Impact of cytomegalovirus immunodominant HLA‐I donor–recipient matching on the incidence and features of virus DNAemia and virus‐specific T‐cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation

Abstract

AbstractBackgroundWe investigated whether donor‐recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)‐I alleles may impact on the degree of CMV pp65/immediate‐early 1 (IE‐1) T‐cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high‐dose posttransplant cyclophosphamide (PT/Cy‐haplo).MethodsMulticenter observational study including 106 consecutive adult PT/Cy‐haplo patients (34 CMV ID HLA‐I matched and 72 mismatched). A real‐time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV‐specific (pp65/IE‐1) interferon (IFN)‐γ‐producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation.ResultsThe cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs‐CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA‐I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV‐specific IFN‐γ‐producing T‐cell responses (either CD8+ or CD4+) was similar across groups; nevertheless, significantly higher CMV‐specific CD8+ T‐cell counts were enumerated in the CMV ID HLA‐I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation.ConclusionCMV ID HLA‐I matching may impact on the magnitude of CMV‐pp65/IE‐1‐specific CD8+ T‐cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs‐CMVi. image