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Stem Cell Therapy: What Physicians Should Know
Tremendous progress has been made in the field of hematopoietic stem cell transplants (SCT). Once considered a last resort for leukemia patients after chemotherapy failed or a cancer relapsed, SCT is now prescribed earlier in the treatment regiment for leukemia, lymphoma, myelomas, nonmalignant blood disorders such as sickle cell anemia, and metabolic disorders.
Improvements in the safety and refinement of SCT have also resulted in an increase in the age of candidates. Now a patient in their mid 70s with blood cancer can be considered for both autologous and allogeneic (related and unrelated donor) transplants with a good likelihood of having a beneficial response. In fact, the prognosis for SCT patients of all age levels — pediatric and adult — has significantly improved due to new pre-transplant protocols that reduce toxicity from chemotherapy and radiation, and even newer post-transplant treatments, for example, to reduce graft-versus-host disease (GVHD) and other side effects.
And there’s more, much more, according to Stanton Gerson, MD, director of UH Seidman Cancer Center and the Case Comprehensive Cancer Center, and Marcos JG de Lima, MD, director of UH Seidman’s Hematologic Malignancies and Stem Cell Transplant Program which focuses on non-embryonic stem cells.
Dr. Gerson serves on the National Cancer Institutes Board of Scientific Advisors which helps guide the nation’s effort in cancer discovery and research. He recently recruited Dr. de Lima from the University of Texas MD Anderson Cancer Center in Houston, where Dr. de Lima served as professor of medicine in the Department of Stem Cell Transplantation and Cellular Therapy, and director of the Unrelated Donor Program. A past president of the National Marrow Donor Program Council and advisor for the Center for International Bone Marrow Transplant Research, Dr. de Lima is currently protocol design co-chair of the National Cancer Institute-Sponsored International Workshop on Relapse after Allogeneic Hematopoietic Stem Cell Transplantation and treasurer of the American Society of Blood and Marrow Transplantation.
“UH has been at the forefront of SCT since its researchers helped pinpoint stem cells as the therapeutic component of bone marrow more than 30 years ago,” says Dr. Gerson, who has championed a number of innovative therapies and activities. “Today, our physicians and scientists are active not only in local investigator-initiated studies, but also in many large national cooperative group studies and clinical trials, including the elite Bone Marrow Transplant Clinical Trials Network, the Eastern Cooperative Oncology Group, the Bone Marrow Transplant Information Network and the Pediatric Blood and Marrow Transplant Information Network.”
A recent study involves the use of mesenchymal stem cells and multi-potent adult progenitor cells, which are similar to mesenchymal stem cells but possess greater proliferative and regenerative properties. In collaboration with a local biotechnology cell therapy company called Athersys, UH Seidman Cancer Center researchers are currently investigating the role of these cells in GVHD and their use in allogeneic transplantation.
UH Seidman Cancer Center also has an active umbilical cord blood transplant program as an alternative stem cell source for patients — adult as well as pediatric — who do not have a related matched donor. Umbilical cord blood transplant is limited by the relatively small stem cell content, according to Dr. de Lima who plans to investigate ex vivo expansion of cord blood cells in the lab prior to transplanting them into the patient, in order to induce faster engraftment.
“It’s an issue of improving access to treatment,” says Dr. de Lima. “Cord or placenta blood increases the possibility of offering transplants to more people, because these cells are immunologically naïve — leading to less stringent matching criteria and an increased donor pool for minorities (which are under-represented in the national registry).”
One of the biggest issues in leukemia management is which patients actually need to have transplantation and, of those, how to make it safer because of GVHD. So researchers at UH Seidman Cancer Center are looking at a certain type of lymphocytes called KIR (killer immunoglobulin receptor) cells and categorizing the KIR status of the donor visa vi the recipient to identify the safer transplant donor for the patient. The expectation is that GVHD will be significantly reduced. Dr. de Lima is also interested in epigenetic manipulation of the immune-mediated graft-versus-leukemia and graft-versus-host disease phenomena.
Patients with myelodysplastic syndrome and with chronic lymphocytic leukemia are two populations with very difficult to treat disorders for which transplantation has not historically been used very frequently. At UH Seidman Cancer Center these patients, especially those who are characterized as being at high risk because of chromosomal mutations in their bone marrow status, are being actively evaluated for allogeneic transplantation.
“The results are so good,” Dr. Gerson reports. “We’re finding that a significant number of these patients can have the disease either cured or corrected by transplantation.”
Clinical trials investigating preparative regimens and post-transplant supportive therapies have also resulted in new protocols for acute lymphocytic leukemia patients to improve safety and outcomes. Along those same lines, UH Seidman Cancer Center is studying vaccines, antibodies and an immunogen named B212 and their ability to reduce toxicity and improve outcomes in patients with advanced lymphomas.
“We have and are developing clinical trials that are actually redefining, and sometimes defining, standards of care,” says Dr. de Lima, who plans to work with his UH Seidman Cancer Center colleagues to develop and offer patients access to clinical studies covering most hematologic malignancies. “We are working very hard to find new treatments that could, hopefully with time, lead us to an increased cure rate.”
For more information about UH Seidman Cancer Center’s Hematologic Malignancies and Stem Cell Transplant Program, visit UHSeidman.org. To refer a patient, call (216) 844-3951.