ABSTRACT
Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαß and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αß/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαß+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαß/CD19-depleted grafts represents a viable treatment option.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Antigens, CD19 , Child , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Lymphocyte Depletion/methods , Prospective Studies , Receptors, Antigen, T-Cell, alpha-beta , Transplantation Conditioning/methodsABSTRACT
Stem cells have the potential to revolutionize tissue regeneration and engineering. Both general types of stem cells, those with pluripotent differentiation potential as well as those with multipotent differentiation potential, are of equal interest. They are important tools to further understanding of general cellular processes, to refine industrial applications for drug target discovery and predictive toxicology, and to gain more insights into their potential for tissue regeneration. This chapter provides an overview of existing sorting technologies and protocols, outlines the phenotypic characteristics of a number of different stem cells, and summarizes their potential clinical applications.
