Another trial is currently recruiting patients for “allogeneic hematopoietic stem cell transplant for patients with primary immune deficiencies.” The implementation of four regimens using different combinations of drugs adds to the complexity of this clinical trial. The most appropriate regimen for the patient will be determined based on the diagnosis and clinical history. The regimens comprise Arm A: Fully Myeloablative Preparative Regimen, Arm B: Reduced Toxicity Ablative Preparative Regimen, Arm C: Reduced Intensity Conditioning, and Arm D: No Preparative Regimen.
The registry of clinical trials at the U.S. National Institutes of Health lists 1,428 studies involving stem cells for the treatment of immunologic disorders. They involve a combination of various regimes such as total body irradiation, chemotherapy drugs and bone marrow or peripheral blood stem cell transplantation in patients with autoimmune disorders, systemic lupus erythematosus, human immunodeficiency virus, and severe combined immunodeficiency. The employment of autologous stem cell transplantation for Crohn’s disease and umbilical cord blood stem cells in adults with advanced blood disorders or cancer are also being studied. The efficacy of specific drugs in preventing/controlling GVHD is also being assessed.
The rarity of the disease in combination with a lack of awareness among both physicians and patients are obstacles to the success of clinical research in histiocytic disorders. Patients are unfamiliar with the concept and are reluctant to act as guinea pigs for experimental procedures. Physicians on the other hand may not be willing to put in the time and effort required to plan, conduct, and consolidate the results of a rigorous clinical trial. Some clinical trials are conducted with a small number of patients and the results may not be statistically significant.
However, improved and tested treatment regimes and techniques such as myeloablative chemotherapy (reduced/complete depletion of bone marrow cells) followed by stem cell transplantation have improved the prognosis of patients with immunologic and histiocytic disorders. Future research needs to focus on improving the quality of life and life span of patients with severe and progressive histiocytic disorders involving high-risk organs such as the lungs, the central nervous system, and the liver. Agents to reduce fibrosis and neurodegeneration need to be identified and studied.
Ruby A. Singh
Independent Scholar
See Also: Blood Adult Stem Cell; Current Research on Isolation or Production of Therapeutic Cells; Blood Adult Stem Cell: Development and Regeneration Potential; Bone: Current Research on Isolation or Production of Therapeutic Cells.
Further Readings
Gadner, H., N. Grois, U. Potschger, et al. “Improved Outcome in Multisystem Langerhans Cell Histiocytosis Is Associated With Therapy Intensification.” Blood, v.111 (2008).
Vaiselbuh, S. R., Y. T. Bryceson, C. E. Allen, J. A. Whitlock, and O. Abla. “Updates on Histiocytic Disorders.” Pediatric Blood Cancer (March 9, 2014).
Weitzman, Sheila and Maarten R. Egeler, eds. Histiocytic Disorders of Children and Adults: Basic Science, Clinical Features and Therapy. Cambridge: Cambridge University Press, 2005.
Clinical Trials, U.S.: Kidney Disease
Clinical Trials, U.S.: Kidney Disease
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Clinical Trials, U.S.: Kidney Disease
The advent of cell-based therapies has changed the traditional view regarding organs having limited capacities for regeneration. Stem cells are currently viewed as the solution to a wide range of diseases that are generally characterized with damaged or dysfunctional cells and tissues. The introduction of stem cells to specific organs of the body for differentiation, as well as replacement or repair of diseased tissues, is based on their inherent plasticity, allowing them to perform an array of cellular functions. In the area of kidney diseases and disorders, stem cells are regarded as key structures that could serve as mechanisms for their natural repair and prevent further progression of renal diseases.
For centuries, the biomedical field has considered vital organs of the body as fully differentiated groups of tissues that have no capacity for regenerating their constituent cells. However, the discovery of stem cells and their ability to self-renew has not only changed the views of organ physiology and treatment paradigms but also triggered a new biomedical field now known as regenerative medicine. For example, the increase in the functional demand of the kidney has long been considered to result in hypertrophy of renal cells. For decades, patients diagnosed with kidney failure have required renal transplants in order to continue the body’s requirement of cleansing its bodily fluids. However, initial experiments conducted several decades ago involving animal models have shown that bone marrow–derived stem cells could be used to replace damaged renal cells. This observed plasticity was thus further examined using more extensive research studies using various types of stem cells.
The Application of Stem Cells in Kidney Diseases
The potential application of cell-based therapies to kidney diseases appears to be more significant than that to other diseases because its incidence has been increasing in the past few decades. Furthermore, kidney diseases are strongly associated with various medical conditions that are also increasing in prevalence, including cardiovascular diseases, as well as metabolic syndromes including obesity and diabetes. Amid the significant improvement in treatment strategies for various chronic medical conditions, the morbidity and mortality rate of kidney disease has been constant, thus prompting the need to identify a more effective approach to its prevention and treatment. Epidemiological studies have shown that the survival rate of a patient with end-stage renal disease is significantly lower than a patient diagnosed with prostate cancer.
One of the major factors influencing the increase in the incidence and the stagnant morbidity and mortality of kidney disease is the lack of novel treatment regimens for this condition. For decades, the same therapeutic formulations for cardiovascular diseases that strongly influence the development of kidney disease have been used, which include statins, angiotensin converting-enzyme inhibitors, and aspirin. Problems relating to the utilization of these drugs have also been a problem. Treatment options for impending kidney problems stemming from cardiovascular conditions include kidney transplantations and dialysis; however, the patient outcomes often vary depending on the skills of the attending physician as well as the number of available matching kidney donors. This unmet need for an effective treatment scheme for kidney disease has thus existed for decades.
The use of bone marrow–derived stem cells for the treatment of kidney diseases has emerged from the principle that these pluripotent cells possess the capacity to promote tissue repair, particularly in cases of acute renal failure. In the case of kidney disease, renal cells undergo ischemia due to damages inflicted by toxins such as antibiotic and chemotherapeutic drugs, as well as other immune factors. The damaged nephrons are thus unable to further function in the kidney, often resulting in other systemic diseases and multiple organ failure. Acute renal failure is also associated with the loss of epithelial cells of the renal tubules, mainly through the process of necrosis. This early form of tissue damage can result in edema in a patient, together with microvascular problems relating to perfusion or inability to promote the flow of toxins out of the body.
The introduction of bone marrow–derived stem cells for the treatment of acute renal failure is expected to enhance the repair of damaged ischemic cells of the renal tubules, thus increasing patient survival. The administration of bone marrow–derived stem cells also decreases the production of interleukin-6 levels, which are strongly associated with atherosclerosis and serve as an indicator of inflammation. This reduction in cytokine production may then facilitate the shift toward tissue