program. Blood stored in private banks, however, is not available for treatment of unrelated donors for whom a living blood or marrow donor cannot be located.

"In many parts of the country, even families who want to donate their infant's cord blood for care of unrelated sick patients are not able to do so because no public bank exists in their area," Hexner says. "Greater investment in public banks and more opportunities for parents to donate to these banks are a necessary component of improving care for patients with blood cancers."

The trial was funded by the Leukemia and Lymphoma Society, the National Institutes of Health (K23 NHLBI K23-HL-093366), and from the Abramson Cancer Center's Alan Steinberg Scholars in Cancer Research Fund.

The study will be presented from 6 PM to 8 PM PST in Hall GH of the San Diego Convention Center.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Holly Auer | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>