Invasive Mold Infections in Allogeneic Hematopoietic Cell Transplant Recipients in 2020: Have We Made Enough Progress?

Abstract

Background: Despite progress in diagnostic, prevention, and treatment strategies, invasive mold infections (IMIs) remain the leading cause of mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients.

Methods: We describe the incidence, risk factors, and mortality of allo-HCT recipients with proven/probable IMI in a retrospective single-center 10-year (01/01/2010-01/01/2020) cohort study.

Results: Among 515 allo-HCT recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%), and other molds (8/51, 15%). Overall, 35/51 (68.6%) breakthrough IMIs (bIMIs) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included prior allo-HCT (sub hazard ratio [SHR], 4.06; P = .004) and grade ≥2 acute graft-vs-host disease (aGvHD; SHR, 3.52; P < .001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (P = .02). Mortality predictors included disease relapse (hazard ratio [HR], 7.47; P < .001), aGvHD (HR, 1.51; P = .001), CMV serology-positive recipients (HR, 1.47; P = .03), and IMI (HR, 3.94; P < .001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (log-rank P = .47). At 1 year post-IMI diagnosis, 70.8% (34/48) of the patients were dead.

Conclusions: IA mortality has remained relatively unchanged during the last 2 decades. More than two-thirds of allo-HCT recipients with IMI die by 1 year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

Keywords: allogeneic hematopoietic cell transplant recipients; epidemiology; invasive aspergillosis; invasive mold infections; mortality.

Figure 1.

A, Cumulative incidence of proven or probable invasive mold infection (IMI), invasive aspergillosis (IA), and non-IA IMI during the first year after an allogeneic hematopoietic cell transplant (HCT). B, Cumulative incidence of proven or probable IMI during the first year after an allogeneic HCT based on whether patients had a prior allogeneic HCT. For 3 patients with >1 IMI, incidence was assessed based on non-IA IMI.

Figure 2.

Absolute numbers of allogeneic hematopoietic cell transplant (HCT) performed during the study period and invasive mold infections (IMIs), with proportions of antifungal prophylaxis administered at the time of HCT, presented by calendar year. Only primary antifungal prophylaxis prescribed at the time of HCT was considered in this figure, without taking into consideration subsequent changes on antifungal prophylaxis performed during the patient’s post-HCT course.

Figure 3.

All-cause mortality presented as Kaplan-Meier survival curves for allogeneic hematopoietic cell transplant (HCT) recipients based on the (i) type of IMI: proven or probable invasive aspergillosis (IA) vs other-than-Aspergillus invasive mold infection (IMI) by (A) 84 days and (B) 1 year after IMI diagnosis; (ii) timing of IMI diagnosis: very early (0–30 days), early (31–180 days), and late (>180 days) post-HCT by (C) 84 days and (D) 1 year after IMI diagnosis; (iii) surgical intervention or not for patients with a proven or probable non-IA IMI by (E) 84 days and (F) 1 year after IMI diagnosis.