the improvement in the recovery of the immune system after undergoing HSCT. Restoring the condition of the immune system, particularly in terms of eliciting an immune response that is mediated by T cells, is an essential feature of a competent and active immune system. Initially, T cells are regenerated using the donor’s T cells from peripheral blood. However, subsequent regeneration of T cells occurs in the patient’s body through the process of neogenesis. The rate of T cell regeneration generally varies with the age of the patient, and earlier studies have shown that older patients are more likely to experience a delay in immune recovery. In addition, intensive applications of preconditioning chemotherapeutics can further delay the generation of new T cells. The occurrence of GVHD also decreases the chances of achieving immune recovery at a faster rate.
A clinical trial was thus conducted to monitor the number of donor lymphocyte counts in patients who underwent HSCT in order to establish the influence of specific T cell populations in immune recovery, as well as in the outcome of the transplant procedure. The study population consisted of a total of 220 HSCT patients who have been previously diagnosed with various hematologic cancers. These patients received mobilized hematopoietic stem cells that were HLA-matched with their sibling donors. CD4+ T cells were monitored as indicators of patient survival, as well as chronic GVHD; these cells comprise a subset of T regulatory cells that are responsible in the development of GVHD.
One novel finding of this clinical trial is that when the number of CD4+ T cells was relatively high, patient survival increased, regardless of the age of the recipient patient or the relative donor. This study also emphasized that the quality of the donor tissue is more important than the potential amount of tissue that could be used during an HSCT. However, the proponents of this study explained that it might be possible that these superb outcomes were observed because all donor-recipient pairs consisted of siblings who are HLA-matched and thus it does not provide assurance that the same results could be achieved using mismatched siblings or transplants with low T cell counts.
The Promise of HSCT in Hematologic Malignancies
Current trends in the treatment of hematologic malignancies include the use of standard chemotherapeutic regimens such as anticancer drugs. However, this approach can only be conducted as long as the patient is showing a response to the treatment. In the event that a patient does not respond to a particular drug, then there is a potential that the patient might be a good candidate for a clinical trial. Patients who are classified as being high risk are offered discussions of their options of using HSCT. The goals of HSCT may vary among patients and thus the optimal scheme for these types of malignancies is to identify a scheme that would be effective in preventing further progression of the disease without resulting in adverse reactions in the patient.
Rhea U. Vallente
Independent Scholar
See Also: Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies; Clinical Trials, U.S.: Graft Failure, Graft-Versus-Host Disease.
Further Readings
Choi, S.W., T. Braun, L. Chang, L., J. L. M. Ferrara, et al. “Vorinostat Plus Tacrolimus and Mycophenolate to Prevent Graft-Versus-Host Disease After Related-Donor Reduced-Intensity Conditioning Allogeneic Haemopoietic Stem-Cell Transplantation: A Phase 1/2 Trial.” Lancet Oncology, v.15 (2014).
Fruehauf, S., G. Ehninger, K. Hubel, J. Toplay, et al. “Mobilization of Peripheral Blood Stem Cells for Autologous Transplant in Non-Hodgkin’s Lymphoma and Multiple Myeloma Patients by Plerixafor and G-CSF and Detection of Tumor Cell Mobilization by PCR in Multiple Myeloma Patients.” Bone Marrow Transplantation, v.45 (2010).
Güngör, T., P. Teira, M. Slatter, G. Stussi, et al., on behalf of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. “Reduced-Intensity Conditioning and HLA-Matched Haemopoietic Stem-Cell Transplantation in Patients With Chronic Granulomatous Disease: A Prospective Multicentre Study.” Lancet, v.383 (2014).
Solomon, S. R., S. Mielke, B. N. Savani, A. Montero, et al. “Selective Depletion of Alloreactive Donor Lymphocytes: A Novel Method to Reduce the Severity of Graft-Versus-Host Disease in Older Patients Undergoing Matched Sibling Donor Stem Cell Transplantation.” Blood, v.106 (2005).
Clinical Trials, U.S.: Crohn’s Disease
Clinical Trials, U.S.: Crohn’s Disease
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Clinical Trials, U.S.: Crohn’s Disease
Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract with many extra intestinal manifestations as well. It can affect any part of the digestive tract, from oral cavity to anal canal. The most common site of involvement is the small bowel, and in particular, the ileum. It usually presents with abdominal pain, diarrhea (at times bloody), weight loss, and fever. Extraintestinal manifestations include joint and skin problems.
Presented in a paper by Burrill Bernard Crohn and colleagues for the first time in 1932, the etiology of disease is not clear to date. In the United States, around 1.4 million people suffer from the disease. Many treatment regimens are emerging in an effort to find a cure to decrease the disease burden and reduce its complications. Regenerative medicine and stem cell therapy is very important, as scientists are able to understand the healing ability of the human body. This article focuses on the role of stem cell therapy in the treatment of Crohn’s disease, with emphasis on clinical trials performed in the United States.
Stem Cell Therapy
The exact etiology is not known, but involvement of the immune system, genetics, and environmental factors have been proposed. Current treatment options for Crohn’s include immunosuppressants, antibiotics, and surgery for related complications. Since conventional treatment methods are not promising, stem cell therapy has emerged to produce fruitful outcomes, with complete remission seen in recent clinical trials. In 2009, the FDA approved the first human trial using embryonic stem cells. Administration of stem cell therapies derived from adult hematopoietic, mesenchymal, and adipose tissue have been attempted. Hematopoietic stem cells produce all different blood cells, including the white blood cells that form the immune system. Because Crohn’s is caused by an exaggerated immune response, replacing the overactive immune system with a new immune system using hematopoietic stem cells could counteract this problem, but controversies still exist regarding long-term efficacy and safety. Mesenchymal stem cells are connective tissue stem cells that can generate a variety of supportive cell types and have potent immunosuppressive properties. Treatment of fistulizing Crohn’s disease with mesenchymal stem cells has shown favorable results in the latest clinical trials.
Clinical Trials in the United States
According to William Katkov, MD, methods to grow intestinal cells in lab settings have been discovered, and it is possible to generate different cell types from mature intestinal cells. In mice models, cells can patch the ulcerated lesion, thereby protecting the lesion while the intestine heals. Efficacy remains to be proven in humans.
In California, autologous hematopoietic stem cell transplantation (HSCT) for Crohn’s disease treatment was carried out to evaluate the safety and potential clinical benefits of lymphoablation followed by autologous HSCT rescue in therapy-refractive Crohn’s disease. In addition, autologous adipose tissue–derived stem cell (ASC) treatment was shown to be promising to manage
