Curative effect of human umbilical cord mesenchymal stem cells treatment on refractory acute graft versus host disease of children after allogeneic hematopoietic stem cell transplantation

Abstract

Objective To investigate the curative effect and safety of human umbilical cord mesenchymal stem cells (UCMSCs) on the treatment of refractory acute graft versus host disease (aGVHD) of children after allogeneic hematopoietic stem cell transplantation. Methods Five children with refructory aGVHD who hospitalized at the Department of Pediatrics, the Navy General Hospital were treated with UCMSCs retrospectively.Among them, 1 case was male and 4 cases were female, who aged from 18 months old to 15 years old.Two cases had aplastic anemia(AA), 1 case with acute myeloblastic leukemia(AML-M2-CR2), 1 case with acute lymphoblastic leukemia(ALL-CR1) and 1 case with myelodysplastic syndrome(MDS). Three cases received peripheral blood stem cell transplantation from HLA-matched sibling donor, 1 case received mother′s peripheral blood and bone marrow stem cell transplantation from the haploid donor, and 1 case received father′s peripheral blood and bone marrow stem cell transplantation from the haploid donor(both 3/6 HLA locus matched). Prophylaxis for graft versus host disease(GVHD) was performed by using ciclosporin A and methotrexate in 1 case, others used anti-thymocyte globulin, ciclosporin A, mycophenolate mofetil and methotrexate for GVHD prophylaxis.All children developed refractory aGVHD, and they received 3-5 kinds of immunosuppressive agents to treat the refractory aGVHD, but the therapeutic effect was very poor.Then the children received UCMSCs infusion 2 or 3 times(once a week), the UCMSCs dose given was (1.5-2.0)×106 per kg body weight, the curative effect and adverse reactions were apparent after infusion. Results All the children with refractory aGVHD were improved after treatment, the overall response was 100%, and 2 cases were healed and discharged, 1 case suffered from relapsed of aGVHD and died, and the other 2 cases suffered from relapsed of aGVHD and died of thrombotic microvascular disease.On adverse reaction was monitored during infusion, and 2 cases had disease-free survival during 2 years follow-up, without tumour and primary disease recurrence. Conclusions UCMSCs is safe and effective for treatment of refractory aGVHD.In order to improve the curative effect and disease-free survival, the UCMSCs should be reduced early, which can reduce the application and side effects of the immunosuppressor. Key words: Graft versus host disease; Hematopoietic stem cell transplantation; Mesenchymal stem cells; Child