Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies.
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer (NK)-cells during the first 4 months post-transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.
Chen
Xiaohua
X
Division of Bone Marrow Transplantation, St Jude Children's Research Hospital, Memphis, TN, USA.
Hale
Gregory A
GA
Barfield
Raymond
R
Benaim
Ely
E
Leung
Wing H
WH
Knowles
James
J
Horwitz
Edwin M
EM
Woodard
Paul
P
Kasow
Kimberly
K
Yusuf
Usman
U
Behm
Frederick G
FG
Hayden
Randall T
RT
Shurtleff
Sheila A
SA
Turner
Victoria
V
Srivastava
Deo Kumar
DK
Handgretinger
Rupert
R
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology / Q000517:prevention & control; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta