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

• Published in: PloS one 2014-03, Vol.9 (3), p.e89666-e89666
• Main 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
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia, Aplastic - therapy; Aplastic anemia; Biology; Care and treatment; Child; Child, Preschool; Female; Graft vs Host Disease - prevention & control; Granulocyte Colony-Stimulating Factor - administration & dosage; Haploinsufficiency; Hematopoietic Stem Cell Transplantation; Humans; Male; Medicine; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Monoclonal antibodies; Severity of Illness Index; Stem cell transplantation; Stem cells; Transplantation Conditioning; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0089666

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.