| Part 1 Clinical analysis of refractory cytomegalovirus(CMV) infectionfollowing allogeneic hematopoietic stem cell transplantationObjective: Cytomegalovirus(CMV) infection remains the main cause of viral complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Especially, CMV with gene mutations against antiviral drugs could lead to high mortality rate. The purpose of this study is to explore the risk factors and outcome for CMV infection and CMV clinical resistance to antiviral chemotherapy after allo-HSCT.Methods: We retrospectively analyzed the data from a group of patients undergoing allo-HSCT at the First Affiliated Hospital of Soochow University in China during the period of January 2011 to 31 th July 2014. CMV infection occurred in 282 of 685(41.2%) patients treated with myeloablative conditioning regimen. Among the patients with CMV infection, 84 of 282(29.8%) cases developed clinical refractory CMV infection(RCI), and 37 of 282(13.1%) cases progressed into CMV diseases. We analyzed the risk factors of CMV infection and RCI. Based on CMV infection with or without clinical resistance to antiviral chemotherapy, patients with CMV infection were divided into two groups. And the differences between these two groups were analyzed in the cumulative incidence of CMV disease, non-relapse mortality(NRM) and overall survival(OS).Results: Patients with RCI have a higher cumulative incidence of CMV diseases(26.2% versus 7.6%, P<0.001). Seventy nine of 84 cases(94.0%) developed RCI before 100 days after HSCT(5 cases with pp65 detection only). The copy number of CMV-DNA more than doubled compared to its initial baseline in 42 of 74(56.8%) cases after 2 weeks of antiviral therapy, whereas 32 cases did not have a double increase above baseline. CMV disease developed in 15 of 42(35.7%) and 3 of 32(9.4%)(P=0.011) cases in these two groups. Both univariate and multivariate analysis demonstrated that the risk of CMV infection and RCI increased in patients from HLA-haploidentical donor(Haplo) and matched unrelated donor(URD), or without using peripheral blood(PB) as stem cell source. The multivariate analysis revealed that patients who developed acute graft-versus-host disease(a GVHD) ≥ grade 2 have increased risk of developing CMV infection, whereas RCI occurred more frequently in those with total body irradiation-containing regimens(TBI) and a high dosage methylprednisolone(MP) for a GVHD treatment. The prevalence of RCI is three and six times higher in patients who received MP 1-2mg/kg daily(P=0.024) and ≥2mg/kg daily(P=0.001), with an odds ratio(OR) of 2.74 and 6.03 respectively.Conclusions: High dosage corticosteroids treatment is associated with incidence of RCI during the early phase after allo-HSCT. Once RCI turn up after HSCT, it could lead to high non-relapse mortality rate and poor prognosis.Part 2 Clinical analysis of correlation between cytomegalovirusreactivation and relapse of acute myeloid leukemia after allogeneichematopoietic stem cell transplantationObjective: A considerable number of studies have demonstrated that cytomegalovirus(CMV) reactivation after allogeneic hematopoietic stem cell transplantation(allo-HSCT) could enforce graft-versus leukemia(GVL) effect in acute myeloid leukemia(AML) patients. However, the use of antithymocyte globulin(ATG) as part of graft-versus-host disease(GVHD) prophylaxis may dampen this beneficial effect of CMV replication. The purpose of this study is to investigate whether the ATG or non-ATG containing regimens can all benefit from this GVL effect.Methods: In this context, we retrospectively analyzed the effect of CMV reactivation on relapse, survival and prognosis in a total of 227 AML patients who received a myeloablative(MA) conditioning regimen at a single research center between January 2010 and April 2013.Results: Of 227 patients, 110 cases received non-ATG-containing regimens and 117 cases received ATG-containing regimens. CMV reactivation occurred in 45 patients(41%) among non-ATG regimen group and 73 patients(62%) among ATG regimen group(P=0.001). At a median time to follow-up of 27.5 months, a lower risk of cumulative relapse incidence(OR 0.28, 95% CI 0.10-0.79; P=0.016) and a better overall survival(OS)(OR 0.37, 95% CI 0.18-0.74; P=0.005) associated with CMV reactivation were observed in non-ATG group in multivariate analyses. However, CMV reactivation after transplantation in ATG group did not significantly decrease the cumulative incidence of relapse(OR 1.07, 95% CI 0.55-2.07; P=0.840) or improved OS(OR 0.72, 95% CI 0.42-1.22; P=0.220).Conclusion: In conclusion, our results demonstrate that in AML patients following sibling HSCT, the CMV-induced beneficial effect on relapse occurs only in the MA regimens containing no ATG, although ATG promotes CMV reactivation. |
PDF Full Text Request