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Reduced intensity conditioning, combined transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells in patients with severe aplastic anemia.

Authors
  • Li, Xiao-Hong
  • Gao, Chun-Ji
  • Da, Wan-Ming
  • Cao, Yong-Bin
  • Wang, Zhi-Hong
  • Xu, Li-Xin
  • Wu, Ya-Mei
  • Liu, Bei
  • Liu, Zhou-Yang
  • Yan, Bei
  • Li, Song-Wei
  • Yang, Xue-Liang
  • Wu, Xiao-Xiong
  • Han, Zhong-Chao
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2014
Volume
9
Issue
3
Identifiers
DOI: 10.1371/journal.pone.0089666
PMID: 24594618
Source
Medline
License
Unknown

Abstract

We examined if transplantation of combined haploidentical hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) affected graft failure and graft-versus-host disease (GVHD) in patients with severe aplastic anemia (SAA). Patients with SAA-I (N = 17) received haploidentical HSCT plus MSC infusion. Stem cell grafts used a combination of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow and G-CSF-mobilized peripheral blood stem cells of haploidentical donors and the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs), respectively. Reduced intensity conditioning consisted of fludarabine (30 mg/m2·d)+cyclosphamide (500 mg/m2·d)+anti-human thymocyte IgG. Transplant recipients also received cyclosporin A, mycophenolatemofetil, and CD25 monoclonal antibody. A total of 16 patients achieved hematopoietic reconstitution. The median mononuclear cell and CD34 count was 9.3×10(8)/kg and 4.5×10(6)/kg. Median time to ANC was >0.5×10(9)/L and PLT count >20×10(9)/L were 12 and 14 days, respectively. Grade III-IV acute GVHD was seen in 23.5% of the cases, while moderate and severe chronic GVHD were seen in 14.2% of the cases. The 3-month and 6-month survival rates for all patients were 88.2% and 76.5%, respectively; mean survival time was 56.5 months. Combined transplantation of haploidentical HSCs and MSCs on SAA without an HLA-identical sibling donor was safe, effectively reduced the incidence of severe GVHD, and improved patient survival.

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