Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in adenosine-deaminase severe combined immunodeficiency

被引：17

作者：

Cancrini, Caterina ^{[3
,4
]}

Ferrua, Francesca ^{[1
,2
,6
]}

Scarselli, Alessia ^{[3
,4
]}

Brigida, Immacolata ^{[1
,2
,3
,4
]}

Romiti, Maria Luisa ^{[3
,4
]}

Barera, Graziano ^{[5
]}

Finocchi, Andrea ^{[3
,4
]}

Roncarolo, Maria Grazia ^{[1
,2
,6
]}

Caniglia, Maurizio ^{[7
]}

Aiuti, Alessandro ^{[1
,2
,3
,4
]}

机构：

[1] Ist Sci HS Raffaele, San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy

[2] Ist Sci HS Raffaele, Pediat Immunohematol & Bone Marrow Transplant Uni, I-20132 Milan, Italy

[3] Childrens Hosp Bambino Gesu, Dept Pediat, Rome, Italy

[4] Univ Roma Tor Vergata, Sch Med, Rome, Italy

[5] Ist Sci HS Raffaele, Pediat & Neonatol Unit, I-20132 Milan, Italy

[6] Univ Vita Salute San Raffaele, Milan, Italy

[7] Childrens Hosp Bambino Gesu, MITA, Rome, Italy

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2010年 / 95卷 / 10期

关键词：

primary immunodeficiency; bone marrow transplantation; reduced intensity conditioning; GENE-THERAPY; SINGLE-CENTER; DEFICIENCY; CHIMERISM; CHILDREN; DISEASE; ADA;

D O I：

10.3324/haematol.2010.025098

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 nave 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.

引用

页码：1778 / 1782

页数：5

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