title: [Clinical observation of mesenchymal stem cell as salvage treatment for refractory acute graft-versus-host disease].
abstract: OBJECTIVE
  To explore the effect of mesenchymal stem cells (MSCs) on refractory acute graft-versus-host disease (GVHD) failed to second-line immunosuppressive therapy.
  
  
  METHODS
  Twenty-two patients with refractory aGVHD received the treatment of first- and/or second-line immunosuppressive agents in combination with MSCs. The MSCs from bone marrow (BM) of HLA-unrelated third-party donors, were used at the median time of 19 (11 - 49) days after aGVHD onset, at a dose of 1×10(6)/kg once with an interval of 14 days. If the symptoms of aGVHD did not improve after continuous infusion four times, MSCs would be discontinued. Meanwhile the proportion of CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)CD25(+) was detected by flow cytometry (FCM) before and 4 weeks after the MSCs infusion.
  
  
  RESULTS
  The median dose of MSC was 4.8 (2.5 - 6.3)×10(6) cell×kg(-1) with a median infusion of 2.5 (1 - 7) times per case. Twelve patients achieved complete response (CR), four partial response (PR) after treatment. The total effective rate was 72.7% (16/22). With a median follow-up of 246.5 (36 - 1116) days post-transplantation, 11 patients survived and 11 died. The causes of death included GVHD(n = 6), infections (n = 3), leukemia relapse (n = 1) and post-transplant lymphoproliferative diseases (n = 1), respectively. The proportion of CD3(+)CD4(+)/CD3(+)CD8(+) was significantly higher at 4th week after MSCs infusion compared to before infusion (1.58 ± 0.54 vs 0.49 ± 0.19, \%t\% = 0.628, P = 0.04). The number of CD4(+)CD25(+) Treg cells had not changed much compared to before infusion (P = 0.606).
  
  
  CONCLUSIONS
  MSCs derived from the BM of a third-party donor are effective to treat aGVHD failed to second-line immunosuppressive therapy after allo-HSCT. MSCs might play a role in aGVHD by regulating the rate of CD3(+)CD4(+)/CD3(+)CD8(+).
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Peng
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Zhou
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Fan
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Xu-tao
authors.initials: XT
authors.lastname: Guo
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Xiang
authors.forename: Qi-fa
authors.initials: QF
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D016879:Salvage Therapy; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents