Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

Abstract

Post-transplant cyclophosphamide (PTCy) has become a promising option after allo-SCT, but infections may be more common than in traditional protocols. We herein report 117 consecutive adults who received PTCy-based alloSCT in our hospital: HaploSCT (34%), MRD (19%), and VUD (47%), respectively. The 18-month incidence of severe bacterial, viral, and IFI was 56%, 69%, and 8.7%, without differences between donor type, except for CMV infection and viral hemorrhagic cystitis, which had a higher incidence in the haploSCT cohort (58% vs. 43% and 30% vs. 8% on day +90, p < 0.05). Late infections by conventional respiratory viruses were common in all groups [33/87 (38%)]. The 2-year survival was 72% and did not differ by donor type. IRM at day 30, day 100, and 18 months was 1.7%, 4.4%, and 12%, without differences by donor type (p = 0.7). The primary cause of IRM was bacterial infection (42%). Grade 2-4 acute GvHD was the only independent predictor of IRM. Donor type had no impact on IRM or on survival. In our study, severe infections were common in all donor types using PTCy, with higher rates of early post-engraftment CMV-I and viral HC in haploSCT recipients, although lethal infections were uncommon and similar in all donor types.

Letermovir Prophylaxis and Cytomegalovirus Reactivation in Adult Hematopoietic Cell Transplant Recipients with and without Acute Graft Versus Host Disease

“…Changes in clinical practice during this study period included the decreased use of ATG and T-cell depleted graft and increased use of post-transplant cyclophosphamide for GVHD prophylaxis. Post-transplant cyclophosphamide has been shown to increase the incidence of CMV infection in CMV-seropositive recipients and was more commonly used in our letermovir group [ 23 , 24 , 25 ]. ATG has also been shown to be associated with increased risk of CMV reactivation, but it is important to consider that many of these trials including ATG were conducted before letermovir was used to prevent CMV infection [ 26 , 27 , 28 ].…”

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Anti-Thymocyte Globulin (ATG) Administration Schedules in Allogeneic Stem Cell Transplantation

“…These include an alteration of the Treg-Tcon ratio, delayed T cell recovery kinetics and selective depletion of alloreactive T cell clones 26 . Infections following PT-CY are common, albeit, non-lethal 27 . ATG when compared with PT-CY retrospectively yields equivalent outcomes in MUD recipients 28 .…”

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

“…Moreover, the CMV DNA peak load was remarkably higher in haploSCT recipients, but the mortality by days 180 and 365 did not differ among comparison groups (55). Garcıá-Cadenas Irene et al studied the impact of HLA donor matching on infection in patients receiving PTCy-based alloSCT (59). They found that haploSCT recipients had a higher incidence of CMV infection/ reactivation at 18 months than other transplant modalities [(61% (95% CI: 41-74%) vs. 44% (95% CI: 31-54%)], whereas lethal infections were uncommon across all these groups.…”