Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving 440 days who engrafted and were discharged without prior IFD. All patients who received ⩾ 20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age 440 years, ⩾ 1 previous SCT, pre-engraftment neutropenia 415 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P o 0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis

Montesinos

Rodríguez‐Veiga

Boluda

et al. 2015

“…6 Moreover, the increasing number of allo-SCTs from unrelated donors; the use of alternative stem cell sources, such as umbilical cord blood, especially in children with prolonged severe neutropenia; and a higher incidence of acute and chronic GVHD, has led to an increase in IFD cases. 7 The diagnosis of IFD is often difficult, especially in children, because of the controversial value of the tests that are currently available, such as the serum Aspergillus galactomannan Ag (AGA), 8,9 the 1-3 b-D glucan test 10 and fungal PCR studies. 11 Thus, diagnosis of IFD is frequently made when the fungal burden is high, which limits the efficacy of antifungal therapy.…”

Section: Introductionmentioning

confidence: 99%

Voriconazole as primary antifungal prophylaxis in children undergoing allo-SCT

Molina

Serrano

Sánchez‐García

et al. 2011

Invasive fungal disease (IFD) causes significant morbidity and mortality among children undergoing allo-SCT. In this prospective pilot study, we analyze voriconazole as primary antifungal prophylaxis. From October 2004 to July 2010, 56 children o18 years of age were enrolled in this study. Patients received voriconazole doses of 5 mg/ kg per 12 h (n ¼ 23) or 7 mg/kg per 12 h (n ¼ 33), with a limiting dose of 200 mg/12 h, from day À1 to day þ 75 or later in patients with active acute GVHD. Patients were followed up for IFD for 6 months. In this series, 37 (66.1%) patients successfully completed treatment (85.7% during neutropenic period) without empirical or preemptive antifungal therapy, adverse effects or IFD. Nine (16.1%) children needed preemptive (n ¼ 2) or empirical (n ¼ 7) antifungal therapy, and one (1.8%) of them developed a fatal probable IFD during the study period. A total of 10 (17.8%) children developed adverse effects related to voriconazole prophylaxis, leading to definitive withdrawal on median day 26.5 (in 7 patients after granulocytic recovery). The most frequent adverse effect was persistent elevation of hepatic enzymes in seven (12.5%) children. There were no differences between doses of 5 and 7 mg/kg per 12 h. Our results suggest that voriconazole can be safely used as primary antifungal prophylaxis in children undergoing allo-SCT.

“…This is in line with earlier studies and reflects the importance of immune reconstitution in preventing the reactivation of IFI. 5,6,16,[22][23][24] The literature also found the following risk factors: hierarchy of diagnosis (proven and probable versus possible), conditioning regimen, duration of neutropenia, GVHD, organ dysfunction and progression of the underlying diseases. However, we failed to confirm the results of these studies.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT in patients with a history of invasive fungal infection

Zhang

Song

Wang

et al. 2008

Earlier invasive fungal infections (IFI) put recipients of hematopoietic SCT (HSCT) at a high risk of IFI-related mortality. We retrospectively assessed the feasibility of HSCT for patients with a history of IFI and the efficacy of secondary prophylaxis. From January 2001 to December 2007, 49 patients with a history of IFI underwent HSCT and most of them received broadspectrum antifungal agents as secondary prophylaxis. After a median follow-up of 355 days (15-967), nine patients experienced failure of IFI prophylaxis, including three cases of IFI-related death, leading to a 2-year cumulative incidence of 18.4 and 6.1%, respectively. Four risk factors for the failure of prophylaxis were found, namely time interval from the diagnosis of IFI to transplantation, residual diseases before transplantation, infection with CMV and use of corticosteroid for the treatment of GVHD. A similar outcome can be achieved in recipients of Auto-and Auto-HSCT. Despite a higher risk of post-transplant progression, residual features of IFI did not affect the overall outcome of HSCT. In conclusion, a history of IFI and residual features are not contraindications to HSCT and secondary prophylaxis by broad-spectrum antifungal agents can protect patients from relapse or progression of an earlier infection.