How we treat invasive fungal diseases in patients with acute leukemia: the importance of an individualized approach

Abstract

Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with acute leukemia. Because of leukemia’s heterogeneity, the risk for IFDs is highly variable. We therefore apply a risk-adapted antifungal strategy with strong emphasis on pretreatment and day-15 posttreatment to allow earlier and more individualized interventions. We determine pretreatment risks for IFDs based on 4 factors: (1) host fitness for standard therapy (ie, fit, unfit, or frail); (2) leukemia resistance (high vs low probability of achieving complete remission [CR]); (3) anticipated treatment-related toxicity such as neutropenia, mucositis, and steroid-induced immunosuppression; and (4) patient exposure to opportunistic fungi. Accordingly, we stratify patients as high, intermediate, or low risk for IFDs and apply risk-adapted antifungal strategies, including primary or secondary prophylaxis and diagnostic-based preemptive or empiric therapy. Prevention of IFDs also relies on optimizing organ function, decreasing exposure to opportunistic fungi, and improving net state of immunosuppression with use of better-tolerated and investigational agents for unfit patients and those with adverse leukemia biology. Novel targeted and safe therapies that can achieve higher rates of sustained CR among patients with adverse genetics offer the best promise for reducing the burden of IFDs in these patients.

Resultados en el tratamiento de pacientes con leucemia mieloide aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica entre los años 2010-2014: Analysis of 63 patients between 2010-2014

“…Si bien la QT de inducción es altamente efectiva, presenta toxicidades importantes a considerar que pueden influir en la morbimortalidad de nuestros pacientes tales como citopenias, infecciones, hemorragias, síndrome de lisis tumoral, alteraciones hidroelectrolíticas y otras complicaciones [10][11][12][13] . En nuestra serie encontramos una alta incidencia de infecciones fúngicas como causal de la neutropenia febril post quimioterapia de inducción, lo cual fue superior a lo reportado 14 . Como posibles explicaciones a este fenómeno se podría asociar a una selección positiva por uso de profilaxis antimicrobiana y a que la profilaxis antifúngica empleada actualmente no es la adecuada.…”

Tackling antibiotic resistance in febrile neutropenia: current challenges with and recommendations for managing infections with resistant Gram-negative organisms

“…These various factors reflect in many ways the risk factors for any infection in this patient population. Specifically, these risk factors represent a summary of various factors related to the host (net state of immunosuppression, co-morbidities, organ dysfunction and frailty), tumor (in remission or relapse) and intensity of chemotherapy, as well as past and/or current exposure to MDR GNB [56].…”

Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia

“…31 Triggers for ordering chest CT scan in the induction remission phase of the treatment include respiratory signs and symptoms (cough, thoracic pain, runny nose, hoarseness, dyspnea, abnormal respiratory sounds), persistent or recurrent fever in the context of neutropenia, or a positive fungal biomarker, such as serum Aspergillus galactomannan antigen (GMI). 27 No image is typical of a specific diagnosis. Therefore, the correct interpretation of the CT scan must take into consideration the clinical context, including the underlying disease, treatment, timing of occurrence, symptoms, and the results of other tests.…”

“…2 Although invasive aspergillosis (IA) is by far the most frequent invasive fungal disease (IFD) in this context, infection caused by other molds such as Fusarium and the agents of mucormycosis might also occur, and the clinical picture is usually indistinguishable from aspergillosis. 27 Diffuse PI might also occur after treatment for acute leukemia. Viral disease (respiratory viruses), 28 transfusion-related acute lung injury, 29 cardiac dysfunction with pulmonary edema, capillary leak syndrome, diffuse alveolar hemorrhage, cryptogenic organizing pneumonia, and immune reconstitution syndrome are possible etiologies.…”