Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

Abstract

The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis.

Pulmonary infections in patients with myelodysplastic syndromes receiving frontline azacytidine treatment

“…A pulmonary localization was documented in 17.6% of microbiologically documented infections and in 73% of clinically documented infections. Overall, these findings are in agreement with previous retrospective experiences focused on infections in MDS patients, which reported a rate of severe infections ranging from 20% to 50% of patients and from 13% to 25% of AZA cycles, being lower respiratory tract the most common localization . The wide range of incidence rates reported in the various studies was presumably related to the biases of retrospective analyses and to the inhomogeneous population characteristics.…”

“…It is worth noting that in our experience, 32.5% of PIs documented during the early cycles were considered of fungal origin and a P‐IFD was documented in 5.5% of patients during the early cycles with a significantly higher rate of early cycles complicated by this type of PI compared to late cycles (1.5% vs 0.6% per treatment cycle, P = .001). Previous retrospective studies on the epidemiology of infections in MDS patients under AZA therapy showed a lower than 2% incidence of P‐IFDs per patient treated but confirmed the time distribution of these infections, being mostly diagnosed during the first AZA cycles . Several reasons can be considered to justify the significant difference in the rate of P‐IFDs in our study compared with other series.…”

“…Only episodes of pulmonary infection unrelated to acute leukemia progression were considered showed a lower than 2% incidence of P-IFDs per patient treated but confirmed the time distribution of these infections, being mostly diagnosed during the first AZA cycles. [9][10][11][12][13] Several reasons can be considered to justify the significant difference in the rate of P-IFDs in our study compared with other series. Half of P-IFDs were diagnosed at the level of possible infection essentially based on the radiologic findings showing pulmonary lesions fulfilling the criteria of fungal disease (nodules with or without halo sign and cavitary lesions) and in the absence of microbiologic documentation.…”

“…4,13,14 However, most of studies on infections during AZA treatment reported a rate of severe infections ranging from 20% to 50% of patients and from 13% to 25% of AZA cycles, being lower respiratory tract the most common localization. 6,[9][10][11][12][13][14] The wide range of incidence rates reported in the various studies was presumably related to the biases of retrospective analyses and to the inhomogeneous population characteristics. Moreover, our data confirm the significant higher incidence rate of severe PIs during the first cycles of AZA treatment.…”

“…4,5 Since the first clinical trials of AZA therapy in MDS patients, pulmonary infections (PIs) have represented very common infectious complications, [6][7][8] as confirmed by epidemiologic studies focused on infections in MDS patients. [9][10][11][12][13][14] However, these studies are based on a relatively small number of patients treated in both myelodysplastic and leukemic phase, sometimes already treated with previous intensive chemotherapies. Thus, the incidence, etiology, and impact of PIs in the overall outcome of untreated high-risk MDS are still unclear.…”