| Objective: To analysis the efficacy and safety of umbilical cord mesenchymal stem cell(UC-MSC) in children with hematologic malignancy following haploidentical hematopoietic stem cell tranplanation(Haplo-HSCT).Methods: The clinical data of 47 children undergoing Haplo-HSCT were retrospectively analyzed from November 2003 to November 2014, including 25 acute lymphocytic leukemia(ALL), 15 acute nonlymphocytic leukemia(ANLL), 1 chronic myelobalstic leukemia(CML), 2 juvenile myelomonocytic leukemia(JMML), and 4 myelodysplastic syndrome(MDS). 34 patients received UC-MSC from October 2011 to November 2014,and 13 patients without UC-MSC from November 2003 to September 2011. Acute lymphocytic leukemia(AL), MDS, CML patients received conditioning with busulfan,cyclophosphamide plus cytarabine(BU/CY+Ara-C). JMML patients received conditioning with busulfan, cyclophosphamide plus melphalan(BU/CY+Mel).Mycophenolate(MMF), ciclosporin(CSA), methotrexate(MTX), anti-lymphocyte globulin(ATG-F) were used for graft-versus-host disease prophylaxis. All the patients received granulocyte stimulating factor(G-CSF) mobilized bone marrow mixed with peripheral blood hematopoietic stem cell. Survival ananlysis was applied for three-years cumulative overall survival(OS) and disease-free survival(DFS). Univariate analysiswas applied for the overall survival, disease-free survival, transplantation-related mortality(TRM) and relapse rate(RR) of all the patients and overall survival of the patients with UC-MSC.Results:No adverse events were abserved in this study with the administration of UC-MSC. The engraftment rate of patients with UC-MSC was higher than conventional Haplo-HSCT group(100% vs 92.3%).The median neutrophils engraftment time were14 d vs 15 d, and platelet engraftment time were 20 d vs19d, respectively, without significant difference(P>0.05). The three-years cumulative survival(70.6% vs 23.1%,P=0.004), three-years cumulative disease-free survival(52.9% vs 0,P=0), and early cytomegalovirus(CMV) viremia(91.2% vs 38.5%,P=0) in UC-MSC+ Haplo-HSCT group were higher than conventional Haplo-HSCT group with statistical significance.The morbidity of acute graft-versus-host disease(a GVHD)(44.1% vs 92.3%,P=0.003),I-II a GVHD(26.5% vs 61.5%,P=0.041) in UC-MSC+ Haplo-HSCT group was remarkable lower than Haplo-HSCT group with statistical significance, however, the morbidity of III-IV a GVHD(17.6% vs 30.8%), chronic graft-versus-host disease(c GVHD)(26.5% vs 30.8%) 、 hemorrhagic cystitis(HC)(35.3% vs 7.7%) 、pulmonary infection(52.9% vs 46.2%)、relapse rate(32.4% vs 53.8%) had no statistical significance(P>0.05) between the two groups. We came to a conclusion that UC-MSC can increase the overall survival, disease-free survival, and reduce transplantation-related mortality through univariate analysis. CMV viremia(RR=0.327,95%CI 0.126-0.845,P=0.021) can reduce the relapse rate and increase disease-free survival in children post Haplo-HSCT. We found the morbidity of a GVHD and c GVHD, high-risk/relapsed hematologic malignancy, pulmonary infection had no effect on the overall survival through univariate analysis in patients with UC-MSC(P>0.05). Male children(52.6% vs 93.3%,P=0.011) and relapse after transplantation(82.6% vs 45.5%, P=0.026) was the main factor affecting overallsurvival.Conclusion: 1. The application of UC-MSC in children undergoing Haplo-HSCT was safe. UC-MSC can improve the overall survival, disease-free survival and re duce transplantation-related mortality. 2. Male children had a negative impact on overall survival. Early CMV replication can reduce the relapse rate and increase the disease-free survival in children with high-risk/relapsed hematologic malignan cy post Haplo-HSCT. 3.We have found that UC-MSC can reduce the morbidity of a GVHD, but increase the early infection of CMV, without effect on pulmonary infection and relapse in children post Haplo-HSCT. |
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