title: Reduced intensity conditioning, combined transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells in patients with severe aplastic anemia.
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.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Chun-Ji
authors.initials: CJ
authors.lastname: Gao
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Wan-Ming
authors.initials: WM
authors.lastname: Da
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Cao
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zhou-Yang
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Song-Wei
authors.initials: SW
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xue-Liang
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Wu
authors.affiliation: TEDA Research Center of Life Science and Technology, State Key Laboratory of Experimental Hematology, Institute of Hematology, Tianjin, China.
authors.forename: Zhong-Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D057895:Haploinsufficiency; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D012720:Severity of Illness Index; D019172:Transplantation Conditioning; D055815:Young Adult
chemical_list: D016179:Granulocyte Colony-Stimulating Factor