Features of Epstein-Barr Virus and Cytomegalovirus Reactivation in Acute Leukemia Patients After Haplo-HCT With Myeloablative ATG-Containing Conditioning Regimen

BackgroundHaploidentical donor hematopoietic cell transplantation (haplo-HCT) has become a preferred option for patients without HLA-matched donors, but it increases the risk of viral reactivations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common viruses post-HCT, but limited data have been reported in the setting of haplo-HCT. MethodsWe conducted a retrospective study enrolling acute leukemia patients who received haplo-HCT with myeloablative conditioning regimen employing ATG in our center from July 2014 to July 2017. All the patients enrolled were EBV-IgM and EBV-DNA negative but EBV-IgG positive, and so were their donors. The same went for CMV as well. ResultsIn total, 602 patients were recruited consisting of 331 with acute myeloid leukemia (AML) and 271 with acute lymphoblastic leukemia (ALL). One-year cumulative incidences of EBV (22.9% +/- 2.4% vs. 27.4% +/- 2.8%, P = 0.169) and CMV (24.7% +/- 2.4% vs. 29.4% +/- 2.8%, P = 0.190) reactivation were comparable between AML and ALL. EBV and CMV were independent risk factors for each other. In the AML group, male recipients [HR = 1.275, 95% CI (1.001-1.624), P = 0.049] and acute graft-versus-host disease [HR = 1.592, 95% CI (1.001-2.533), P = 0.049] were independent risk factors for EBV reactivation and CMV reactivation, respectively. CMV rather than EBV reactivation was related to a trend of worsened treatment-related mortality (TRM) (15.6% +/- 0.1% vs. 10.2% +/- 0.0%, P = 0.067) and progression-free survival (PFS) (60.6% +/- 4.1% vs. 70.3% +/- 2.3%, P = 0.073), while significant impacts were revealed only in the subgroup analysis. CMV reactivation resulted in a remarkable inferior 2-year overall survival (OS) (64.2% +/- 5.7% vs. 77.6% +/- 3.2%, P = 0.038) and PFS (55.0% +/- 5.9% vs. 71.9% +/- 3.4%, P = 0.042) in ALL patients. On the other hand, in the EBV+/CMV- subgroup, relapse was lower in ALL patients (8.2% +/- 0.2% vs. 32.4% +/- 0.8%, P = 0.010) compared with AML patients, which led to a superior 2-year OS (82.0% +/- 6.2% vs. 60.3% +/- 8.8%, P = 0.016) and PFS (74.5% +/- 7.0% vs. 57.5% +/- 8.4%, P = 0.036). ConclusionWe concluded that EBV and CMV reactivations were frequent in acute leukemia patients after haplo-HCT, with possibly distinctive risk factors from HLA-matched HCT. There could be a potential interaction between EBV and CMV, but impacts on transplant outcomes remained complex.

Automated summary

After haploindentical donor hematopoietic cell transplantation, the reactivation rates of EBV and CMV are higher and may have distinctive risk factors compared to HLA-matched HCT. Male recipients and acute graft-versus-host disease are independent risk factors for EBV and CMV reactivation. CMV reactivation is associated with worsened treatment-related mortality and progression-free survival, significantly impacting the survival of ALL patients. In the EBV+/CMV- subgroup, ALL patients have a lower relapse rate and better overall survival and progression-free survival compared to AML patients.