Retrospective Review of Invasive Fungal Disease in a Cohort of Patients with Acute Leukemia
Bibliographic record
Abstract
Abstract Abstract 4265 Background: Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients with acute leukemia (AL). Fluconazole has an established role for prophylaxis in the setting of allogeneic hematopoietic stem cell transplant (AHSCT), and possibly in the setting of acute leukemia. More recently, posaconazole has been shown to reduce the incidence of IFD and mortality in AHSCT recipients, and in patients undergoing chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, with increasing use of broader-spectrum antifungal agents, there are concerns regarding breakthrough infections with resistant organisms. Objectives: The first goal of this study is to define the epidemiology of IFD in all patients with acute leukemia, treated at one academic center (The Ottawa Hospital). The second goal is to identify risk factors, which could stratify patients into a very high risk category for the development of IFD. We hope to identify a subset of patients who would benefit from prophylaxis with broader-spectrum antifungal agents. Methods: We performed a retrospective study of adult patients with acute leukemia (including AML, acute lymphoblastic leukemia (ALL), high-grade MDS and blast-phase CML) treated at our institution between May 2009 and April 2011. Patients at all stages of treatment were included. All patients treated with antifungal agents were identified through our pharmacy database. Computerized medical records were reviewed for baseline demographics (age, gender, occupation, diagnosis, days of neutropenia and comorbidities), as well as treatment-related variables (chemotherapy regimen, conditioning regimen, date of AHSCT, response to treatment and presence of GVHD). Imaging, microbiology and biopsy results were also collected. Proven and probable IFD were defined as per the 2008 EORTC/MSG revised criteria. Patient characteristics were compared using Fisher’s exact test. Results: We identified 89 inpatient encounters. Primary diagnosis was AML in 58, high-grade MDS in 15, ALL in 12, blast-phase CML in 3 and PCL in 1 patient. 42 patients were undergoing induction chemotherapy and 10 were undergoing consolidation. 30 patients were post-AHSCT. Contrary to prior studies, all patients were on fluconazole prophylaxis. Out of these 89 encounters, 8 patients (9%) were diagnosed with proven or probable IFD, 12 (13%) met criteria for possible IFD, and the rest (69/89 or 78%) did not meet criteria for IFD. There were 5 probable cases of pulmonary aspergillosis, 1 proven case of hepatic aspergillosis, and 2 proven cases of zygomycosis (1 disseminated and 1 CNS). In terms of risk factors, in our initial analysis, median age was higher in patients with IFD than in patients without (62 vs. 57), though this difference did not reach statistical significance (p = 0.46). There was no difference in the development of IFD based on gender, occupation, days of neutropenia or comorbidities. Although this did not reach statistical significance, almost all patients with IFD had an underlying diagnosis of AML (7/8). In addition, no patients were diagnosed with IFD during consolidation therapy. This is consistent with prior studies. We were not able to assess transplant-related variables, given that only one IFD was diagnosed in a post-AHSCT patient. Overall mortality at 30 days post-admission was significantly higher in the IFD group (6/8 vs. 28/81, p = 0.05). However, only 1 death was directly attributable to the IFD. Otherwise, 3/8 patients with IFD died of refractory leukemia (1 post-AHSCT), 1/8 died of leukemia, 1/8 died of multiorgan failure (not clearly related to IFD), 1/8 survived hepatic aspergillosis and 1/8 survived disseminated mucormycosis. Conclusions: Though limited by sample size, our study indicates that older patients, patients with AML, patients undergoing induction chemotherapy and patients with refractory leukemia may be at highest risk for IFD. In addition, in our cohort, almost all patients with IFD died of their underlying leukemia, while being treated for IFD. It is not clear at this time, but suggestive, that the diagnosis of IFD delayed or interfered with the ongoing treatment plan for some of these patients, possibly contributing to their treatment failure. Therefore, the use of novel antifungal agents would be favored in this group to avoid interruption of leukemia treatment. Further study of this group is currently underway. Disclosures: No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".