Alternative Donor Stem Cell Transplantation In Aplastic Anemias and Refractory Cytopenias Is Save and Feasible With T- and B-Cell Depleted Haploidentical Grafts

Allogeneic stem cell transplantation is still the curative treatment option for the majority of patients with severe aplastic anemia and refractory cytopenias. However, a HLA-matched donor is not available for all patients. Alternative donor transplantation has been an experimental treatment option, limited by high rejection rates and transplant related mortality. We performed a prospective clinical trial to evaluate the safety and feasibility of haploidentical stem cell transplantation, since haploidentical family members are always available donors. We investigated a cohort of 10 pediatric patients with severe aplastic anemia or myelodysplatic syndrome transplanted (refractory cytopenia) with T-cell depleted grafts between 2004 and 2011. 7 patients had myelodyslastic syndrome with refractory cytopenia (MDS-RC), 3 had severe aplastic anemias (SAA) refractory to immunosuppresive treatment. 3 patients received a 2nd SCT after rejecting the graft from matched donors. Median age was 11.4 years. Standard conditioning regimen consisted of Fludarabin 3-4x40mg/m², Thiotepa 1-3x5mg/kg, Melphalan 2x70mg/m² (n=8) and serotherapy using OKT3 (n=5) and ATG (n=5). 8 patients received additional total lymphoid irradiation (TLI 7 Gy) to prevent graft rejection. In vitro graft manipulation was carried out by direct depletion using antiCD3/19 magnetic microbeads. A median number of 10.1x10⁶ CD34⁺ progenitor cells and 27x10³ T-cells/kg body weight (BW) were transfused. Pharmacological GvHD prophylaxis (graft vs. host disease) was carried out with Mycofenolate until day 60, if residual T-cells in the graft exceeded 25000/kg BW. Primary engraftment occurred in all patients Median time to reach 500/µl neutrophiles was 9 days (9-11). Independence from platelet substitution was reached after 13 days (8-16). Three patients rejected the graft later on. 6/10 patients had no signs of acute GvHD or GvHD grade I, 2 patients had GvHD grade II. TRM at day +100 and after 1 year was 0% and 20%, respectively. Event free survival (EFS) at 3 years was 80%.