Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New blood transplant method stops fatal side effect, Stanford study finds

30.09.2005


Marty Holmes, a landscaper from Stockton, Calif., had never heard of a regulatory T cell before his doctor suggested that it could be the key to helping him survive his cancer.



Holmes recalled that he didn’t bat an eye when the doctors proposed an experimental radiation and drug procedure to help boost these cells, even though it had been tested almost solely in mice. "As long as there was any percentage of hope, I just shot for that," he said of the decision he made last year. "I felt privileged to be a human guinea pig."

Findings published in the Sept. 29 issue of the New England Journal of Medicine suggest that the new therapy pioneered at Stanford University School of Medicine has paid off for Holmes and other lymphoma and leukemia patients. Holmes became the 40th person to undergo this procedure after Stanford researchers had shown that it could boost the relative levels of regulatory T cells in the immune system of mice - an effect that turned out to be beneficial before undergoing a hematopoietic (blood) stem cell transplantation, a common treatment for blood cancers.


Blood stem cell transplantation replaces the cancerous blood cells of a leukemia or lymphoma patient with those from a healthy donor. The transplantation cures the cancer, but in up to 80 percent of the cases there is a potentially deadly side effect: The donor’s incoming immune cells attack the patient’s body as "foreign" in what is known as graft-versus-host disease.

The new method tested at Stanford appears to retain the desired result of the transplantation - killing the cancerous cells - without inducing the acute form of graft-versus-host disease. "It allows you to throw out the one effect but not the other," said Samuel Strober, MD, professor of medicine (immunology and rheumatology) and the senior author of the study.

Among the 37 study participants included in the National Institutes of Health-funded clinical trial, there was more than a tenfold reduction in the incidence of acute graft-versus-host disease. Only 5 percent, or just two patients, experienced the acute form of the disease.

"You would have expected something in the order of 30 to 60 percent incidence of severe graft-versus-host disease in these patients, according to conventional methods," said Strober. "And it didn’t look like there was a price to be paid for this major reduction," he added, explaining that the patients did not have any higher rate of infections or relapse.

The majority of patients who were in partial remission went into complete remission, and those who were in complete remission didn’t relapse over the course of the three-year study.

The treatment was not as effective in stemming the less-serious, chronic form of graft-versus-host disease. The study found no apparent difference in the typical rates of the chronic form of the condition among the patients who survived more than 100 days after transplantation.

Acute graft-versus-host disease occurs within 100 days of transplantation and involves the donor immune cells attacking the host’s skin, intestines and liver. It is lethal in up to 40 percent of the cases. Chronic graft-versus-host disease is characterized by such long-term problems as dryness of the eyes and mouth, skin rashes, stiff joints, weight loss caused by intestinal scarring, and more infections due to a weakened immune system.

"We didn’t seem to impact much on the incidence of chronic graft-versus-host disease, maybe a bit," said the paper’s first author, Stanford assistant professor of medicine Robert Lowsky, MD. "With the acute form we did wonders, and acute is often the more worrisome complication."

Robertson Parkman, MD, an immunologist who was not involved in the study, said that the new procedure "is definitely a significant improvement" over the existing methods. He did, however, find it a bit problematic that the patients continue to show some chronic graft-versus-host disease. "Reducing acute graft-versus-host disease is a good thing, but this approach may not be as much of a total panacea as we’d like it to be," said Parkman, professor of pediatrics in the Division of Research Immunology/Bone Marrow Transplant at Children’s Hospital Los Angeles.

The Stanford researchers said that more research is needed, and they hope to begin testing their method with other cancer centers soon.

From Mice to Men

It makes sense that the regulatory T cells - a tiny subset of immune cells - could play such a vital role in stemming graft-versus-host disease: These cells appear to act as the immune system’s peacekeepers, signaling to other immune cells to hold off from attacking an intruder. Thus, it seemed promising to use them to stop the newly transplanted cells from attacking the host.

Strober has studied regulatory T cells for more than 25 years. He weathered through a time when many immunologists doubted that regulatory (formerly called suppressor) T cells even existed. Through the years, he fine-tuned a method to harness the elusive cells’ immune system-soothing abilities in mice. Using a combination of irradiation and antibodies, he was able to preferentially boost the mice’s regulatory T cells from about 1 percent of the total T cells to more than 90 percent. The treated mice had a dramatic reduction in acute graft-versus-host disease compared with untreated mice following a blood stem cell transplantation.

But would the strategy be as successful in humans? To find out, he teamed up with Lowsky, who had experience trying novel strategies for improving blood stem cell transplantations as director of the blood and marrow transplantation program of the Saskatchewan Cancer Agency until moving to Stanford in 2001. Together, Lowsky and Strober modified the mouse protocol to be used in humans.

"The beauty of this study is that it is a practical example of translating an animal model to the clinic," said Lowsky.

The Marathon Man

Holmes is certainly glad that he could benefit from the trial. He had been referred to Stanford for a blood stem cell transplantation in July 2004. It had been six years since, at age 38, he had noticed a golf-ball-sized lump in his armpit and found out that he non-Hodgkin lymphoma. Doctors at Stanford identified him as a good candidate for the new transplantation procedure.

In Holmes’ case, the incoming cells - shipped from Germany - were from an unrelated donor who was not completely matched. Lowsky explained that without using the regulatory T cell-boosting procedure, Holmes would have been likely to experience a great deal of graft-versus-host disease because of the differences between Holmes’ cells and the donor’s that could have triggered immune responses.

Although Holmes has experienced some of the effects of chronic graft-versus-host disease - skin rashes and sores in his mouth - he has gone from a partial remission to complete remission. Indeed, Holmes said he noticed an immediate improvement following transplantation. "I was gaining weight and getting my energy level back," he said, "but I thought the only way to know for sure was to test myself, to force myself to do something really challenging."

A few months ago, Holmes, who refers to himself as "The Cancer Challenger," decided to do a marathon without any prior training just 10 days before the event and less than a year after his transplant. At a follow-up clinic visit after he had completed the race, Holmes said Lowsky was amazed to hear that he had undertaken such a challenge at that stage of his recovery. Lowsky immediately looked up the race results online. Sure enough, he found that Holmes had placed 15,354th.

"I won’t say it wasn’t painful," said Holmes, who finished the marathon in seven hours and 13 minutes, mostly walking, "but it doesn’t compare to some of the things I went through having cancer."

Mitzi Baker | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

nachricht X-ray experiments reveal two different types of water
27.06.2017 | Deutsches Elektronen-Synchrotron DESY

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Collapse of the European ice sheet caused chaos

27.06.2017 | Earth Sciences

NASA sees quick development of Hurricane Dora

27.06.2017 | Earth Sciences

New method to rapidly map the 'social networks' of proteins

27.06.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>