Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

Abstract

In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (

Hematopoietic SCT in patients with a history of invasive fungal infection

“…Earlier studies reported that residual radiological abnormalities before transplantation were a major risk factor for the failure of IFI prophylaxis, [4][5][6]16 which was confirmed by our study. A total of 24 cases (49.0%) in our study had residual disease before transplantation and we assessed the outcome of the preceding IFI in this subgroup.…”

“…No significant difference was found between the two groups regarding distribution of risk factors. The results indicate that Allo-HSCT is feasible for patients with a history of IFI and a favorable outcome can be achieved with powerful prophylaxis 4,6,16 (Figure 2).…”

“…The results of this study indicate that HSCT is feasible for patients with residual infections and a similar outcome can be achieved in patients with and without residual disease through effective prophylaxis. 8,16 Previous studies 16,20,21 showed that risk stratification could effectively identify those who are prone to relapse. We found the following risk factors for failure of secondary prophylaxis (Table 2), namely residual disease before transplantation and shorter time interval from diagnosis to conditioning increased the danger of failure of secondary prophylaxis.…”

“…2 The delayed immune reconstitution after Allo-HSCT put patients at a risk of reactivation of preceding IFI. 4,6,7,16 Therefore, we analyzed the outcome of IFI in the 29 patients receiving Allo-HSCT. In comparison with Auto-HSCT, there was no significant difference in the incidence of the failure of prophylaxis (24.1 versus 10% at 2 years, P ¼ 0.17), IFI-related mortality rate (6.9 versus 5% at 2 years, P ¼ 0.71) and OS rate (54.6 versus 73.6% at 2 years, P ¼ 0.18).…”

“…Appearance of new lesions and an increase in established lesions of more than 20% were considered to be progressive disease (PD), while patients failing to meet either PR or PD were documented as having stable disease (SD). 16,17 Residual disease before transplantation was defined as PR, SD or progressive disease before transplantation. Relapse was defined as the recurrence of fungal lesions in the historical foci in imaging.…”