Abstract
BackgroundA risk score for invasive mold disease (IMD) in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis.MethodsWe retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008) to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012.ResultsOf the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD) were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of < 6 discriminated patients with low (< 1%) versus higher incidence rates (> 5%) of IMD, with a negative predictive value (NPV) of 0.99, (95% CI 0.98-0.99). During 2009-2012, patients with a calculated risk score at admission of < 6 had significantly lower 90-day incidence rates of IMD compared to patients with scores > 6 (0.9% vs. 10.6%, P <0.001).ConclusionAn objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate “screening-out” of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis.
Highlights
Invasive mold diseases (IMDs) such as aspergillosis, and less commonly mucormycosis and fusariosis are a serious complication of myelosuppressive chemotherapy administered for hematological malignancies [1,2,3]
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) or remission-induction chemotherapy for acute myelogenous leukemia / myelodysplastic syndrome (AML/MDS) are at especially high risk, with 20-fold higher rates of aspergillosis compared to patients with underlying lymphoma or multiple myeloma [4]
When the risk score performance was analyzed in different subgroups of hematological malignancy patients with varying IMD prevalence (1.5% to 10.6%) and rates of anti-mold prophylaxis use (7.2% to 57%), we found that a score of < 6 consistently identified a cohort of patients at low risk for IMD with negative predictive value (NPV) ranging from 0.96-0.99 (Table 5)
Summary
Invasive mold diseases (IMDs) such as aspergillosis, and less commonly mucormycosis and fusariosis are a serious complication of myelosuppressive chemotherapy administered for hematological malignancies [1,2,3]. The development of an IMD risk prediction model in patients with hematological malignancies is complicated by the low overall disease prevalence, infrequently analyzed genetic risk factors related to host innate immunity, and dynamic clinical and environmental variables during their course of treatment [8,9]. A risk score for invasive mold disease (IMD) in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. Conclusion: An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate “screening-out” of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis
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