Incidence and Outcome of Invasive Fungal Diseases after Allogeneic Stem Cell Transplantation: A Prospective Study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs.

Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties

“…[3][4][5] More recent publications clearly demonstrate the feasibility of allo-HSCT in patients with a history of IA. 1,[6][7][8] In the present study, the Infectious Diseases and Acute Leukemia Working Parties of The European Society for Blood and Marrow Transplantation (EBMT) had the aim to analyze the long-term outcome of patients with acute leukemia undergoing allo-HSCT according to the presence-or absence of pre-existing IA.…”

Orphan drugs for the treatment of aspergillosis: focus on isavuconazole

“…Indeed, IA remains the most common cause of invasive fungal infection in HSCT recipients despite implementation of anti-mold prophylaxis at many transplant centers and is a leading cause of infection-related mortality in HSCT recipients, as well as those with acute leukemia. [9][10][11] Among solid organ transplant recipients, lung transplant patients are particularly at risk for IA. In the Transplant-Associated Infection Surveillance Network, IA accounted for 44% of invasive fungal infections in this population.…”

Voriconazole for prophylaxis of invasive fungal infections after allogeneic hematopoietic stem cell transplantation

“…Based on the findings from several studies, the estimated incidence of proven/ probable (according to revised European Organization for Research and Treatment of Cancer [EORTC] and the Mycoses Study Group [MSG] definitions) [3] IFIs following alloHSCT ranges from 8% to 12% in the first year post-alloHSCT [4,5].…”

“…Over time, Aspergillus species have replaced Candida species as the most common fungal pathogen in recipients of alloHSCT [6]. The estimated incidence of EORTC/MSG proven/probable invasive aspergillosis (IA) is approximately 6-7% in the year following alloHSCT, while invasive candidiasis (IC) accounts for approximately 1-5% of cases [2,4,5]. IA accounts for approximately 60% of IFIs in patients who have received alloHSCT, and IC for approximately 25% [1].…”