Ex Vivo Expanded (EVE) Megakaryocytes (MK) for Supportive Care of Patients With Breast Cancer Hematologic Malignancies: A Phase I/II Clinical Study

摘要

The main goal of this project is to culture blood stem cells in the presence of human hematopoletic growth factors to produce autologous megakaryocytes (MK) to be transfused into patients as a supplement to the conventional stem cell autograft. The purpose of the clinical trial is to determine whether the transfused MK will generate platelets in vivo in great enough numbers to reduce or eliminate the need for repeated platelet transfusions following high-dose chemotherapy and autologous stem cell transplant. We determined in pre-clinical experiments that a cocktail of the growth factors thrombopoietin, IL-3 and Flt3-L and high seeding cell density were necessary to optimize the ex vivo expansion of MK. We successfully transplanted three patients. Cell expansion was optimal after six days, no negative reactions were observed, and the patients recovered normal platelet levels fast with normal platelet function. This study shows that using an ex vivo expanded product is feasible, and the successful outcome in our three transplanted patients augurs well for future use of this concept. Additionally, we have added a novel survival factor, PLP-E to the arsenal of growth factors used for ex vivo myeloid expansion and have elucidate the molecular mechanism of proplatelet formation.