Risk factors for invasive fungal infection in 5‐azacytidine treated patients with acute myeloid leukemia and myelodysplastic syndrome

Tey, Amanda; Shaw, Briony; Cardamone, Luke; Shepherd, Sam; Paul, Eldho; Rogers, Ben; Shortt, Jake

doi:10.1111/ejh.13631

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…On the strength of these data, the European Conference on Infections in Leukaemia (ECIL) does not recommend antifungal prophylaxis in patients with low-to-intermediate risk MDS receiving HMAs (AZA or DAC) ( Maertens et al., 2018 ). Due to the scant available data for AML patients who are elderly or have co-existing diseases, HMA regimens are deemed appropriate instead of standard chemotherapy for such patients ( Tey et al., 2021 ). In our study, the choice of antifungal prophylaxis was at the discretion of the treating physician, according to the patient’s clinical condition.…”

Section: Discussionmentioning

confidence: 99%

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia

Wang

Chen

Lin

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundAcute myeloid leukemia (AML) is a form of cancer that is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells of the hematopoietic system. Patients with acute myeloid leukemia (AML) receiving azacitidine (AZA) alone or in combination with venetoclax (VEN-AZA) are at increased risk for invasive fungal infections (IFIs). We compared the incidence and risk of IFI during these treatment regimens in a single Taiwan hospital.Materials and methodsA total of 61 patients with AML received at least one course of AZA in the hematology ward of China Medical University Hospital (Taichung, Taiwan) between September 2012 and June 2020. Thirty-eight patients (62.3%) received AZA monotherapy; 23 (37.7%) received VEN-AZA.ResultsIncidence rates of probable and proven IFI were 18% and 1.6%, respectively, during AZA treatment. One proven case of Fusarium spp. infection was isolated by skin and soft tissue culture. Most (75%) IFI cases occurred during the first cycle of AZA therapy. Half of all IFI cases occurred in patients with prolonged neutropenia. The risk of IFI was significantly higher for the European LeukemiaNet (ELN) nonfavorable-risk group (intermediate- and adverse-risk group) versus the ELN favorable-risk group and for patients with prolonged neutropenia versus those without (P<0.05 for both comparisons). In this study, median OS did not differ significantly between patients with and without IFIs during AZA-containing regimens (14.6 months vs 13.7 months; P=0.59).ConclusionThe incidence of IFI was high in this AML cohort treated with AZA-containing regiments in Taiwan. The majority of IFI cases occurred during the early cycles of AZA (cycles 1–2). Prospective studies are needed to determine the optimal choice of antifungal prophylaxis agent during VEN-AZA therapy for AML.

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Section: Discussionmentioning

confidence: 99%

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia

Wang

Chen

Lin

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Because there was no significant difference between our AML patient cohorts with respect to the percentage of de novo AML or hematological malignancies prior to AML diagnosis, respectively, we did not perform subgroup analysis focusing on this potential factor. [50,51] In contrast, we could demonstrate a high rate of atypical pneumonia including a significantly higher proportion of pulmonary IFD in AML patients following induction chemotherapy. Several factors might contribute to the high incidence of pulmonary IFD in this well-defined cohort of AML patients: 1 st , ANC are extremely low in AML patients undergoing induction chemotherapy; 2 nd , the duration of severe neutropenia (ANC < 500 per µl); 3 rd , the treatment-associated toxicity of conventional chemotherapy.…”

Section: Discussionmentioning

confidence: 66%

Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia

Scholl

Tober

Schnetzke

et al. 2022

Preprint

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Background: Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. Patients and Methods: We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy (n=102) was 61 years (25-76 years). Patients receiving palliative AML treatment (n=118) had a median age of 75 years (53-91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. Results: AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P <0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P =0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P =0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P <0.001) despite only few patients of the palliative treatment group received Aspergillus spp. -directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG < 1 vs. 50 days for ECOG > 2, P <0.001, respectively) in this intent-to-treat analysis. Conclusion: The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients.

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“…Another potential factor for preexisting pneumonia at AML diagnosis might be attributed to an impaired function of innate immunity (e.g., in patients with antecedent MDS). Because there was no significant difference between our AML patient cohorts with respect to the percentage of de novo AML or hematological malignancies prior to AML diagnosis, respectively, we did not perform subgroup analysis focusing on this potential factor (Tey et al 2021;Andréa et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia

Tober

Schnetzke

Fleischmann

et al. 2022

J Cancer Res Clin Oncol

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Background Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections, while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. Patients and methods We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy (n = 102) was 61 years (25–76 years). Patients receiving palliative AML treatment (n = 118) had a median age of 75 years (53–91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. Results AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P < 0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P = 0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P = 0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P < 0.001) despite only few patients of the palliative treatment group received Aspergillus spp.-directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG < 1 vs. 50 days for ECOG > 2, P < 0.001, respectively) in this intent-to-treat analysis. Conclusion The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients.

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Risk factors for invasive fungal infection in 5‐azacytidine treated patients with acute myeloid leukemia and myelodysplastic syndrome

Cited by 7 publications

References 24 publications

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia

Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia

Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia

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