T cell depletion utilizing CD34+ stem cell selection and CD3+ addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients

CD34-selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft-versus-host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post-transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34-selected 810/10 human leucocyte antigen (HLA)-matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n=13) or non-malignant (n=6) diseases. T cells were added back to achieve total dose 1.0-2.5 similar to x similar to 10(5)similar to CD3+/kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade IIIV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15.8%, 23.3%, and 0%, respectively. One patient developed PTLD. One-year infection-related mortality was 5.6%. T cell immune reconstitution was delayed. One-year overall survival was 82.3%. Five patients with malignant disease ultimately died from progressive disease. CD34-selected MUD PBSCT using a defined dose of T cell add-back resulted in high rates of engraftment and low risk of grade IIIV aGVHD, early transplantation-related mortality, and extensive cGVHD.