SAFETY AND EFFICACY EVALUATION OF EX VIVO EXPANDED CORD BLOOD PROGENITOR CELLS FOR ALLOGENIC TRANSPLANTATION IN A PHASE I/II STUDY

Therapeutic use of cord blood (CB) is limited by low numbers of hematopoietic progenitor cells (HPCs). We developed a clinical system to expand CB HPCs using interleukin‐6, stem cell factor, Flt3 ligand and thrombopoietin, in serum‐free medium and 10% AB allogeneic plasma. After immunoselection, CD34+ cells are cultured for 2 weeks and cytokines replaced twice a week. To evaluate the safety and efficacy of this experimental approach, we developed a phase I/II trial for allogeneic transplantation of expanded CB HPCs. For safety reasons, only 1/3 of the CB unit is thawed, immunoselected and expanded. The negative fraction after CD34+ selection, that contains the T cells, is thereafter transplanted, together with the unmanipulated and expanded cells. Two children with thalassemia and sickle cell disease and one child with refractory anemia, have been already transplanted. The mean±SD fold expansion of CD34+ cells were 48±15. The expanded grafts included 11.7±1.8x10E6 CD34+ and 1.8±0.7x10E6 CD61± cells and had a low lymphocyte content (CD3+ cells 2.5±1.3 x10E4). The neutrophil and platelet engraftment time was 18±3 and 32±8 days respectively. The patients are alive and well at 15, 8 and 5 months post‐transplant. These results indicate that our system is capable to efficiently and safely expand CB HPCs thus accelerating the hematopoietic recovery. Research support: Cariplo Foundation.