Risk factors for invasive aspergillosis and related mortality in recipients of allogeneic SCT from alternative donors: an analysis of 306 patients

Abstract

Invasive aspergillosis (IA) is a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), particularly from donors other than HLA-identical sibling. All 306 patients who underwent alternative donor HSCT between 01 January 1999 and 31 December 2006 were studied. Late IA was defined as occurring X40 days after HSCT. The median followup was 284 days (range, 1-2709). Donors were matched unrelated (n ¼ 185), mismatched related (n ¼ 69), mismatched unrelated (n ¼ 35) and unrelated cord blood (n ¼ 17). According to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, 2 patients already had IA at HSCT, 23 had early IA and 20 had late IA (IA incidence 15%). Eight patients had proven and 37 probable IA. Multivariate analyses showed that significant predictors of IA were delayed neutrophil engraftment, extensive chronic GVHD (cGVHD), secondary neutropenia and relapse after transplant. Early IA was associated with active malignancy at HSCT, CMV reactivation and delayed lymphocyte engraftment. Late IA was predicted by cGVHD, steroid therapy, secondary neutropenia and relapse after HSCT. IA-related mortality among IA patients was 67% and was influenced by use of antithymocyte globulin, steroids, higher levels of creatinine, and lower levels of IgA and platelets. The outcome of IA depends on the severity of immunodeficiency and the status of the underlying disease.

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

“…For these reasons, our overall 1-year CI of 11% cannot be compared with other studies reporting late or very-late IFD incidence after alloSCT (ranging from 7 to 10%). [3][4][5]11 Concerning the type and timing of IFD, we found that, as in previous studies, Aspergillus spp. was the most frequent isolate and the lungs were the most common site, 18 and that the CI of IFD increased during the first year with a gradual decline of episodes until 5 years after SCT.…”

“…24 Concerning the univariate analysis of prognostic factors, our findings were consistent with other studies showing that corticosteroid dosage, aGVHD, cGVHD and CMV infection could increase the risk of post-engraftment or late IFD. 1,5 In addition, we found that post-engraftment IFD was associated with several risk factors that have been previously related with early or overall IFD, such as older age, delayed neutrophil engraftment, previous SCT, HLA mismatch and non PBSCT. 3,4 Our data suggest that ATG-containing regimens could increase the risk of IFD, which is in line with other studies reporting ex vivo T-cell depletion using Cl of IFD alemtuzumab as a risk factor for IFD.…”

“…However, despite the knowledge of several post-engraftment risk factors associated with late IFD (for example, corticosteroid therapy and GVHD), considered as a guide for risk-adapted antifungal prophylaxis, the usefulness of such prophylaxis beyond the alloSCT engraftment is still controversial. [8][9][10] There are a few studies specifically analyzing the epidemiology and risk factors for IFD after engraftment in alloSCT adult recipients [3][4][5]11 and the potential impact of antifungal prophylaxis in this setting.…”

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

“…[1][2][3][4][5][6][7][8][9][10] Based on prior studies, IFI is estimated to occur in 8-17% of pediatric HSCT patients, with a mortality rate of 35-50%. [1][2][3][4][5][6] Incidence varies in the different post-transplant phases, with peaks both pre-and post-engraftment.…”

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

“…The morbidity and mortality associated with the latter remain high despite recent advances in prevention, diagnosis, and treatment (8,9). Long recognized as critical to host defense against Aspergillus species, particularly when conidia escape macrophage phagocytosis (10), PMNs provide essential anticonidia defense and prevent conidial germination by releasing proteolytic enzymes and rapidly producing ROS in the so-called oxidative burst (11,12).…”