Invasive aspergillosis in patients with acute leukemia: update on morbidity and mortality -SEIFEM-C Report.

Aspergillus species represent the main cause of fungal infections in patients with acute leukemia [1, 2]. During the past few years, we have conducted 2 consecutive multicenter studies to evaluate the incidence of and mortality rate associated with aspergillosis among these patients [2, 3]. In the first study (conducted from 1987 through 1998), among 4448 cases of acute leukemia (both lymphoid and myeloid), we identified 209 cases of proven or probable invasive aspergillosis, with an incidence of 4.7% and an attributable mortality rate (AMR) of 48% [2]. More recently (from 1999 through 2003), among a population of 4185 patients with acute leukemia, 257 proven or probable cases of aspergillosis were diagnosed, with an incidence of 6.1% [3]; the AMR was 38.5% (99 of 257 cases ended in death). Six institutions participated in both studies; an analysis of all patients with acute leukemia from 1987 through 2003 has been possible. An absolute increase in cases of aspergillosis was at FACOLTA' INGEGNERIA NAPOLI - BIBLIOTECA CENTRALE on April 11, 2012 http://cid.oxfordjournals.org/ Downloaded from CORRESPONDENCE • CID 2007:44 (1 June) • 1525 observed, but the incidence rate remained stable. Conversely, a significant reduction in AMR was documented (from 60% [12 of 20 cases ending in death] during 1987– 1988 to 32% [24 of 76 cases ending in death] during 2002–2003; ). P p .019 Since 2003, we have had the perception that the application of a correct and timely diagnostic examination (including, for example, a galactomannan test, PCR, and a high-resolution chest CT scan) and the availability of more efficacious and less toxic antifungal drugs (i.e., voriconazole and caspofungin) have modified the epidemiology of aspergillosis. To confirm this perception, a new study was performed in 2006. Two hundred thirty-seven new cases of acute leukemia were recorded among the 6 centers that participated in the other 2 studies. Invasive aspergillosis was diagnosed in 30 of these cases (6 [20%] were proven cases, and 24 [80%] were probable cases), with an incidence of 12.7%; invasive aspergillosis was the cause of death in only 4 patients (AMR, 13%). A comparison was made between the incidence of and AMR associated with acute leukemia in 2002 (the year before the introduction of caspofungin and voriconazole) and 2006. A significant increase in the incidence (25 of 430 cases vs. 30 of 237 cases; P p .002) and a decrease—although not significant—in the AMR (24% [6 of 25 cases ending in death] vs. 13% [4 of 30 cases ending in death]) were observed. These data confirm recent results showing that a prompt diagnostic examination is very helpful for identification of aspergillosis [4]. The apparent increase in the incidence may have occurred because diagnoses that were only suspected in the past are now more easily affirmed. In particular, the increased incidence of probable aspergillosis that we observed could be related to the increased reliability of galactomannan tests, allowing for a decrease in the proportion of possible aspergillosis, according to the upgraded European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria (5). The absence of common upgraded guidelines for the use of new antifungal drugs had allowed all participating centers to use different therapeutic approaches, according to literature [6–8], local experience [9], and international trials [10]. On the other hand, clinical data on the use of voriconazole, caspofungin, or liposomal amphotericin B revealed no difference with regard to mortality. The lack of statistical difference in AMR was probably because of the low number of cases, although present data confirm a trend of decreased AMR, which was observed in a previous study [3]. In conclusion, our data suggest that, presently, mortality attributable to invasive aspergillosis associated with acute leukemia is probably a less compelling problem than is morbidity. New antifungal drugs are associated with decreased mortality rates, although they are also associated with higher costs. An effective prophylaxis could play a role in decreasing the number of cases of aspergillosis. Recent data have revealed that posaconazole prophylaxis might decrease the incidence of aspergillosis [11], whereas, in the past, fluconazole or itraconazole failed to do this.