Infections after Allogeneic Hematopoietic Stem Cell Transplantation with a Nonmyeloablative Conditioning Regimen.
Authors: Frère Pascale , Baron Frédéric , Bonnet Christoffe , Hafraoui Kaoutar , Pereira Maguy , Willems Evelyne , Fillet Georges , Beguin Yves 
Published: October 2019

Abstract
Hematopoietic stem cell transplantation with a non-myeloablative conditioning (NMSCT) could theoretically be associated with a reduced risk of infection because it causes less mucosal damage or severe neutropenia compared to standard myeloablative allogeneic transplantation. Previous studies have sometimes indicated a reduced incidence of infection after NMSCT but other reports have not. We analyzed the incidence and risk factors (Cox model) of infection in 62 patients (16 F and 46 M, aged 54±11 yrs) undergoing NMSCT with a conditioning regimen of low-dose TBI±fludarabine and immunosuppression with CsA+MMF (Seattle protocol). We compared them to 119 recipients (72 peripheral blood (PBSCT) and 47 bone marrow (BMT) transplants) of a conventional HCT. The proportion of NMSCT patients with repeated infections (at least 1, 2, 3 or 4 infections) was significantly lower than in the 2 other groups, but the difference was confined to the first 30 days post-transplant (34% vs 89% and 74%, p<0.001). In NMSCT recipients, donor other than sibling (p<0.0001), older age (p=0.0024), a diagnosis of MDS (p=0.0123), early disease (p=0.0233) and male gender (p=0.0441) were significant risk factors. The incidence of bacteremia was lower (55% vs 70% and 66% at 1 yr, p=0.0264), but the total number of bacteremic episodes (0.9, 1.2 and 1.0 per patient) did not differ in the NMSCT compared to the PBSCT and BMT groups. However, in the first 30 days post-transplant, 4–6 times fewer episodes were encountered in the NMSCT group (p<0.0001). In the NMSCT group, donor other than sibling (p<0.0001), older age (p=0.0126), a diagnosis of leukemia (p=0.0099) and conditioning without fludarabine (p=0.0022), but not neutropenia, were significant risk factors. The incidence of infections other than bacteremia was quite comparable in the 3 groups, but with a significant delay in the NMSCT group (p=0.0002) in which only corticosteroid usage was associated with an increased risk (p=0.0066). The vast majority of infections were bacterial (less frequent in the NMSCT group in the first 30 days), but the rates of fungal or VZV infections were similar in the 3 groups. No case of CMV reactivation or disease occurred among the low risk (donor and recipient seronegative), very few in the intermediate risk (donor alone seropositive), but many in the high risk category (recipient seropositive) and similarly so in the 3 groups. Among NMSCT patients, the risk of CMV infection increased with high risk category (p<0.0001), older age (p=0.0002), donor other than sibling (p=0.0003) and a diagnosis of lymphoma (p=0.0035). Infection was the primary cause of death in 10% or less of the patients, but it contributed to death in 24%, 41% and 27% of the NMSCT, PBSCT and BMT patients, respectively (NS). We conclude that the risk of infection after NMSCT is significantly smaller than after standard allogeneic transplants within 30 days posttransplant, but very similar thereafter.