ABSTRACT
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 8-10/10 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 × 10(5) CD3(+) /kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II-IV 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 II-IV aGVHD, early transplantation-related mortality, and extensive cGVHD.
Subject(s)
Antigens, CD34 , Graft vs Host Disease/prevention & control , Lymphocyte Depletion , Lymphocyte Transfusion , Peripheral Blood Stem Cell Transplantation , Unrelated Donors , Adolescent , Adult , Child , Disease-Free Survival , Female , Graft vs Host Disease/mortality , Histocompatibility Testing , Humans , Male , Neoplasms/mortality , Neoplasms/therapy , Prospective Studies , Survival RateABSTRACT
The amount of acid citrate dextrose formula A (ACD-A), which is a commonly used anticoagulant in leukopheresis, has to ensure both the safety of the donor and guarantee the integrity of the peripheral blood stem cell (PBSC) product until its transplant. Two recent consecutive cases of postthaw PBSC product clotting initiated a look-back investigation of the ACD-A percentage in leukopheresis products collected in our facility. The data indicated a significant difference between the average amount of ACD-A in prefreezing products collected during 2006 (11.4%) and in products collected during 2007 and 2008 (8.8% and 8.7%, respectively). These findings and the fact that the two clotted products had less than 7% ACD-A indicated that insufficient amount of anticoagulant might contribute to their clotting. This investigation prompted us to modify our collection and thawing procedures to prevent similar events in the future.