Impact of neutropenia evaluated in terms of the D‐index on invasive fungal disease while on empiric or preemptive antifungal treatment strategy in the early phase after allogeneic hematopoietic stem cell transplantation

Abstract

Background: We retrospectively evaluated the association between the D-index, which reflects both the depth and duration of neutropenia, and proven/probable invasive fungal disease (IFD) early after allogeneic hematopoietic stem cell transplantation (HSCT) at our center (n = 394). Methods: The D-index was defined as the area over the neutrophil curve during neutropenia. The cumulative D-index from the start of neutropenia until the development of infection (c-D-index) was also evaluated as a real-time assessment of neutropenia. Results: There were 19 cases of early proven/probable IFD before and within 1 week after engraftment. Fifteen cases (78.9%) were seen as breakthrough infection while on empiric (n = 7), preemptive (n = 4) or prophylactic (n = 4) antifungal administration with mold-active agents. The c-D-index and lower performance status were identified as independent significant predictive factors for IFD. A receiver operating characteristic (ROC) curve analysis showed that the D-index and c-D-index were more accurate than the simple duration of neutropenia and as accurate as the duration of profound neutropenia for predicting IFD. The sensitivity, specificity, and positive and negative predictive values of the c-D-index using an appropriate cutoff (CO) value (10 644) determined by ROC curve analysis were 73.1%, 63.2%, 9.1%, and 97.9%, respectively. The advantage of the c-D-index to cumulative days of neutropenia in terms of positive and negative predictive values seemed to be small. Conclusions: The appropriate CO value for the c-D-index for predicting IFD was as high as 10 644 in allogeneic HSCT with a more frequent use of empiric antifungal therapy. The c-D-index is useful for assessing the risk of breakthrough IFD.

c-D-index at day 11 can predict febrile neutropenia during chemotherapy in acute myeloid leukemia

“…This finding reminds us that patients with antimicrobial-resistant FN after two or three rotations or additions of antibiotics would be at high risk of IFI. More recently, researchers have specified much more adaptation of the D-indices in IFI therapy [ 12 – 16 ]. In a large cohort study for assessing D-index utility in fungal treatment, proven invasive fungal infection was only seen in 1.01% (4/394) cases even after stem cell transplantation (SCT) [ 12 ].…”

“…More recently, researchers have specified much more adaptation of the D-indices in IFI therapy [ 12 – 16 ]. In a large cohort study for assessing D-index utility in fungal treatment, proven invasive fungal infection was only seen in 1.01% (4/394) cases even after stem cell transplantation (SCT) [ 12 ]. They indicated the adequate cutoff value for c-D-index to predict IFI was 10,644, which is deemed too high.…”

“…The utility of the D-indices has been investigated in some specific clinical situations [ 7 – 11 ]. Recent clinical trials were specifically performed for fungal infections [ 12 – 16 ], and the D-indices were found to be useful in guiding clinical decisions regarding antifungal therapy [ 14 , 16 ].…”

D‐index as a marker of bloodstream infections in patients with allogeneic hematopoietic stem cell transplantation

“…The authors recommended using the D‐index to assess the pretest probability of IMI and to complement positive results of serum galactomannan and β‐ d ‐glucan tests. Since then, the D‐index has been used, with mixed results, to predict invasive fungal infections (IFI) in adult or pediatric patients with AML, 10,24 in patients undergoing HSCT or reduced‐intensity HSCT, 13,14,25 in patients receiving consolidation chemotherapy for AML with high‐dose cytarabine, 9 and in patients receiving induction therapy for acute lymphoblastic leukemia and lymphoma 11 . Of these prior studies, the largest sample size was 68 patients 13 .…”

“…Kimura et al 14 undergoing HSCT or reduced-intensity HSCT, 13,14,25 in patients receiving consolidation chemotherapy for AML with high-dose cytarabine, 9 and in patients receiving induction therapy for acute lymphoblastic leukemia and lymphoma. 11 Of these prior studies, the largest sample size was 68 patients.…”