Hematopoietic cell transplantation (HCT), the transplantation of blood-forming stem cells from the bone marrow, peripheral blood, or umbilical cord blood, is the primary option for treatment for many patients who suffer from various hematologic disorders, including blood cancers, sickle cell disease, bone marrow deficiencies, bleeding disorders, and autoimmune disorders. Research investigating breakthroughs in hematopoietic cell transplantation will be presented today at the 53rd Annual Meeting of the American Society of Hematology.
"The studies that will be presented today demonstrate the major advances underway in the field of hematopoietic cell transplantation," said Stephanie J. Lee, MD, MPH, moderator of the press conference and Professor of Medicine at the University of Washington School of Medicine in Seattle. "Although hematopoietic cell transplantation is considered a standard approach for treating blood disorders, there are still many complications involved, underscoring the continual need for novel research that can improve survival rates and quality of life for patients who undergo these procedures."
This press conference will take place on Saturday, December 10, at 11:00 a.m. PST.
Increased Incidence of Chronic Graft-Versus-Host Disease (GVHD) and No Survival Advantage with Filgrastim-Mobilized Peripheral Blood Stem Cells (PBSC) Compared to Bone Marrow (BM) Transplants From Unrelated Donors: Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0201, a Phase III, Prospective, Randomized Trial [Abstract 1]
A new study reveals that peripheral blood stem cell (PBSC) transplants from unrelated donors are associated with higher rates of chronic graft-versus-host-disease (GVHD) and have no survival advantage when compared to transplants using stem cells taken from the bone marrow.
PBSCs are stem cells originally found in the bone marrow that have been moved, or mobilized, into the blood stream by a special drug regimen. Unlike bone marrow stem cells, which must be extracted from the bones in an operating room, PBSCs are more easily obtained through apheresis, a process similar to regular blood donation, which collects the PBSCs through a tube inserted in a vein. A critical step before the transplant is to find a donor that is tissue matched to the recipient.
About one-third of patients who need a PBSC or bone marrow transplant for treatment of a blood disease have a matched, related donor. According to the National Marrow Donor Program, of the 70 percent who cannot find a donor within their family, most will be able to find an unrelated donor. Since the majority of transplant patients ultimately receive cells from unrelated donors, there is a need to better understand the risks associated with transplants of unrelated donor cells.
Previous clinical trials on related donor transplants have demonstrated that PBSC transplants in patients with leukemia and other blood diseases result in better engraftment, lower relapse rates, and increased survival compared to transplants with bone marrow stem cells. However, those trials also found that PBSC transplants carry an increased risk of GVHD, a serious and often deadly post-transplant complication that occurs when the newly transplanted donor cells recognize the recipient's own cells as foreign and attack them. Patients who survive early post-transplant may develop chronic GVHD, a disabling condition managed with long-term immunosuppressant therapy.
Many transplant centers are increasingly using PBSCs as a source for adult stem cells because of their superiority in clinical trials that have directly compared outcomes between PBSCs and bone marrow stem cells from related donors. However, to date, there has not been a comparative study of the two transplant sources that has prospectively analyzed patient outcomes in unrelated donor transplants.
To determine whether graft source – PBSCs or bone marrow – affects transplant outcomes in unrelated donor transplants for patients with leukemia or other hematologic malignancies, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducted a clinical trial, BMT CTN Protocol 0201, to compare two-year survival probabilities for patients transplanted with PBSCs or bone marrow stem cells from unrelated donors. Fifty transplant centers in the United States and Canada participated in this large, Phase III, prospective, multicenter study which randomized patients to receive bone marrow>
According to the trial analyses, there were no observed differences in overall survival, relapse, non-relapse mortality, or acute GVHD between the patients receiving PBSCs or bone marrow stem cells from unrelated donors. While engraftment was faster in patients receiving PBSCs, there was a higher incidence of overall chronic GVHD in these patients (53%) than in those transplanted with bone marrow stem cells (40%). Patients receiving transplants of PBSCs from unrelated donors also had a higher incidence of chronic extensive GVHD (46%) than patients who received bone marrow stem cells (31%).
"Although PBSCs from related donors have demonstrated clinical benefits, our trial demonstrates that when these stem cells originate from unrelated donors they are not superior to bone marrow stem cells in terms of patient survival, and they increase the risk for chronic GVHD," said lead author Claudio Anasetti, MD, Chair of the Department of Blood & Marrow Transplant at Moffitt Cancer Center in Tampa, Fla. "More effective strategies to prevent GVHD are needed to improve outcomes for all patients receiving unrelated donor transplants."
This trial was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Dr. Anasetti will present this study during the Plenary Scientific Session on Sunday, December 11, at 2:05 p.m. PST at the San Diego Convention Center in Hall AB.
Burden of Morbidity in 10+ Year Survivors of Hematopoietic Cell Transplantation (HCT): A Report From the Bone Marrow Transplant Survivor Study (BMTSS) [Abstract 841]
New research concludes that long-term (10 or more years) survivors of hematopoietic cell transplant (HCT), when compared to their siblings, have a higher risk of psychological and chronic health conditions, including heart attack, stroke, diabetes, subsequent cancers, and long-term generalized pain or discomfort referred to as somatic distress.
While HCT is a life-saving treatment for patients with blood disorders, it is often accompanied by an increased risk of long-term physical complications such as infections, relapse, and GVHD. High-intensity conditioning regimens and powerful immunosuppressant medications given to recipients to prepare the body to receive donor cells and prevent rejection can have a variety of negative side effects. In addition to these complications, recent research has found that the psychological health of HCT survivors is also affected.
"Although previous research has shown that morbidity increases with length of survival after an HCT, this is the first study to specifically examine the burden of morbidity in those who have survived 10 or more years after a transplant," said lead author Can-Lan Sun, PhD, Associate Research Professor at City of Hope in Duarte, Calif.
To study late medical effects and quality of life in HCT survivors, researchers analyzed patient data from 366 10-or-more-year HCT survivors and their 309 siblings from the Bone Marrow Transplant Survivor Study, the largest of its kind to date. Survivors and their siblings were evaluated for the presence of any chronic conditions, which were given a severity score from 1 (mild) to 5 (death due to condition), as well as any psychological conditions, including somatic distress, anxiety, and depression. The current status of health-care utilization by survivors, an estimated figure accounting for frequency of visits to doctors, hospitalizations, and other factors, was also evaluated.
Results from the analysis revealed that nearly three-fourths (74%) of HCT survivors reported at least one chronic health condition over the 15-year follow-up period, compared with 29 percent of siblings. Additionally, one-fourth of survivors reported severe or life-threatening conditions compared to only 8 percent of siblings. Commonly reported severe or life-threatening chronic health conditions included heart attack, stroke, blindness, diabetes, musculoskeletal problems, and subsequent cancers. The 15-year cumulative incidence of any chronic health conditions in survivors was 71 percent, while the incidence of particularly severe or life-threatening conditions or death was 40 percent. Investigators also found that HCT survivors were nearly six times more likely than their age- and sex-matched siblings to develop a severe or life-threatening condition.
While prevalence of anxiety and depression were comparable between the two groups, HCT survivors were nearly three times more likely than their siblings to report somatic distress. Approximately 90 percent of HCT survivors reported having health insurance; a high proportion needed ongoing specialized medical care. Nearly two-thirds (61%) of survivors reported a cancer- or HCT-related visit to a specialist at an average of 15 years after transplant.
"The long-term physical and psychological burden of HCT on survivors is substantial, resulting in high usage of specialized health care among this population," said senior author Smita Bhatia, MD, MPH, Director of the Center for Cancer Survivorship and BMT Long-Term Follow-up Program and Ruth Ziegler Chair in Population Sciences at City of Hope in Duarte, Calif. "Patients, families, and health-care providers need to be made aware of this high burden so they can plan for post-HCT care, even many years after transplant."
Dr. Sun will present this study in an oral presentation on Monday, December 12, at 4:30 p.m. PST at the Manchester Grand Hyatt in the Elizabeth Ballroom FG.
Over-Expression of TRAIL on Donor T-Cells Enhances GVT and Suppresses GVHD Via Elimination of Alloreactive T-Cells and Host APC [Abstract 817]
Scientists have discovered a method of using genetically engineered T-cells to help the body kill cancer cells more effectively without causing a deadly post-transplant complication.
One of the reasons cancer cells are able to grow, multiply, and spread so quickly is that the body recognizes them as normal, rather than diseased. Patients with blood cancers often receive a transplant of healthy hematopoietic, or blood-forming, stem cells to help attack cancer cells, called hematopoietic cell transplantation (HCT). When these immune system cells found in the bone marrow are transplanted from a healthy donor to a cancer patient, donor cells may recognize the cancer cells in the recipient's body and attack them, a desirable phenomenon known as the graft-versus-tumor (GVT) effect. However, one of the challenges of HCT is the risk for graft-versus-host disease (GVHD), a serious and often deadly post-transplant complication which occurs when the donor cells attack the recipient's healthy cells instead.
To combat GVHD, doctors administer powerful medications to suppress the immune system. While these medications reduce the probability of GVHD, they can also reduce the GVT effect. Recognizing this challenge, researchers sought to create a new method to suppress GVHD without compromising the GVT effect by using genetically engineered donor T-cells that over-express a protein known to induce cell death in an effort to specifically attack cancer cells.
The protein, Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand, or TRAIL, is naturally expressed on some immune cells in the body. TRAIL targets tumor cells and keeps them from multiplying and spreading by interacting with death receptor molecules, which are highly expressed on the surface of tumor cells, making them more susceptible to therapeutic targeting using TRAIL.