Although bone marrow transplants have long been standard for acute leukemia, current treatments still rely on exact matches between donor and patient.
Now, scientists at the University of Perugia, Italy, and the Weizmann Institute of Science have improved on a method of transplanting bone marrow-based stem cells from a mismatched donor, making it safer for use when no exact match exists. They were invited to present their findings at the recent annual American Society of Hematology conference in New Orleans.
More than a decade ago, Prof. Yair Reisner of the Weizmann Institute's Immunology Department pioneered a method for transplanting stem cells from family members who are a partial match. Based on these studies (in mice), he joined forces with Prof. Massimo F. Martelli, Head of the Hematology and Clinical Immunology Section at the University of Perugia, to demonstrate in more than 300 patients that the cure rate of these so-called "mega dose" transplants is similar to that of transplants from matched, unrelated donors picked from international bone marrow donor registries. To combat the body's tendency to reject the foreign cells, these stem cells are stripped of immune cells called T cells and given in high doses that overwhelm the host's own immune system.
Although removing donor T cells from the bone marrow reduces the risk of graft-versus-host disease - caused when the T cells attack the recipient's tissues - the immune system is slow to recover after the transplant, leaving the patient at risk of serious infection. Doctors are faced with a difficult choice: Either remove the T cells from the bone marrow, increasing the risk of infection, or leave the T cells in the graft, putting the patient at risk for lethal graft-versus-host disease.
Martelli, working with Reisner, has now found a way to facilitate the recovery of the immune responses in recipients of T cell-depleted bone marrow transplants. In a clinical trial, 25 of 26 leukemia and lymphoma patients who received mismatched mega dose T cell-depleted stem cell transplants from relatives showed prompt immune recovery, and their immune systems were functioning well several months later.
The scientists knew that certain regulatory T cells (T regs), rather than causing graft-versus-host disease, could actually help to prevent it in mice. T regs have also been shown to keep other immune responses in check, including preventing autoimmune attacks on the body's own cells. In the present study, after purifying T regs from the donor's blood, the cells were infused intravenously into the cancer patients, who had previously undergone standard radiation and chemotherapy treatments. Three days later, the patients received the donor stem cells, along with another kind of T cell - those that fight disease.
The patients who underwent this procedure showed quick, lasting improvements in immune activity; most experienced no symptoms even though they received large doses of the T cells that are generally associated with lethal graft-versus-host disease.
Further follow up on these patients and additional clinical trials will be needed before the procedure can be widely adopted. But these results strongly suggest that T regs used in mega-dose stem cells will further enhance the cure rate for bone marrow transplant patients without a matched donor in the family.Prof. Yair Reisner's research is supported by the M.D. Moross Institute for Cancer Research; the Kirk Center for Childhood Cancer and Immunological Disorders; the Mario Negri Institute for Pharmacological Research Weizmann Institute of Science Exchange Program; the Gabrielle Rich Center for Transplantation Biology Research; the Russell Berrie Foundation; and Mr. and Mrs. Seymour Spira, Palm Beach Gardens, FL.
Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair in Immunology.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Weizmann Institute news releases are posted on the World Wide Web at http://wis-wander.weizmann.ac.il, and are also available at http://www.eurekalert.org.
Yivsam Azgad | idw
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
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...
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...
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...
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...
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)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology