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%.
Haploidentical SCT with T-cell depleted grafts is a therapeutic option for refractory cytopenias and severe aplastic anemia after nonresponse to immunosuppressive treatment if no HLA-matched donor is available. Recovery of neutrophiles and platelets were fast and TRM was low, even if retransplantation was necessary. Since spontaneous outcome of these conditions are poor, alternative donor SCT is a realistic option for these patients.
No relevant conflicts of interest to declare.
