Stem Cell Transplantation Research At The Cancer Center At Hackensack University Medical Center Aims To Develop 'Designer' Transplants

Main Category: Stem Cell Research
Also Included In: Transplants / Organ Donations
Article Date: 24 Jul 2008 - 2:00 PST

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Over the past two decades, stem cell transplantation has evolved from being an experimental treatment to one that is a viable option for patients with hematologic (blood) malignancies and other life-threatening blood disorders. Researchers and clinicians at the Adult Blood and Marrow Stem Cell Transplantation Program at The Cancer Center at Hackensack University Medical Center are responsible for many of the innovations and techniques used in today's successful transplants.

Stem cell transplantation researchers in The Cancer Center's Division of Research recently published results of a study in Blood, the scientific journal of the American Society of Hematology, that may take physicians one step closer to performing customized "designer" stem cell transplants that could lead to better treatment outcomes for patients.

The paper, "Overlap Between in vitro Donor Anti-Host and in vivo Post Transplantation T Cell Response Vβ Utilization: A New Paradigm for Designer Allogeneic Blood and Marrow Transplantation," was co-authored by Cancer Center researchers Thea Friedman, Ph.D., director of laboratory research; Robert Korngold, Ph.D., chief of the Division of Research; Michele L. Donato, M.D., director of the Blood and Marrow Collection Facility; and Scott D. Rowley, M.D., chief of the Division of Blood and Marrow Stem Cell Transplantation; and researchers from the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia. The paper confirms that a technique - called Vβ (beta) spectratype analysis - can be used to identify mature donor T cells (disease-fighting white blood cells) that can be harmful to the patient.

One of the major risks of an allogeneic transplant (one that uses stem cells removed from a donor) is graft-versus-host disease (GVHD). GVHD is a potentially fatal complication that can occur when mature donor T cells that are transferred along with stem cells from donated blood or bone marrow (the graft) stage an immune response to the "foreign" antigens in the tissues of many organs of the host's (patient's) body. These anti-host donor T cells attack the tissues and can cause major organ failure or even death. Past research conducted by Dr. Friedman and Dr. Korngold showed that these GVHD-causing T cells can be removed from the graft to avoid development of disease, and the remaining T cells can mount responses against residual cancer cells like leukemia.

"Following allogeneic blood and marrow transplantation, mature donor T cells can enhance the engraftment process to grow new stem cells, can counteract opportunistic infections, and mount a fight against the cancerous cells but at the risk of developing GVHD," says Dr. Friedman. "The challenge for researchers is to find a way to enhance the ability of these T cells to destroy residual cancerous cells while avoiding or controlling the T cells' GVHD response."

Dr. Friedman continues: "Our Vβ spectratype analysis is a powerful tool for identifying which donor T cell families cause trouble and which are helpful. With this current research, we investigated the potential of using this spectratype approach to compare donor anti-host T cell responses generated in culture with those detected in the patient after transplantation. Our results showed that there was a robust overlap between the in vitro culture responses and those in the patient, indicating that what was seen in vitro was representative of what would happen in the patients."

The researchers went a step further to evaluate whether the theoretical manipulation of a transplant by removing donor T cells that might launch a GVHD response could prove harmful by also risking the unnecessary loss of beneficial T cells.

"Our results indicated that overall there was a low risk of losing beneficial T cells," says Dr. Friedman. "This research will enable us to predict before the transplant what kind of a response we would get in a patient after the transplant. Ultimately, our goal is to be able to use this technique to guide us in customizing the transplantation process to obtain better treatment results for patients."

The research involved 18 patients, ranging in age from 30 to 69 years who were diagnosed with various hematological cancers and serious blood disorders. They were followed by the research team for several years.

This research is funded by grants from the NIH and the Amy Strelzer Manasevit Research Program of the National Marrow Donor Program.

"The studies in stem cell transplantation being conducted at The Cancer Center help to contribute to very favorable outcomes rates for our Adult Blood and Marrow Stem Cell Transplantation Program," says Andrew L. Pecora, M.D., chairman and executive administrative director.

Each year between 80 and 100 patients undergo allogeneic stem cell transplantation at The Cancer Center at Hackensack University Medical Center. With the addition of autologous stem transplants, the program's experts perform more than 350 stem cell transplants every year, making it one of the 10 largest in the United States.

The Cancer Center is New Jersey's largest and the one ranked the best cancer center in the state by New York magazine.

The Cancer Center
http://www.humc.com