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 microangiopathy, incidence of disease relapse, and the incidence of post-transplant lymphoproliferative disease. Moreover, the study will determine nonrelapse mortality at 100 days and one year past hematopoietic stem cell transplantation (HSCT), as well as overall and disease-free survival at one year post-HSC transplant.
In general, most of the clinical trials going on in the United States for the treatment of hematological cancers are stem cell based, particularly the use of hematopoietic stem cells. Current clinical trials on hematological cancer treatments are directed toward extending the benefits of stem cell to more categories of patients. These approaches include the use of stem cell transplant with less intensity of chemotherapy regimens, which will allow use in patients that may be too sick or old. The use of haploidentical or partially matched cord blood will allow patients who do not have an available matched sibling to utilize transplantation. These trials are exploring pharmacological manipulation and selection of donor stem cells, which will help increase better outcomes and reduce complications. These trials are especially important in adult bone marrow transplant, since fewer than 25% of adult patients have access to matched donors.
Chinedu Anthony Anene
Bradford University School of Management
See Also: Bone Marrow Transplants; Clinical Trials, U.S.: Graft Failure, Graft-Versus-Host Disease; Hematopoietic Transplantation: Cancer.
Further Readings
Ema, H., H. Takano, K. Sudo, et al. “In Vitro Self-Renewal Division of Hematopoietic Stem Cells.” Journal of Experimental Medicine, v.192 (2000).
Gallacher, L., B. Murdoch, D. Wu, et al. “Identification of Novel Circulating Human Embryonic Blood Stem Cells.” Blood, v.96 (2000).
Glimm, H., I. H. Oh, and C. J. Eaves. “Human Hematopoietic Stem Cells Stimulated to Proliferate In Vitro Lose Engraftment Potential During Their S/G (2)/M Transit and Do Not Reenter G(0).” Blood, v.96 (2000).
Clinical Trials, U.S.: Immunologic/Histiocytic Disorders
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Clinical Trials, U.S.: Immunologic/Histiocytic Disorders
The immune system has been the focus of rapid and exciting research over the last decade. An overactive and misguided immune system stimulates the development of autoimmune disorders, whereas primary/acquired immunodeficiency disorders result from a sluggish functioning of the system. The system is also known to mount abnormal and sometimes severe allergic responses to harmless antigens in the environment.
Histiocytic disorders, on the other hand, are a category of rare and therefore poorly understood and difficult to diagnose and treat diseases of cells of the innate immune system known as histiocytes. Histiocytes
