| Objective:To analyze the clinical characteristics and risk factors of CMV infection in acute leukemia transplant recipients,to explore the predictive value of lymphocyte reconstitution for CMV infection and the effect of CMV infection on post-transplant immune reconstitution,hemorrhagic cystitis and clinical prognosis.Methods:One-hundred and forty-two patients with acute leukemia who underwent allo-HSCT in the Hematology Department of the First Hospital of Jilin University,from June 2011 to June 2018,were retrospectively analyzed.Totally,85 patients were diagnosed as AML and the remaining 57 cases were ALL.Real-time quantitative PCR was performed regularly to monitor CMV DNA load post transplantation.The patients were classified as CMV positive(> 5×102copies/m L)and CMV negative groups(< 5×102copies/m L)based on the CMV DNA level in peripheral blood.Clinical characteristics and risk factors for CMV infection were explored.Meanwhile,the relationship between CMV infection and post-transplantation immune reconstitution,hemorrhagic cysitits,and clinical prognosis was studied.Results:1.the occurrence of CMV infectionOf the 142 AL recipients who received allo-HSCT,82 were occurred with CMV infection after transplantation,and incidence rate was 57.7%(82/142),2 were occurred CMV pneumonia,and incidence rate was 1.4%(2/142).The occurrences of CMV infection were 73.7%(70/95)and 22.0%(9/41)in haplo-identical HSCT recipients and HLA-matched sibling HSCT recipients,respectively(?2 = 31.483,P <0.001).The median time to CMV infection of haplo-identical HSCT recipients was earlier than that of sibling HSCT recipients(35 days vs.48 days)(P = 0.013).Therewas a tendency of longer duration for CMV virusemia in haplo-identical HSCT recipients than that in sibling HSCT recipients(22 days vs.16 days)(P = 0.217).2.analysis of risk factors for CMV infectionUnivariate analysis revealed that using ATG in conditional regimen,a GVHD,on day 14 lymphocyte count after transplantation(LC14)< 0.13×109/L and male recipients were the risk factors for CMV infection.Multivariate analysis suggested that the occurrence of CMV infection was significantly increased in recipients who were used ATG in conditional regimen,occurred a GVHD and on day 14 lymphocyte count after transplantation(LC14)< 0.13×109/L.3.CMV infection and post-transplant immune reconstitutionPercentage and count of CD3+CD4+T in peripheral blood of CMV-positive group were significantly lower than those in CMV-negative group(P = 0.003,P = 0.018),the former percentage of CD3+CD8+ T cells was higher than the latter(P = 0.004),while the CD3+CD8+ T cell counts in the CMV-positive group were higher than the CMV negative group slightly other than in 3 months after transplantation(P = 0.198).The percentage and count of peripheral blood CD19+ B cells in the CMV-positive group were lower than those in the CMV-negative group(P = 0.028,P = 0.039),The percentage and count of CD3-CD56+ NK cells in the CMV-positive group had higher tendency than those in the CMV negative group(P = 0.062,P = 0.090).4.CMV infection and hemorrhagic cystitisThe incidence of hemorrhagic cystitis in the CMV-positive group was 31.7%(26/82),and that in CMV-negative group was 13.3%(8/60),the difference was statistically significant between these two groups(?2 = 6.423,P = 0.011).The incidence of hemorrhagic cystitis in patients with ATG exposure was 32.3%(32/99),and that of control group was 4.7%(2/43),the difference was statistically significant between the two groups(?2 = 12.606,P < 0.001).Multivariate analysis showed that the ATG application was an independent risk factor for hemorrhagic cystitis after transplantation.5.CMV infection and clinical prognosisTo date of 12 March 2019,92 recipients survivied and 50 recipients died,139 recipients who completed hematopoietic reconstitution were included in the survival analysis.The median follow-up time was 20(1 ~ 84)months.The 1-,3-year relapse-free survival rate of the recipients was 74.4%?61.7%,and the overall survival rate was 78.4%,62.9%,respectively.Among them,81 cases were CMV-positive group and 58 cases were CMV-negative group.The NRM of the CMV-positive group and the CMV-negative group after HSCT were 22.2%(18/81)and 15.5%(9/58),respectively(P = 0.556).The relapse rate of CMV-positive and CMV-negative group in AML recipients were 22.9%(11/48)and 31.4%(11/35),respectively(P = 0.386),survival analysis showed that there was no significant difference in the relapse-free survival and overall survival between the CMV-positive group and CMV-negative group after transplantation(P > 0.05).Conclusions:1.The incidence of CMV infection in haplo-identical HSCT recipients was significantly higher than that of sibling HSCT,and the median time of CMV infection in the former was earlier than that in the latter.There was a tendency of longer duration for CMV virusemia in haplo-identical HSCT recipients than that in sibling HSCT recipients.2.Univariate analysis showed that using ATG in conditional regimen,a GVHD,on day 14 lymphocyte count after transplantation(LC14)< 0.13×109/L and male recipients were risk factors for CMV infection after HSCT.Multivariate analysis suggested that using ATG in conditional regimen,a GVHD,on day 14 lymphocyte count after transplantation(LC14)< 0.13×109/L were independent risk factor for CMV infection.3.The level of immune reconstitution after transplantation is closely related to CMV infection.According to the recovery of peripheral blood lymphocyte counts on day +14 after transplantation,it can provide a reference for early identification of high-risk groups with CMV infection.4.CMV infection can delay the post-transplant immune reconstitution,mainly due to delayed immune reconstitution of CD3+CD4+ T cells and CD19+ B cells,whereas CMV infection had a tendency to accelerate the reconstitution of CD3-CD56+NK cells.5.CMV infection increases the risk of hemorrhagic cystitis,but it is not an independent risk factor.6.CMV infection has an increased risk for NRM in AL recipients after transplantation,and has a tendency to reduce recurrence in AML recipients after transplantation,but has no significant effect on long-term survival after transplantation in patients with acute leukemia. |
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