Work

NiCord® Expanded Hematopoietic Progenitor Cells (HPC) Are Capable of Prolonged Myeloid and Lymphoid Engraftment Following Myeloablative Dual Umbilical Cord Blood (UCB) Transplantation

Year: 2012

Type: article

Abstract: Human transplantation of expanded HPCs resulting in durable, robust donor myeloid and T-cell engraftment has yet to be reported. We report here preliminary results of a pilot study of myeloablative dual UCB transplantation where one UCB unit is expanded ex vivo using the NiCord technology. The NiCord UCB graft consists of an expanded AC133+ and a re-frozen unexpanded AC133- fraction. HPCs were expanded for 21 days in media containing hematopoietic cytokines supplemented with nicotinamide (NAM), a vitamin B3 derivative that delays differentiation and improves engraftment efficiency of human HPCs. Patients were conditioned with total body irradiation (1350cGy) and fludarabine 160mg/m2. Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. Four patients (median age 46; range 41-61) with AML (n = 2) or MDS (n = 2) received a NiCord-containing dual UCB graft. The unmanipulated unit was HLA 4/6 (n = 3) or 5/6 (n = 1) matched with the patient and contained a median cryopreserved TNC dose of 3 x 107/kg. The expanded unit was 4/6 matched (n = 2) or 5/6 HLA-matched (n = 2) with the patient and contained a median cryopreserved TNC dose of 2.3 x 107/kg. After expansion of the AC133+ cell fraction, the TNC and CD34+ cell dose increased a median 455 fold (range 321-577 fold) and 75 fold (range 46-100 fold), respectively. Patients received the NiCord unit that contained a median TNC and CD34+ cell dose of 3.1 x 107/kg (range 1.8-4.3) and 4.6 x 106/kg, respectively. The transplanted negative fraction contained a median of 1.8 x 105 (range 0.8-2.8) CD3+ T-cells/kg. All patients are durably engrafted, with a median time to ANC>500 of 13 days (range 11-18) and platelets >20,000 of 32 days (range 30-36). Peripheral blood CD3+ and CD15+ cell chimerism from the 4 patients at the time of last follow-up are reported. Patient 1, day +280; CD3 (NiCord-2%, unmanipulated-80%, host-18%), CD15 (NiCord-64%, unmanipulated-36%). Patient 2, day +180; CD3 (NiCord-100%), CD15 (NiCord-100%). Patient 3, day +60; CD3 (NiCord-93%, host-7%), CD15 (NiCord-98%, host-2%) Patient 4, day +60; CD3 (unmanipulated-100%), CD15 (unmanipulated-100%). There were no infusion-related or unexpected adverse events and all patients are alive and well without GVHD. These data demonstrate prompt and prolonged engraftment of both myeloid and lymphoid cells derived from expanded HPCs (NiCord) in 3 of 4 patients treated to date. Longer follow-up is required to confirm durability.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2011.12.319