All fifty-eight patients, with a median age of 63 and all with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome – a pre-leukemic condition – saw their blood cancers go into remission using a novel combination of low-intensity chemotherapy, targeted radiation delivery by an antibody and a stem-cell transplant.
Forty percent of the patients were alive a year after treatment and approximately 35 percent had survived three years, about the same rates as patients who received similar treatment but whose disease was already in remission and who had much more favorable risk for relapse when therapy began.
Results of the research appear online in the journal Blood. The principal investigator and corresponding author of the paper is John Pagel, M.D., Ph.D, a transplant oncologist and assistant member of the Hutchinson Center's Clinical Research Division.
The purpose of the study was to find the maximum dose of radiation that patients could tolerate with acceptable toxic side effects, not to assess how effective the novel treatment was, according to Pagel and colleagues. However, "the results appear to be very encouraging and warrant us to study it further for patients who really have no significant other curative options," Pagel said.
Older (over age 50) patients with active, advanced leukemia and myelodysplastic syndrome pose the most difficult treatment challenges because standard transplant therapy rarely works, according to Pagel. Both standard and low-dose therapies (a process sometimes known as a "mini transplant" and pioneered at the Hutchinson Center) used to kill leukemia cells in the bloodstream in preparation for a transplant usually require that patients be in remission.
The patients in this study, who came from all over the world to participate in the Phase 1 clinical trial, were in large part those with active relapsed disease that in many cases had failed to respond to standard therapies. Eighty-six percent of the 58 patients had active disease and only 10 percent were in remission when therapy was begun. Their cancers had failed previous treatment attempts. "These were people who had extremely advanced high-risk disease, they were typically older – most of them were in their 60s and some were in their 70s – and had few or no other options for a potential cure. In fact most, if not all, would not been offered a stem cell transplant here or elsewhere. It is fair to say that these patients would likely have died without a transplant being performed if they had not been given the opportunity to participate in this study."
To find the optimal dose of radiation, researchers began at 12 Gy (Gray, a unit of measurement of absorbed radiation dose) and escalated the dosages in increments of 2 Gy up to a Gy of 26. At that dose, some toxicity to the heart and lungs was found so they concluded 24 Gy to be the maximum effective dosage. The 21 patients who received the maximum radiation dose have survived the longest, researchers reported.
The key to success in this study was use of a radiolabeled antibody that has therapeutic iodine 131 attached and is designed to target leukemic bloods cells that carry a marker on the surface of the cell known as CD45. Its use in delivering targeted amounts of radiation was developed several years ago at the Hutchinson Center. Delivered intravenously, the radiation looks for the CD45 antigen receptor on the surface of blood cells. This approach results in a two- to four-fold increase in the amount of radiation that reaches cancerous cells as compared to standard external beam radiation, which also radiates normal surrounding organs and tissue. The more radiation that can be applied, the more cancer cells will be killed in preparation for donor stem cells to take over the diseased immune system and kill off the remaining cancer cells.
Pagel said further research is needed to test more patients at the highest radiation dose both at the Hutchinson Center and at other transplant centers around the country.
Joining Pagel in the study were colleagues from the Hutchinson Center, the Pacific Northwest Laboratory and the departments of Medicine, Pediatrics and Nuclear Medicine at the University of Washington School of Medicine.
Grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, the Damon Runyon Cancer Research Foundation, the Edson Foundation and the Frederick Kullman Memorial Fund supported this research.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.
Dean Forbes | EurekAlert!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy