Abstract
The prevention of chronic graft-versus-host disease (cGVHD) is important for recipients of hematopoietic stem-cell transplantation (HSCT). As one of the etiologies, the relationship between early T-cell recovery and subsequent cGVHD development has been the focus of attention. Recently, letermovir (LTV) was approved for preventing cytomegalovirus (CMV) reactivation in the early transplantation phase. Although CMV affects the immune reconstitution after HSCT, the impacts of LTV to prevent CMV reactivation on early T-cell recovery and cGVHD have not been fully investigated. We aimed to identify early T-cell recovery under LTV at day 30 in 15 and 33 recipients from matched related donors (MRDs) and haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo), respectively. Early increases in the levels of total lymphocytes and HLA-DR+ activated T-cells at day 30 were observed under CMV prophylaxis by LTV only in PTCy-haplo recipients and not in MRD recipients. Moreover, PTCy-haplo recipients with LTV showed a significantly higher incidence of cGVHD, but not acute GVHD. Our observations suggest that an early increase in the levels of HLA-DR+ activated T-cells may be implicated in the development of cGVHD in patients treated with PTCy who received LTV. Further studies are warranted to validate our results and elucidate the detailed mechanisms of our new insights.
Highlights
It has been reported that in vivo T-cell depletion therapy with antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) is associated with the suppression of subsequent development of chronic graft-versus-host disease, suggesting the importance of regulating the early T-cell recovery after hematopoietic stem cell transplantation (HSCT) for the long-term immune tolerance [1, 2]
We aimed to examine the early human leukocyte antigen (HLA)-DR+ activated T-cell recovery in matched related donors (MRDs) and PTCy-haplo transplant recipients treated with LTV for CMV prophylaxis and determine the association of lymphocyte recovery with chronic graft-versus-host disease (cGVHD) development
The cumulative incidence of grade II-IV acute GVHD was not significantly different in patients with LTV and without LTV in both MRD and PTCycohort (Table 1). These data demonstrated that only PTCy-haplo but not MRD transplant recipients subjected to CMV prophylaxis by LTV showed early recovery of total lymphocytes as well as HLA-DR+ activated T-cells
Summary
It has been reported that in vivo T-cell depletion therapy with antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) is associated with the suppression of subsequent development of chronic graft-versus-host disease (cGVHD), suggesting the importance of regulating the early T-cell recovery after hematopoietic stem cell transplantation (HSCT) for the long-term immune tolerance [1, 2]. PTCy-haplo transplant recipients show a high rate of CMV reactivation (about 70%) early after transplantation [5,6,7]. Because LTV has been approved only recently, there is still a paucity of literature on its use for the prevention of lymphocyte recovery caused by CMV reactivation in PTCy-haplo transplant recipients [10]
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