A new treatment using leukemia patients' own infection-fighting cells appears to protect them from infections and cancer recurrence following treatment with fludarabine-based chemotherapy, according to new research from the Perelman School of Medicine at the University of Pennsylvania.
The new process is a step toward eliminating the harsh side effects that result from the commonly prescribed drug, which improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) but destroys patients' healthy immune cells in the process, leaving them vulnerable to serious viral and bacterial infections. The drug's effects on the immune system tend to be so violent that it has been dubbed "AIDS in a bottle."
Today at the 53rd American Society of Hematology Annual Meeting, the research team will present results showing how they use a patient's own T cells to repair his or her immune system after fludarabine treatment. With a restored immune system, patients can stop taking prophylactic antibiotics and may have prolonged progression-free survival.
"Fludarabine is a double-edged sword," says Stephen J. Schuster, MD, an associate professor in the division of Hematology-Oncology and director of the Lymphoma Program at Penn's Abramson Cancer Center. "Although it is very active at killing CLL cells, it is also very active at killing normal cells in the immune system, particularly T lymphocytes, which are the master regulators of the immune system. So you rid the patient of their disease, but you also rid them of a normal immune system."
Thirty-four patients enrolled in the multicenter study. Prior to chemotherapy treatment, the researchers isolated healthy T lymphocytes from each patient's blood. When the patient finished chemotherapy, the team grew the T cells in Penn's Clinical Cell and Vaccine Production Facility using a technique that induces them to proliferate rapidly. The researchers then infused the expanded T cells back into the patient. "What we showed was that by giving them back their own T cells after treatment, we can restore patients' immune systems," Schuster said.
"Within four weeks of the T cell infusion, their T cell counts were within the normal range."
After chemotherapy and prior to T cell infusion, the median CD4 T cell count for fludarabine-treated patients was 119 cells/ml blood and the median CD8 T cell count was 80 cells/ml. Thirty days after the patients received the infusion of their own T cells, the median cell counts were in the normal range, at 373 cells/ml and 208 cells/ml for CD4 and CD8 cells, respectively. The T cell numbers remained in the normal range beyond 90 days, leading Schuster and colleagues to conclude that the autologous T cell transfer repaired the immune system of patients.
Although all of the patients' T cell counts returned to the normal range after treatment, not all patients responded equally well to the T cell therapy. Patients who had a complete response to chemotherapy had a more robust T cell recovery than did patients who had only a partial response. "We believe that having a complete remission of CLL seems to create a larger space for the normal immune cells to expand into," Schuster says. "Somehow, the cancer seems to interfere with recovery of the immune system."
In addition to quashing the complications ordinarily associated with treatment, the team hopes that the restored immune system will help keep the cancer in check. At a median follow-up of 14 months after T cell infusion, two-thirds of the patients remain progression-free. Longer follow up will be needed to compare treatment results for patients receiving T cells with published results for patients receiving similar chemotherapy without T cell support.
What is clear from the small trial is that patients can safely stop prophylactic antibiotic therapy after their T cell numbers rebound. Physicians regularly keep CLL patients on extended prophylactic antibiotic therapy to help stave off infections. In this study, though, patients stopped taking antibiotics about a month after receiving T cells without developing significant infections.
In addition to the Penn researchers, investigators from the MD Anderson Cancer Center, the Baylor College of Medicine, Texas Children's Hospital, and the Methodist Hospital in Houston also participated in the study.
The study was funded by the CLL Global Research Foundation.
This research will be presented Sunday, December 11, 2011 between 6 PM and 8 PM 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!
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy
29.05.2017 | Statistics