Incidence and Outcomes of Fungal Infections in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Eight Years Single Center Experience

Over the past decade there has been substantial increase in the available antifungal agents for prevention and treatment of fungal infections. In parallel with this change, transplant strategies have become more immunosuppressive and less myelo-suppressive. In light of these two dynamic changes, true current incidence and outcome of fungal infections in patients undergoing HCT remain unknown. To address this, we evaluated incidence and outcome of fungal infections in patients undergoing HCT in a large pediatric transplant center with the focus on reduced intensity conditioning (RIC) transplant, from January 2004-July 2012.

Forty two patients, 30 with non-malignant disease, and 12 with malignant disease were identified to have proven fungal infection and reviewed retrospectively. Donor source was unrelated donor in 35 (83.3%) and matched related in 7 (16.6%). Stem cell source was bone marrow in 31 (73.8%), peripheral blood stem cells in 7 (16.6%) and cord blood in 4 (9.5%). Thirteen (31%) patients received alemtuzumab and 21 (50%) received antithymocyte globulin (ATG) as part of conditioning. Fungal infection was defined as a positive fungal culture in blood or in body fluids or relevant tissue.

In our cohort, highest number of fungal infections was caused by Candida albicans, followed by Candida glabrata and Aspergillus species. Table 1 describes the results in detail. Thirty one (75%) patients had a history of acute (50%) or chronic GVHD (25%) requiring use of additional immunosuppressive therapy.  Infection with mold was uncommon in patients without GVHD. However, there was no difference in distribution of infection with yeast vs molds in deceased patients with h/o GVHD. Overall survival for patients with proven fungal infection was low at 33%. Fungal infection was attributed to be the cause of death in almost half of the deceased patients (13/28 patients - 46%).

In our cohort, the overall incidence of culture proven fungal infection, distribution of different fungal infections, and patient outcomes are similar to previous reports. Patients with h/o GVHD and associated immune suppression appear to be at a higher risk of developing infections with molds compared to patients without GVHD, where yeast remain almost an exclusive offender. 

Table 1. Fungal Infections in pediatric patients undergoing HSCT
Characteristics	Number (range/%)
Total number of patients	42
Age in years	11.33 ( 0.52 -28.67)
Proven fungal infections	57
Median post-HSCT day of fungal detection (range)	91.5 (2-2733)
Type of infection
Fungemia only	15
Yeast	12
Mold	3
Invasive infection with organ involvement	27
Yeast	15
Mold	12
Conditioning regimen
MAC	23 (55%)
RIC	18 (43%)
No conditioning	1 (2%)
Patients with GVHD with fungal infection
Total	31/42 (74%)
Acute GVHD	21 (50%)
Chronic GVHD	10 (25%)
Overall outcome
Alive	14 (33%)
Deceased	28 (67%)
Patients deceased due to fungal infection	13/28 (46%)

MAC – Myeloablative conditioning