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 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.
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mark B
MB
Geyer
Angela M
AM
Ricci
Judith S
JS
Jacobson
Robbie
R
Majzner
Deirdre
D
Duffy
Carmella
C
Van de Ven
Janet
J
Ayello
Monica
M
Bhatia
James H
JH
Garvin
Diane
D
George
Prakash
P
Satwani
Lauren
L
Harrison
Erin
E
Morris
Mildred
M
Semidei-Pomales
Joseph
J
Schwartz
Bachir
B
Alobeid
Lee Ann
LA
Baxter-Lowe
Mitchell S
MS
Cairo
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D015996:Survival Rate; D061349:Unrelated Donors
D018952:Antigens, CD34