Hematopoietic Stem Cell Transplantation as Treatment for Type 1 Diabetes
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Type 1 diabetes mellitus is an autoimmune disease associated with B cell derived antibodies and T cell proliferative responses to a variety of islet cell peptides. Near normalization of blood sugar levels as monitored by glycosylated hemoglobin (HgbAlC) diminishes diabetic secondary complications. Insulin, while prolonging life, is not a cure and intensive insulin therapy to control blood sugar is not always practical, especially in lower economic classes or developing countries. Even in developed countries, serious sequela and mortality still occur. 1-5 In America, diabetes remains the most common cause of blindness and renal failure, and the sixth leading cause of death. Hematopoietic stem cell transplantation in early onset diabetes, and in established diabetes when combined with either pancreas or islet cell transplantation, offers hope of curing diabetes by reintroduction of islet cell tolerance.
STAT5-Mediated Self-Renewal of Normal and Leukemic Stem Cells
Jr., Richard H. Bell in JAK-STAT Pathway in Disease, 2006
Abstract he level of transcription factor activity critically regulates cell fate decisions such as he matopoietic stem cell self-renewal and differentiation. The balance between hematopoietic stem cell self-renewal and differentiation needs to be tightly controlled, as a shift towards differentiation might exhaust the stem cell pool while a shift towards self-renewal might mark the onset of leukemic transformation. A number of transcription factors have been proposed to be critically involved in governing stem cell fate and lineage commitment, such as HOX transcription factors, c-Myc, Notchl, P-Catenin, C/EBPa, PU.l and STATS. It is therefore no surprise that dysregulation of these transcription factors can also contribute to the development of leukemias. This review will discuss the role of STAT 5 in both normal and leukemic hematopoietic stem cells as well as mechanisms by which STAT5 can contribute to the development of human leukemias.
Gene Transfer into Human Hematopoietic Stem Cells
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Manipulations with hematopoietic stem cells (HSC) in the context of bone marrow or peripheral blood stem cell transplantation have become a routine procedure. 1 , 2 Preparative quantities of HSC are readily accessibile. Either marrow or peripheral blood can provide greater than 2 million CD34 + HSC per kilogram of donor weight per harvest or apheresis, respectively. Using human HSC surface markers such as CD34 or AC 133, it is possible to separate and enrich for HSC ex vivo. The intrinsic properties of HSC make them attractive targets for gene transfer. Gene modified HSC should achieve long-term repopulation in the recipient with equally long-term transgene expression. 3 Nowadays the gene transfer into hematopoietic cells comprises 7.4% (44 protocols) of the total number of United States Food and Drug Administration (FDA) approved gene therapy clinical trials.
Autologous hematopoietic stem cell transplantation for pediatric solid tumors
Published in Expert Review of Anticancer Therapy, 2005
While advances in the treatment of pediatric cancers have increased cure rates, children with metastatic or recurrent solid tumors have a dismal prognosis despite initial transient responses to therapy. Autologous hematopoietic stem cell transplantation takes advantage of the steep dose–response relationship observed with many chemotherapeutic agents. While clearly demonstrated to improve outcomes in patients with metastatic neuroblastoma, autologous hematopoietic stem cell transplantation is also frequently used to treat patients with other high-risk diseases such as Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, retinoblastoma, germ cell tumors, lymphomas and brain tumors. Most published experience consists of retrospective, single-arm studies; randomized clinical trials are lacking, due in part to the rarity of pediatric cancers treatable by autologous hematopoietic stem cell transplantation. These published literature demonstrate that autologous hematopoietic stem cell transplantation results in most cases in equivalent or superior outcomes when compared with conventional therapies. However, patient heterogeneity, patient selection, graft characteristics and processing and the varied conditioning regimens are additional factors to consider. Since the inception of autologous hematopoietic stem cell transplantation, regimen-related toxicity has markedly decreased and the vast majority of treatment failures are now due to disease recurrence. Prospective clinical trials are needed to identify specific high-risk patient populations, with randomization (when possible) to compare outcomes of patients undergoing autologous hematopoietic stem cell transplantation with those receiving standard therapy. In addition, investigators need to better define the role of autologous hematopoietic stem cell transplantation in these solid tumors, particularly in combination with other therapeutic modalities such as immunotherapy and novel cell processing methodologies.
Autologous hematopoietic stem cell transplant in first remission in non-Hodgkin’s lymphoma
Published in Expert Review of Anticancer Therapy, 2003
The PARMA trial clarified the role of hematopoietic stem cell transplant in patients with non-Hodgkin’s lymphoma in chemotherapy-sensitive relapse. With the goal of improving overall response and survival rates, hematopoietic stem cell transplant has been incorporated into the front-line treatment plan in some studies. While multiple clinical trials have been designed to address this issue, they have varied in their treatment regimens, patient populations and outcomes. This review will summarize and analyze the data obtained so far and provide practitioners with recommendations for the application of high-dose chemotherapy and hematopoietic stem cell transplant as part of the initial treatment of patients with both indolent and aggressive non-Hodgkin’s lymphoma. Based upon the current literature, hematopoietic stem cell transplant cannot be recommended as first-line therapy in patients with non-Hodgkin’s lymphoma outside the setting of a clinical trial.
Revisiting the role of hematopoietic stem cell transplantation in chronic lymphocytic leukemia
Published in Expert Review of Anticancer Therapy, 2005
Edgardo S Santos, Mohamad Masri, Hana Safah
Since the advent of hematopoietic stem cell transplantation more than 40 years ago, numerous methods of transplantation have been developed, modified and improved upon. Although hematopoietic stem cell transplantation has been used in a variety of malignant diseases since then, its use in the treatment of chronic lymphocytic leukemia has recently started to gain interest. Patients with chronic lymphocytic leukemia are generally elderly, and because of its relatively benign course, they were not considered suitable candidates for hematopoietic stem cell transplantation. Nonetheless, there have been marked improvements in transplantation techniques, including better conditioning regimens that have decreased treatment-related morbidity and mortality. In this article, the authors review the most recent data on hematopoietic stem cell transplantation in chronic lymphocytic leukemia as well as the change in risk stratification based on newer prognostic factors and its impact on treatment decisions in chronic lymphocytic leukemia.