학술논문
T cell depletion utilizing CD34+ stem cell selection and CD3+ addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients
Document Type
Academic Journal
Author
Geyer, Mark B.; Ricci, Angela M.; Jacobson, Judith S.; Majzner, Robbie; Duffy, Deirdre; Van de Ven, Carmella; Ayello, Janet; Bhatia, Monica; Garvin, James H., Jr; George, Diane; Satwani, Prakash; Harrison, Lauren; Morris, Erin; Semidei-Pomales, Mildred; Schwartz, Joseph; Alobeid, Bachir; Baxter-Lowe, Lee Ann; Cairo, Mitchell S.
Source
British Journal of Haematology. Apr 01, 2012 157(2):205-219
Subject
Language
English
ISSN
0007-1048
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 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.