Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID.
The treatment of choice for severe combined immunodeficiency is bone marrow transplantation from an HLA-identical donor sibling without conditioning. However, this may result in low donor stem cell chimerism, leading to reduced long-term immune reconstitution. We compared engraftment, metabolic, and T-cell and B-cell immune reconstitution of HLA-identical sibling bone marrow transplantation performed in 2 severe combined immunodeficiency infants with adenosine deaminase deficiency from the same family treated with or without a reduced intensity conditioning regimen (busulfan/fludarabine). Only the patient who received conditioning showed a stable mixed chimerism in all lineages, including bone marrow myeloid and B cells. The use of conditioning resulted in higher thymus-derived naïve T cells and T-cell receptor excision circles, normalization of the T-cell repertoire, and faster and complete B-cell and metabolic reconstitution. These results suggest the utility of exploring the use of reduced intensity conditioning in bone marrow transplantation from HLA-identical donor in severe combined immunodeficiency to improve long-term immune reconstitution.
Cancrini
Caterina
C
HSR-TIGET, Istituto Scientifico HS Raffaele, via Olgettina 58, Milan, Italy.
Ferrua
Francesca
F
Scarselli
Alessia
A
Brigida
Immacolata
I
Romiti
Maria Luisa
ML
Barera
Graziano
G
Finocchi
Andrea
A
Roncarolo
Maria Grazia
MG
Caniglia
Maurizio
M
Aiuti
Alessandro
A
D000243:Adenosine Deaminase / Q000172:deficiency; D000361:Agammaglobulinemia / Q000628:therapy; D001402:B-Lymphocytes / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007223:Infant; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D035781:Siblings; D013601:T-Lymphocytes / Q000166:cytology; D019172:Transplantation Conditioning / Q000379:methods*; D014185:Transplantation, Isogeneic
D000243:Adenosine Deaminase
J Pediatr. 2001 Jul;139(1):44-50
11445793
Blood. 2000 Jan 1;95(1):352-9
10607724
Bone Marrow Transplant. 2008 Jan;41(2):119-26
17968328
Science. 2002 Jun 28;296(5577):2410-3
12089448
Blood. 2007 May 15;109(10):4575-81
17272510
Immunol Res. 2009;44(1-3):150-9
19224139
Blood. 2009 Oct 22;114(17):3524-32
19638621
J Immunol. 2003 Mar 1;170(5):2711-8
12594301
Blood. 1999 Oct 15;94(8):2923-30
10515898
Lancet. 2009 Sep 12;374(9693):912-20
19729196
J Pediatr. 1997 Mar;130(3):388-93
9063413
Blood. 1998 Feb 1;91(3):756-63
9446633
J Pediatr Hematol Oncol. 2006 Jul;28(7):403-11
16825984
N Engl J Med. 2009 Jan 29;360(5):447-58
19179314
Blood. 2009 Apr 23;113(17):4114-24
19168787
J Allergy Clin Immunol. 2003 Nov;112(5):973-80
14610491
J Allergy Clin Immunol. 2009 Nov;124(5):1062-9.e1-4
19895994
Immunol Allergy Clin North Am. 2010 Feb;30(1):103-24
20113889
Blood. 2007 Apr 15;109(8):3595-602
17185467
Blood. 2009 Oct 8;114(15):3216-26
19633200
Blood. 2000 Jul 15;96(2):754-62
10887145
Mol Ther. 2006 Oct;14(4):505-13
16905365
Semin Hematol. 1998 Oct;35(4):291-8
9801258