The SAGE Encyclopedia of Stem Cell Research. Группа авторов
host immune system and subsequent integration of the stem cells. Although the use of myeloblative regimes are typical for less severe cases of hematological cancer, the benefits to more serious cases are largely unknown.
The current study will determine the rate of survival and progression following two years of transplantation. The study will look at the proportion of patients who achieve full donor chimerism after two years. The occurrence of possible clinically significant infections and engraftment of neutrophil and platelets after two years of transplant will be monitored by the study as well. Monitoring the rate of mortality and survival rate six months following nonmyeloablative conditioning is important in this study since the regime is normally not utilized in serious cases of hematological cancers. The incidence of acute or extensive chronic graft-versus-host disease will also be monitored after two years to help establish the effectiveness of the procedure.
Several clinical studies have found that infusion of unrelated donor stem cells that do not match exactly with those of the hematological cancer patient may help their bone marrow in producing stem cells and other types of blood cells. But the effectiveness and safety of such an approach is not fully characterized to allow routine usage in the clinics. With donor-matched stem cells, several risks will be averted, but the availability of these matched donors currently do not meet the demand. Transplanting stem cells that do not match patients has a higher likelihood of increasing the rejection and failure of these cell grafts; therefore, it is important to understand fully how the use of unrelated stem cells will react and work in patients if this method is allowed in the clinics.
Currently a phase II trial is investigating how unrelated umbilical cord blood transplanted to patients with hematological cancers works. To achieve this feat, unrelated donor stem cells will be transplanted to the patients and many indicators of effectiveness will be monitored. This will include overall survival, rate of progression-free survival, and occurrence of clinically relevant infections after two years.
In addition to monitoring neutrophil and platelet engraftment, the incidence of nonrelapse mortality will be monitored for six months, as will the incidence of chronic graft-versus-host disease and several stages of acute graft-versus-host disease. The progression of the cancer and graft rejection or failure will be examined following the transplant.
Preparative administration of rabbit antithymocyte globulin following transplantation of matched peripheral blood stem cells to optimize donor T-cell engraftment
Like the above, the use of stem cells in treating hematological cancer has been challenged by a high rate of rejection, infection, and graft failure. The use of pharmacological molecules in combination with stem cell transplantation has the potential to thwart these challenges and increase efficiency of the stem cell at the same time. For instance, preparative administration of rabbit antithymocyte globulin followed by cyclophosphamide, busulfan, and fludarabine before the stem cell transplant may help reduce the complications. There is a phase II trial currently investigating how well giving rabbit antithymocyte globulin together with a low intensity of cyclophosphamide, busulfan, or fludarabine before the transplantation of allogeneic peripheral blood stem cells will enhance engraftment of T-cells in patients with hematological cancer.
In most cases less than 50% of T-cell chimerism is achieved after stem cell transplant, hence the study will assess the percentage of patients in the study group that achieved up to 90% T-cell chimerism after one month of treatment with the above procedure. The overall safety, including transplant toxicity and tolerability of the drugs, and efficacy of the procedure will be assessed to determine the ability of the regimen to induce durable remissions in study patients. The study will monitor the incidence of chronic and acute graft-versus-host disease to determine how safe this procedure is in treating the patients.
The use of intrabone cord blood transplantation in treating hematological malignancies
Cord blood from unrelated donors is increasingly gaining the status of an alternative source of hematopoietic stem cells for adults with hematologic cancer who lack a human leukocyte-antigen (HLA)-matched donor. However, the utilization of single-unit cord blood for this purpose has been hampered by the low amount of nucleated cells in a single unit of cord blood. Researchers are looking at the potential of direct intrabone cord blood injection as a solution to the nucleated cell number problem, with the intention of minimizing nonspecific loss of progenitors. A phase I study and a phase II clinical trial are assessing the safety and efficacy of cord blood transplantation by intrabone cord blood injection in matured patients suffering from advanced or high-risk hematological cancer.
Application of irradiation to total marrow and lymph node combined with fludarabine and melphalan chemotherapy, and subsequent use of donor stem cells to treat patients with advanced hematological cancer
Though the use of a high-dose drug regime during transplantation of stem cells may reduce the problems associated with rejection and graft-versus-host disease, its use may have adverse fatal effects. Escalating doses of radiation therapy using helical tomotherapy in combination with fludarabine (FLU) and melphalan (MEL) as a preparative regimen for allogeneic hematopoietic stem cell transplantation in patients with advanced and hematological cancer who are not eligible for full myeloablative regimen may be beneficial. A phase I trial is investigating the side effects and best dose of total marrow and total lymph node irradiation. The trial seeks to test the maximum tolerable dose and intensity of modulated marrow and lymph node irradiation using tomotherapy. In addition, the toxicity, progression-free survival, and overall survival of this procedure is being tested. The frequency of acceptable clinical response, primary and secondary engraftment failure, time of neutrophil and platelet engraftment, and incidence of acute and chronic graft-versus-host disease will be studied in patients.
Haploidentical stem cell transplantation in patients with hematological
Approximately 71% of patients lacking HLA-identical siblings to donate stem cells for their transplant utilize haploidentical stem cells. However, there is a risk of more potent graft-versus-tumor effect and severe graft-versus-host disease that may be induced by this type of stem cell. There is a current trial investigating stem cell transplant using partially mismatched donor cells in treatment of hematological cancers. The investigators are hoping to test two kinds of transplants: a transplant with a full-intensity dose of radiotherapy and chemotherapy, and reduced-intensity doses of chemotherapy and radiotherapy. The study will be investigating the overall survival rate in patients with hematological cancers.
The use of escalating doses of selective inhibitor of nuclear export (KPT-330) in patients with advanced hematological cancers
A new phase I clinical trial aims to investigate the pharmacokinetics (how the body affects the concentrations of the drug in the blood) and pharmacodynamics (the effect of the drug on the body) of this small molecule inhibitor of nuclear export. The study will help determine the highest dose of KPT-330 that can be given safely and the side effects it may cause.
The study will also help to understand occurrence of adverse events, severity of the adverse events, and area under the plasma concentration versus time curve (AUC) of KPT-330, which will determine the change in AUC over time.
The use of sirolimus, tacrolimus, and thymoglobulin as graft-versus-host prophylaxis in hematological cancer patients undergoing unrelated donor hematopoietic cell transplantation
A phase II clinical trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in hematological cancer patients undergoing a donor stem cell transplant. The major aim of the study is to determine the incidence and severity of acute and chronic graft-versus-host disease. Other determinants to be monitored include the safety of this regime in the first six months after transplant, and the time before absolute neutrophil and platelet count recovery. The investigators will also monitor the participants after their first hospital discharge. In addition, the study will investigate the incidence of infections, particularly cytomegalovirus and Epstein-Barr virus reactivation, incidence of thrombotic