Epidemiology, Management, and Outcome of Invasive Fungal Disease in Patients Undergoing Hematopoietic Stem Cell Transplantation in China: A Multicenter Prospective Observational Study

Abstract

The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy (P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital.

Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation

“…The incidence of invasive fungal infection (IFI) has been reported at 9% after allogeneic HCT; some studies show an increase in fungal infection with matched unrelated donor compared to matched related donor. 14,15,16 . In a study of 1400 patients in China, mortality was over 30% in patients with proven IFI 15 .…”

“…14,15,16 . In a study of 1400 patients in China, mortality was over 30% in patients with proven IFI 15 . Bacterial infections, especially after UCBT, are associated with high mortality.…”

Antifungal therapy in hematopoietic stem cell transplant recipients

“…Girmenia et al7 investigated the epidemiology of IFI in a cohort of 1858 allogeneic HSCT recipients showing that grafts from an unrelated donor or umbilical cord blood were associated in multivariate analysis with a high risk of early IFI occurring before day 40. Similarly, Sun et al8 demonstrated that the cumulative incidence of IFI in autologous HSCT patients, recipients of HLA-matched related, haploidentical, and unrelated HSCT was 3.5%, 4.3%, 13.2% and 12.8% respectively.…”

Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients

“…In particular, pretransplantation DM significantly increased the risk of invasive fungal diseases [20][21][22]. The mechanism is unclear, but increased risk may be due to impaired neutrophil function in patients with DM [23,24].…”