The Efficacy Of Umbilical Cord Blood Transplantation With A Low-dose ATG Combined With Intensified Conditioning Regimen In Hematological Malignancies

Objective:In this work,we aimed to evaluate the clinical efficacy and infectious complications after single umbilical cord blood transplantation（UCBT）with a low-dose antithymocyte globulin combined with intensified conditioning regimen in hematological malignancies and explore the effects of infections on clinical outcomes.Methods:We retrospectively reviewed 63 patients who underwent myeloablative UCBT at our institution between July 2013 and April 2019 and analyzed neutrophil engraftment,platelet engraftment,graft-versus-host disease（GVHD）,nonrelapse mortality（NRM）,overall survival（OS）,disease-free survival（DFS）and infectious complications in detail.Infectious complications were divided into groups in accordance with the presence of bacterial bloodstream infection（BSI）and invasive fungal disease（IFD）and the viral load of the cytomegalovirus（CMV）DNA(low:≤10⁵ml^-1,high:>10⁵ml^-1).The differences between groups were compared using the log-rank test and multivariable Cox hazard models.Endpoints were used to identify the effects of infectious complications on NRM,OS and DFS.Results:A total of 63 patients who underwent single myeloablative UCBT（29 with acute myeloid leukemia,28 with acute lymphoblastic leukemia,4 with T-lymphoblastic lymphoma,1 with Ph+mixed phenotype acute leukemia,and 1 with chronic myeloid leukemia[blastic phase]）,were followed up.The median patient age was 24 years（range:1-47 years）,and 31 participants（49.2%）were males.Within 100 days post-transplantation,29 episodes of BSIs were observed in 25 patients at a median time of 3 days（range:0-33days）.Out of these episodes,28 occurred before day 10,and 24（38%）patients developed infections before engraftment.Within 100 days post-transplantation,eight patients（2 with proven IFD,1 with probable IFD,and 5 with possible IFD）were diagnosed with IFD.The median onset of IFD was 17.5 days（range:1-63 days）.A total of 60 patients developed CMV infection at a median time of 61 days（range:22-343 days）from the viral DNA copies that reached the maximum.The CMV DNA viral loads were below 10⁵ml^-1in 24 patients and exceeded 10⁵ml^-1 in 36 patients.The differences in NRM,OS,and DFS between the bacterial and nonbacterial BSI groups and between the IFD and non-IFD groups were not significant.No difference was observed in NRM between the high(viral load>10⁵ml^-1)and the low(viral load≤10⁵ml^-1)CMV viral load groups.The high and the low CMV viral load groups had an OS（P=0.015）of 70.7%and 38.6%,respectively,and DFS（p=0.043）of 66.4%and38.6%,respectively.Multivariate analysis showed that the stage of the primary disease NR（HR=15.672,95%CI:3.476-70.662,P=0.000;HR=11.698,95%CI:3.266-41.890,P=0.000;HR=17.691,95%CI:3.116-100.446,P=0.001）,acute leukemia（HR=14.933,95%CI:1.492-149.480,P=0.021;HR=22.327,95%CI:3.547-140.515,P=0.001;HR=17.691,95%CI:3.116-100.446,P=0.001）,major ABO discrepancy（HR=0.077,95%CI:0.013-0.453,P=0.005;HR=0.090,95%CI:0.021-0.393,P=0.001;HR=0.096,95%CI:0.025-0.374,P=0.001）,and high CMV viral loads（HR=4.804,95%CI:1.025-22.524,P=0.046;HR=6.912,95%CI:1.943-24.590,P=0.003;HR=4.691,95%CI:1.476-14.915,P=0.009）showed negative effects on NRM,OS,and DFS,respectively.The risk factors of high CMV viral loads and their effects on NRM and OS were also identified.In univariate analysis,being female（HR=0.115;95%CI:0.014-0.942;P=0.044）,stage of primary disease NR（HR=7.883;95%CI:1.942-32.003;P=0.004）and acute leukemia（HR=8.730;95%CI:2.121-35.937;P=0.003）were the risk factors associated with poor OS.The stage of primary disease NR（HR=8.372;95%CI:1.681-41.696;P=0.009）and acute leukemia（HR=8.514;95%CI:1.686-42.996;P=0.010）were the risk factors for NRM.Multivariate analysis showed that the stage of primary disease NR（HR=6.478;95%CI:1.232-34.053;P=0.027）and acute leukemia（HR=6.867;95%CI:1.227-38.0853;P=0.028）were the risk factors for NRM,and acute leukemia（HR=5.539;95%CI:1.300-23.594;P=0.021）showed a negative effect on OS.Conclusion:In our experience,UCBT resulted in a delay in hematopoietic recovery but was associated with a low risk of GVHD and improved quality of life.Infections were common after UCBT,and high CMV viral load(viral load>10⁵ml^-1)was a risk factor associated with poor OS.