Cord blood transplantation has grown from just five transplants in 2005 to 44 in 2009 in both pediatric and adult patients at Seattle Cancer Care Alliance. This issue focuses on this burgeoning stem cell resource and the exciting life-saving clinical trials being conducted here.
- Using Expanded Cord Blood Units for Transplantation. A Fred Hutchinson Cancer Research Center clinical research division study details the first successful use of expanded umbilical cord blood units and the potential for increased donor matches.
- Active Clinical Trials for Pediatric BMT. There are nearly 80 hematology/oncology trials at Seattle Cancer Care Alliance. The five listed here are related to cord blood transplantation research.
- Best Transplant Outcomes in the U.S. The Fred Hutchinson Transplant Program at SCCA was ranked first in outcomes in a four-year study by the National Marrow Donor Program (NMDP) that measured one-year survival rates of patients among 122 transplant centers in the United States.
- Most Experience Transplant Doctors in the World. The Hutchinson Center has performed more transplants than any other transplant center in the world. And patients who choose to have their transplants at centers that perform a high number of such procedures generally have better outcomes.
- Colleen Delaney, MD. Dr. Colleen Delaney and her team have discovered a way to manipulate stem/progenitor cells in the lab with the goal of increasing their numbers. As Director of the Program in Cord Blood Transplantation and Research, Delaney has real-life uses for her medical breakthroughs.
(From Center News Weekly January 18, 2010)
Hutchinson Center scientists have cleared a major technical hurdle to making umbilical cord blood transplants a more widely used method for treating leukemia and other blood cancers.
In a study published in the Jan. 17 edition of Nature Medicine, Dr. Colleen Delaney, director of the Cord Blood Transplant Program at Hutchinson Center, and colleagues describe the first use of a method to vastly expand the number of stem/progenitor cells from a unit of cord blood in the laboratory. When the cells were infused into patients, successful and rapid engraftment resulted.
The relatively small number of stem cells in cord blood units (about 10 percent of what a patient receives from a conventional transplant) has been a reason that cord blood transplants take much longer to engraft than standard stem cell transplants from donors. The longer the engraftment takes, the higher the risk of immuno-compromised patients acquiring life-threatening infections because they have essentially no white blood cells to fight them.
Despite the numbers disadvantage, cord blood is a promising source of stem cells to replace diseased blood and immune systems through stem cell transplantation because the donated cells don’t need to be perfectly matched to the patient. About 30 percent of patients overall who need a stem cell transplant can’t find a suitable donor. About 95 percent of racial-minority patients cannot find a match.
The use of expanded cord blood units could decrease the risk of early death, which is higher in patients receiving a cord blood transplant without an expanded cell count. Further clinical trials and technological improvements are needed to verify the efficacy of cord blood transplants that use expanded units, the authors said.
“The real ground-breaking aspect of this research is that we have shown that you can manipulate stem/progenitor cells in the lab with the goal of increasing their numbers. When given to a person, these cells can rapidly give rise to white blood cells and other components of the blood system,” said Delaney, who is also an assistant professor in the Department of Pediatrics at the University of Washington School of Medicine.
The current study also describes the outcomes of 10 patients in an ongoing phase 1 clinical trial who received two units of cord blood to treat high-risk, acute leukemia.
Each patient received one unit of non-manipulated cord blood and one in which the cells were expanded in the lab. Researchers evaluated the safety of infusing the expanded cells as well as how long it took to reconstitute the blood system, how durable the transplants were, and which cord blood unit contributed the most to engraftment. The age range of the patients was 3 to 43.
The results to date show that on average it took 14 days for the transplanted cells to engraft compared to an average of four weeks when non-expanded units of cord blood were used. Seven of the 10 patients are still alive with no evidence of disease and with sustained, complete engraftment. Tests revealed that the recovery of white blood cells early post transplant were derived predominantly from the expanded cord blood unit.
“For some AML remission and bone marrow transplant patients, receiving cord blood cells after chemotherapy may act as a bridge for bone marrow recovery,” Delaney says.
Most recent articles of interest
1. Gutman JA, Leisenring W, Appelbaum FR, Woolfrey AE, Delaney C, Low relapse without excessive transplant related mortality following myeloablative cord blood transplantation for acute leukemia in complete remission: a matched cohort analysis, Biol Blood Marrow Transplant. 2009 Sep;15(9):1122-9.
2. Delaney C, Gutman JA, Appelbaum FR, Cord Blood Transplantation for Hematologic Malignancies: Conditioning Regimens, Double Cord Transplant and Infectious Complications. British Journal of Hematology, 2009 Oct; 147(2):207-16.
3. Gutman JA, Turtle CJ, Manley TJ, Heimfeld S, Bernstein ID, Riddell SR, Delaney C. Single Unit Dominance Following Double Unit Umbilical Cord Blood Transplantation Coincides with a Specific CD8+ T Cell Response Against the Non-Engrafted Unit. (Plenary paper) Blood, 28 January 2010; Vol. 115, No. 4
4. Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger R and Bernstein ID. Notch-mediated Expansion of Human Cord Blood Progenitor Cells Capable of Rapid Myeloid Reconstitution. Nature Medicine, 17 January 2010 (Epub ahead of print).
Colleen Delaney, MD, an Assistant Member in Hutchinson Center’s Clinical Research Division, was awarded a $3.47 million grant under the American Recovery & Reinvestment Act of 2009. Her aim is to overcome the delay in neutrophil recovery following cord blood transplantation, with the ultimate goal of reducing the risk of infection and early death in cord blood transplant recipients. Dr. Delaney is responsible for a novel culture methodology that can significantly increase the number of cells available from a single unit of cord blood. When infused, these cells are capable of rapid recovery of neutrophils and could change the way transplants are done.
The Center for International Blood and Marrow Transplant Registry examined the survival rates of 8,847 transplants performed to treat blood cancers at U.S. centers in the National Marrow Donor Program (NMDP) network (www.marrow.org). The survival data was collected for the years 2002 through 2006 and patient outcomes were measured at the end of 2007. In each of five years, the Hutchinson Center “over performed” in terms of expected one-year survival rates after transplant. Only one other transplant center in the nation matched that record. The data was adjusted for several risk factors that could influence patient outcomes such as type of disease, its stage, patient age and degree of donor cell match.
The following five clinical trials are active and currently seeking pediatric patients. If you have a patient who may benefit from one of these clinical trials, please contact Ivy Riffkin, MN, RN in the Cord Blood Transplant Program at Fred Hutchinson Cancer Research Center at firstname.lastname@example.org or (206) 667-2587.
2010 Transplantation of Unrelated Umbilical Cord Blood for Patients with Hematological Diseases with Cyclophosphamide/ Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen
2044 A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors with an Unmanipulated Cord Blood Graft in Patients
2128 Multi-center, Open label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood Transplantation in Pediatric Patients with Leukemia and Myelodysplasia
2239 Transplantation of Unrelated Donor Umbilical Cord Blood in Patients with Hematological Malignancies Using a Reduced-intensity Preparative Regimen
2275 Transplantation of Unrelated Donor Umbilical Cord Blood in Patients with Hematological Malignancies Using a Treosulfan Based Preparative Regimen
If your patient is a candidate for transplantation, please contact the Transplant Program at Seattle Cancer Care Alliance for a consultation with one of our transplant specialists at (800) 804-8824. You may also refer your patients online at www.seattlecca.org/physician-referral.cfm.
PDF of Spring 2010 Pediatric Bone Marrow Transplant Newsletter
Pediatric BMT Newsletter
The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.
Read about important outcomes research at the Hutchinson Center that may benefit your patients.
Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.
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