Stem Cell Transplant Therapy

Advances in stem cell therapy have received a great deal of press in recent years. Unfortunately, when public expectations have been raised, patients are likely to search for non-orthodox sources of treatment. There are tens of thousands of internet pages extolling the promise of stem cells, and various forms of stem cell therapy are available on a commercial basis in a number of countries, including China, South America, and Eastern Europe. However, most administer the stem cells in an uncontrolled way and do not have long term follow-up so that rational scientific conclusions cannot be reached. The science provides hope for potential therapeutic interventions in neurodegenerative diseases, but it is in its early stages and much is still needed to be learned about how to control stem cell proliferation, differentiation into specific cells and optimal functional recovery in animal models before human trials. The collection and use of human fetal tissue may also raise ethical concerns. 

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Wliich is not a complication for embryonic or fetal stem cell transplant therapy ... 

HF due to ischemic heart disease is one of the leading causes of worldwide mortality. While current clinical therapies can improve hemodynamics in HF, currently there is no viable option for replacing damaged cardiac muscle cells. Stem cell transplantation therapy offers tremendous potential to regenerate the myocardium and improve overall quality of life. However, there are several critical challenges with stem cell transplantation such as poor cell retention at the site of transplantation, survival, and eventual functional integration into the diseased tissue. Various natural and synthetic biomaterials have been explored to enhance cell retention and survival in the ischemic myocardium, and ultimately... 

Allogeneic hematopoietic stem cell transplantation (HSCT) has been used in the treatment of pediatric AML in first complete remission. In most clinical trials, the availability of HLA-matched sibling donors determined whether patients underwent HSCT as postremission treatment. To facilitate this process, it is important to obtain HLA typing on all younger patients with AML and siblings shortly after diagnosis. Patients who do not have an HLA-matched sibling will proceed to postremission therapy. 

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

Allogeneic hematopoietic stem cell transplantation is the only therapy that is curative. The best candidates are younger than 16 years of age, have severe complications, and have human leukocyte antigen-matched donors. Risks must be carefully considered and include mortality, graft rejection, and secondary malignancies. 

Patients who relapse after an initial complete response can be treated with the same regimen, a non-cross-resistant regimen, radiation therapy, or high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). 

A drawback for stem cell therapy is the problem of cell rejection due to the host s immune system recognizing the cells as foreign. This rejection issue has to be overcome to ensure stem cell therapy is a viable treatment. Recently, French scientists reported on research progress in stem cell transplants for curing children with sickle cell anemia. A mix of antirejection drugs was used to suppress rejection of the new stem cells. 

Although research into stem cells is new, the use of stem cells for therapy has been with us for some time. Most of us are familiar with bone marrow transplant for patients with leukemia. This procedure involves finding a matching donor to harvest bone marrow stem cells and transfuse them into the patient with leukemia (see Exhibit 4.16 for details). 

Figure 1. Shaping the T cell repertoire in hemopoetic stem cell transplantation and immnno-therapy of malignant disease by T cell antigen receptor transfer.

Giles FJ, Kantarjian HM, Komblau SM, Thomas DA, Garcia-Manero G Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH. (2001) Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 92 406-413. 

Expanded hematopoietic (stem and progenitor) cells have widespread potential in therapy and this will only be briefly described here. For a comprehensive overview, the review by Schindhelm and Nordon [27] is recommended. Potential applications include graft engineering in stem cell transplantation [24], gene and immunotherapy and the production of mature blood cells for transfusion medicine. 

Therapy, when replacement of the marrow by allogeneic haematopoietic stem cell transplantation is not possible, comprises 500 mg of methylpred-nisolone by 8 hour intravenous infusion repeated for five consecutive days. Concurrently 15 mg/kg of antilymphocyte or antithymocyte globulin is given... 

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