Risk Factors for Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience

Abstract

Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34(+) cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 10(6) cells/kg increase in CD34(+) cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed.

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years

“…Multiple factors reported to be associated with the risk of IFI include donor type, conditioning regimens, prolonged neutropenia, GVHD, and highdose corticosteroids (Fukuda et al, 2003;Thursky et al, 2004;Ozyilmaz et al, 2010;Omer et al, 2013). According to our data, we found similar risk factors infecting IFI.…”

“…Previously identified risk factors of IFI include donor type, GVHD, high-dose corticosteroids, increased ferritin levels, and so on (Fukuda et al, 2003;Thursky et al, 2004;Ozyilmaz et al, 2010;Omer et al, 2013). Epidemiology and risk factors of IFI differ due to the changes in antifungal prophylaxis and treatment in different regions.…”

Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation

“…Some articles have already suggested that the development of acute GvHD is a risk factor for opportunistic infection, such as invasive fungal disease and CMV reactivation. 15,19,28 Our previous study also suggested that although the incidence of grade 2-4 acute GvHD was similar between haploidentical HSCT and HLA-identical sibling HSCT, the incidence of grade 1-4 acute GvHD was significantly higher after haploidentical HSCT than after HLA-identical sibling HSCT (Po0.0001) that increased the use of immunosuppressive agents after haploidentical HSCT compared with HLA-identical sibling HCST; this course finally led to an increased incidence of infection. 21 Therefore, the cause of mortality for patients who had both GvHD and infection was classified according to the main and direct causes of mortality in this study.…”

“…Our previous studies suggested that compared with HLA-identical sibling HSCT, haploidentical HSCT increased the incidence of invasive fungal disease (7.1% vs 3.3%, P = 0.007), post transplant lymphoproliferative disease (2.3% vs 0.4%, Po0.05) and CMV disease (8.7% vs 0.0%, P = 0.004) [15][16][17] that are usually associated with a higher risk of mortality after transplant. [16][17][18][19] Moreover, our previous study found that the T-cell subset and dendritic cell subgroup counts, especially CD8 + , CD4 + and CD4 + naive T cells, within the first 90 days post transplant were significantly lower in patients receiving haploidentical HSCT than in HLA-identical sibling HSCT (Po0.05). 20 As a result, the early delayed immune reconstitution after haploidentical HSCT probably led to an increased incidence of infection and infection-related mortality post transplant and finally led to a higher incidence of TRM.…”

PCR in Diagnosis of Invasive Aspergillosis: a Meta-Analysis of Diagnostic Performance

“…espite advances in treatment and supportive care, invasive aspergillosis (IA) is associated with significant morbidity and mortality rates, especially among patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients (1,2). Systemic antifungal prophylaxis is widely used in this patient population (3,4), and patients with recurrent or persistent fever and prolonged neutropenia frequently require empirical coverage with antifungal agents (5).…”