Fungal infections in patients with acute leukemia

 Corresponding author: Abhishek M. Waghmare Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Fungal infections in patients with acute leukemia Abhishek M. Waghmare 1, *, Neha L. Zod 2 and Harigopal S. Sawarkar 3 1 B–Pharm final year Dr. Rajendra Gode College of Pharmacy, Amravati -444602, Maharashtra (India). 2 Department of Pharmacology, Dr. Rajendra Gode College of Pharmacy, Amravati -444602, Maharashtra (India). 3 Department of Pharmaceutical Chemistry, Dr. Rajendra Gode College of Pharmacy, Amravati444602, Maharashtra (India). World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 Publication history: Received on 06 October 2025; revised on 11 November 2025; accepted on 14 November 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.24.2.1011 Abstract Patients with acute leukemia often undergo intensive chemotherapy, which leaves them highly vulnerable to serious fungal infections. This review looks at patterns of such infections, with a focus on Candida and Aspergillus species, which are the most common culprits. Our findings show that these infections are frequently underdiagnosed during life and are often only confirmed after death. Persistent fever that does not respond to antibiotics, low white blood cell counts, and organ involvement-especially of the lungs and liver were the main warning signs. While antifungal therapy with amphotericin B can improve outcomes, delays in diagnosis and hesitation to start treatment often led to poor survival. We emphasize that early recognition of symptoms and timely initiation of antifungal therapy, even before laboratory confirmation, can save lives. The study highlights the need for more accurate diagnostic tools and safer antifungal options to reduce mortality in this already fragile group of patients. Keywords: Leukemia; Fungal Infections; Candida; Aspergillus; Amphotericin B; Chemotherapy Complications; Neutropenia 1. Introduction We looked at the medical records of 32 people with acute leukemia who developed serious fungal infections during their chemotherapy. Acute leukemia is fast growing cancer of blood and bone marrow, it also affects WBCs, and symptoms’s like fatigue, fever, and bruising. We found that about 27% of them had these infections, mostly caused by Candida and Aspergillus fungi [1,3,5]. Those with Candida infections usually had very low white blood cell counts for a long time, persistent fevers that didn’t respond to antibiotics, and signs that the fungus had spread through their body. [7,8] When these patients passed away, autopsies showed that Candida had spread widely [7,8]. On the other hand, patients with Aspergillus infections also had low white blood cell counts and fevers, but they showed lung problems right from the time they were admitted [5,9,11]. After death, the fungus was mostly found in their lungs [5,9]. A few patients had both types of infections, and their symptoms were a mix of what we saw with Candida and Aspergillus [3] Only nine patients were diagnosed with fungal infections before they died and all of them had Candida [7,8]. Four of those were treated in time and survived. We realized that these infections are often missed or not treated properly. To improve care, we suggest paying close attention to the situations where these infections tend to happen, using more direct and thorough diagnostic methods, and starting treatment early with antifungal medicine like amphotericin B, Griseofulvin, Fluconazole [15-17,20]. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 404 People with acute leukemia who go through strong chemotherapy often end up getting serious fungal infections, mainly caused by Candida and Aspergillus [1,3,5]. Even though we have antifungal medicines like amphotericin B, these infections still lead to a lot of illness and even death in these patients [1,6,18]. The main reason is that their immune systems are extremely weak, especially when their white blood cell counts drop. But there are also other issues-like delays in spotting and treating the infection that make things worse [7,11,15]. Right now, this vulnerable phase, where the bone marrow stops working and the body can’t fight infections well, is an unavoidable part of treating leukemia successfully. Still, we can do better at managing these fungal infections if we understand what’s causing the delays in diagnosis and treatment [7,11]. Figure 1 Candida One big challenge is that it’s often hard to confirm these infections through lab tests [6,7,14]. In many cases, doctors need to do deep tissue biopsies to get a clear diagnosis, which isn’t always easy or possible [14,15]. To confirm serious fungal infections in leukemia patients, doctors often need to perform invasive tests. But when there’s no clear lab or tissue evidence of infection, many hesitate to use amphotericin B because it can cause strong side effects [17,20]. Table 1 Clinical Findings of Patients with and without Documented Fungal Infections One patient had Torulopsis glabrata with Candida sp. One patient had Cryptococcus with Aspergillus. CANDIDA ASPERGILLUS CANDIDA PLUS ASPERGILLUS MUCOR NO FUNGAL INFECTION No.of patients 17 7 7 1 25 Neutrophils<1,000/mm³ on admission 12 7 6 1 11 Fever on admission>38.5℃ 7 4 6 1 6 One febrile episode 7 7 5 1 18 Two or more febrile episodes 10 0 2 0 6 Pulmonary consolidation on admission 3 6 4 0 7 Developed pulmonary consolidation after starting chemotherapy 13 1 3 1 17 Bacteremia 10 5 5 0 13 Oropharyngeal candidiasis 15 2 6 1 7 Urinary candidiasis 12 1 3 1 7 Hepatomegaly 13 2 5 1 6 World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 405 To tackle these challenges and improve how we care for patients with these infections, we went back and studied the records of all our leukemia patients who had fungal infections. Our aim was threefold: first, to help doctors spot early warning signs of fungal infections more easily; second, to figure out the right time to use more aggressive testing methods; and third, to identify situations where starting amphotericin B treatment early before full confirmation might actually be the right move. 1.1. Retrospective Study of Fungal Infections in Adults with Acute Leukemia Treated at UCSF Medical Center (1973–1980) Between 1973 and 1980, 119 adults with acute leukemia were treated at UCSF Medical Center [1]. Sadly, 105 of them didn’t survive, and autopsies were carried out on 52 of those patients. We went through their hospital and autopsy records to look for signs of serious fungal infections [3,6]. Out of the 52 autopsied patients, 25 showed no fungal infection and were used as a comparison group. The remaining 27, along with five other patients who weren’t autopsied but were confirmed to have fungal infections, formed the main group for our study [3,6,7]. To confirm a fungal infection, we looked for the presence of fungi in tissue, blood, or spinal fluid either through lab cultures or under the microscope [7,14]. If fungi were found in two separate blood samples taken at different times and from different places, we considered that solid proof. But if only one sample tested positive and there was no other evidence, it wasn’t enough to confirm infection [7]. We then studied each patient’s medical history during the time they had the fungal infection [6,8]. We noted their age, gender, type of leukemia, how long and how severe their low white blood cell count was, how often they had fevers, chest x-ray results, physical exam findings, lab results for bacterial or fungal infections, what medications they received, how long they stayed in the hospital, and how many times they had been admitted before for chemotherapy. If the patient survived that hospital stay, we also looked at records from any later hospital visits [6]. 2. Result Upon post-mortem examination 27 of the 52 patients had significant fungal infections. Furthermore prior to their deaths five additional patients who were not autopsied had confirmed fungal infections [3,6]. Of these Candida infections were found in 24 patients [7,8,19]. Seven of those had a combination of Aspergillus and Candida one had both Torulopsis glabrata and Candida (but was included in the Candida-only cases) and sixteen had neither [7,8]. Seven patients had both Candida and Aspergillus one had both Aspergillus and Cryptococcus neoformans (but was included in the Aspergillus-only group) and fourteen patients had Aspergillus infections [5,9,15]. Mucor was the source of an infection in one patient [6]. According to the timeline 11 of the infected patients received treatment between 1973 and 1976 and the remaining 21 received treatment between 1977 and 1980. The number of patients treated for leukemia the type of treatment they received the number of antibiotics used and the number of patients autopsied were among the variables that changed over time [6,18]. The frequency and ease of diagnosis of fungal infections were impacted by these modifications [6]. However autopsied patients before 1977 had a lower prevalence of fungal infections (8 out of 22) than those after 1977 (19 out of 30) [6,18]. Table 2 Number of Induction Hospitalizations and Status of Leukemia at the Time of Death No. of patients First induction Second induction Three or more Hypoplasia Refractory leukemia Recovery of bone marrow Patient with Candida alone 17 6 2 9 8 2 2 Patients with Aspergillus alone 7 4 2 1 5 1 1 Patients with Candida and Aspergillus 7 4 1 2 4 1 2 Patients without fungal infection 25 9 5 11 7 15 3 Include only autopsied patients World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 406 Table I compares the medical details of two groups of patients32 who had fungal infections and 25 who didn’t show any signs of widespread fungal disease when examined after death. Table II gives information about how many times each patient was hospitalized for initial chemotherapy, and what their bone marrow and leukemia condition was like when they passed away. Table III presents what was found during autopsies of the patients who had fungal infections. Among the 17 patients who had Candida infections, one thing was common they all had fevers that didn’t go away even after being treated with strong antibiotics [7,8,19]. Most of them had two separate fever episodes during their hospital stay. The first usually got better with antibiotics, but the second one stuck around. A few patients had just one longlasting fever that never improved [7]. Nearly all of these patients had very low white blood cell counts for a long time, which made it harder for their bodies to fight infections [1,6]. During their hospital stay, Candida was often found in their mouth and urinary tract, and many of them developed an enlarged liver. Other symptoms didn’t really help in telling them apart from patients who didn’t have fungal infections [6]. Most of these patients had leukemia that had come back and were in the advanced stages of their illness [1,6,18]. Sadly, many passed away after about five weeks in the hospital, with bone marrow that had stopped working properly. Autopsies were done on 12 of them, and in nearly every case, the infection had spread to multiple organs like the liver, spleen, lungs, and kidneys none had it limited to just one area [7,8,19]. Treating these infections was mostly unsuccessful. Doctors were able to diagnose Candida infections before death in only nine out of the 17 patients [7,8]. The fungus was most often found in blood samples, followed by spinal fluid, lungs, and liver. Out of those nine, only six received amphotericin B for more than three days at a proper dose [1517,20]. The other eight patients, whose infections were only discovered after death, didn’t get enough of the drug [7,15]. Four patients who were diagnosed and treated did survive that hospital stay, but sadly, they passed away during later admissions. Autopsies on three of them showed that the Candida infection was still active at the time of their death [7,8]. 2.1.1. Aspergillus Seven patients were found to have fungal infections caused only by Aspergillus [5,9]. Most of them had low white blood cell counts, fever, and lung problems when they were admitted to the hospital [9,11]. A few didn’t show these signs right away, but developed fever or lung issues after starting chemotherapy. Antibiotics didn’t help with their symptoms, and there weren’t any other clear signs that could help doctors tell them apart from patients without fungal infections or those with Candida [11]. Table 3 Sites of Autopsy-Proved Organ Involvement of Candlda and Asperglllus Patients with candida alone Patient with aspergillus alone Patients with both candida and aspergillus Number 12 7 7 Candida Aspergillus Lung 10 7 4 7 Liver 11 1 3 1 Spleen 9 1 2 0 Kidney 7 1 2 1 Heart 4 1 2 0 Brain 2 2 1 0 Most of these patients had just been diagnosed with leukemia and were receiving their first round of chemotherapy [1,5]. On average, they stayed in the hospital for about 22 days before passing away, and two of them died within just 10 days of starting treatment. At the time of death, their bone marrow was severely damaged. Autopsies showed that World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 407 all of them had Aspergillus infections in their lungs, and only two had the infection spread to other parts of the body [15,16]. Unfortunately, none of these patients were diagnosed with Aspergillus infection while they were alive, and none received amphotericin B. There were three main reasons for this. First, doctors found bacteria in their blood tests and assumed the lung problems were due to bacterial infections. Second, they were hesitant to perform invasive tests like lung biopsies to find the real cause. And third, they simply didn’t suspect Aspergillus as the source of the infection [9,11]. 2.2. Mixed Fungal Infections Seven patients were found to have infections caused by both Candida and Aspergillus fungi [3,5,9]. When they were first admitted to the hospital, they showed symptoms similar to those seen in patients with only Aspergillus infection slow white blood cell counts, fever, and lung issues [9,11]. As their hospital stay progressed, they developed signs more typical of Candida infections, such as mouth and urinary tract infections, and enlarged liver [7,8,19]. Unfortunately, none of these fungal infections were diagnosed while they were alive, and they didn’t receive any antifungal treatment [6,15]. As a result, their fevers and lung problems didn’t improve. On average, they stayed in the hospital for about 21 days before passing away, which was similar to patients who had only Aspergillus infections [5,9]. After death, autopsies revealed that Candida had spread throughout their bodies, while Aspergillus was mostly limited to the lungs [5,7]. 2.2.1. Comment Patients with acute leukemia who undergo strong chemotherapy often face serious fungal infections, which can be lifethreatening [1,3,5,6]. Diagnosing these infections is tricky and uncertain, so doctors sometimes use a powerful antifungal drug called amphotericin B without waiting for test results [15-17,20]. But because this drug has harsh side effects, many doctors hesitate to use it unless they have clear proof of infection. Unfortunately, this delay has led to several deaths from fungal infections at our hospital [6,7,11]. In our review of cases from 1973 to 1980, we found 32 patients who had confirmed fungal infections [1,3,5]. Most of these were only discovered after the patients had passed away, during autopsies. That means the actual number of infections was likely much higher than what we recorded27% is just the minimum. Over time, the risk seems to have grown, likely because treatments have become more intense, causing longer periods of low immunity and more use of strong antibiotics [18,19]. Just like other studies have shown, the main culprits behind these infections in our leukemia patients were Candida and Aspergillus fungi [1,3,5]. 2.2.2. Candida In our experience, patients with widespread Candida infections usually had very low white blood cell counts for a long time after starting chemotherapy [1,3,18]. They also had persistent fevers that didn’t respond to antibiotics, and visible signs of Candida infection in places like the mouth and throat. These symptoms were common in nearly all our patients with serious Candida infections, and when we saw this combination, it often meant the infection had spread throughout the body [7,8]. Some patients also had enlarged livers and lung issues, but these signs appeared later and weren’t helpful for early diagnosis [7,12]. It seems that Candida starts by invading areas where it’s already present on the surface, like the mouth or gut. From there, it enters the bloodstream and spreads to other organs, forming small pockets of infection. Since the gut is likely the main entry point, liver and spleen swelling is often seen [8,19]. We struggled to diagnose and treat these infections effectively. The main reasons were: doctors didn’t suspect Candida unless lab tests confirmed it [6,7], treatment wasn’t started until then, and by that time, the infection was usually advanced and the patient was very sick [7,8,11]. To improve outcomes, we now begin treatment early with amphotericin B if a patient has low white blood cells, ongoing fever, and visible Candida infection [16,17,20]. We start with a small test dose and gradually increase it. Treatment continues until the patient’s white blood cell count recovers. If there’s strong evidence of infection at that point, we complete the full course. If not, we stop the drug and monitor the patient closely [17,20,21]. Using this approach might mean some patients get the drug unnecessarily, but it also helps us catch infections early. In our study, four patients who were treated survived and came back later for more leukemia treatment. Sadly, they died during that stay, and autopsies showed the Candida infection had returned and spread widely [7,8]. This shows that Candida is hard to eliminate and can come back during future periods of low immunity. Starting treatment early may help control the infection better. And if a patient has had Candida before, we should be alert for its return and treat it quickly [16,17,20]. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 403–409 408 2.2.3. Aspergilus In patients with Aspergillus infections, we often saw a combination of fever, low white blood cell count (neutropenia), and lung problems right when they were admitted or shortly after [5,6,9,11]. This suggests that the infection was already present before chemotherapy started or developed very early during treatment. Sadly, some patients died just days after beginning chemotherapy, showing how quickly Aspergillus can become fatal. Many of these patients had just been diagnosed with leukemia and hadn’t started any treatment yet, so their deaths cut short a real chance at recovery [1,5]. Because of how often and how early Aspergillus shows up, we’ve changed how we handle lung issues that appear soon after a patient is admitted. We now act fast to get tissue samples for testing either through a bronchoscopy (a scope into the lungs) or an open lung biopsy [14]. At the same time, we start broad antibiotics. If the bronchoscopy doesn’t give us answers, we move to the biopsy. If we still don’t have a clear diagnosis and antibiotics aren’t working, we start antifungal treatment with amphotericin B. The dosing is similar to how we treat Candida infections, but we increase the dose to 1 mg/kg by the fourth day if the patient can tolerate it [15,17]. This early treatment approach would have helped most of our patients with Aspergillus infections, and only a few would have received the drug unnecessarily. One important lesson from our data is that early blood tests often showed bacterial growth, which misled doctors into thinking the lung issues were bacterial. As a result, they stuck with antibiotics even when patients weren’t improving and didn’t pursue further testing. So now, when antibiotics don’t clear up lung problems quickly, we stay alert for Aspergillus and either push for a clear diagnosis or start antifungal treatment early [15,17,20]. 2.2.4. Mixed Infection Seven of our patients were found to have both Candida and Aspergillus infections [3,5]. Their symptoms and test results showed a mix of what we typically see in each of these fungal diseases Candida affecting the whole body and Aspergillus mainly targeting the lungs [7-8,11]. It looked like the Aspergillus infection started first, and then Candida spread later during their hospital stay. Sadly, most of these patients died early, likely because of the Aspergillus infection [3,5]. From what we’ve seen, treating the Aspergillus infection early is crucial for giving leukemia patients a better chance at recovery. If we start antifungal treatment with amphotericin B right away when Aspergillus is suspected, it may help prevent Candida from spreading throughout the body later on [15-17,20]. 3. Conclusion Fungal infections remain one of the most serious and life-threatening complications faced by patients with acute leukemia undergoing intensive chemotherapy. Our review of clinical findings clearly shows that Candida and Aspergillus are the two most frequent causes, each presenting with distinct yet often overlapping signs. Unfortunately, most infections were only discovered after patients had passed away, highlighting how easily these conditions can be overlooked when fevers and lung issues are assumed to be bacterial in origin. The biggest barrier to timely treatment is the difficulty of early and accurate diagnosis, since confirmatory tests often require invasive procedures that are not always possible in critically ill patients. Despite the risks of side effects, our study supports the early use of antifungal therapy especially amphotericin B when patients show consistent warning signs such as prolonged fever unresponsive to antibiotics, severe neutropenia, and evidence of Candida or lung involvement suggestive of Aspergillus. Acting early, even before absolute confirmation, could improve survival chances and prevent widespread infection. While this may mean that some patients are treated unnecessarily, the potential to save lives outweighs the risks of cautious hesitation. Looking forward, better diagnostic tools, safer antifungal drugs, and preventive strategies are urgently needed. Until then, physicians should remain highly alert to the early signs of fungal infection and intervene quickly. By combining vigilance, early decision-making, and ongoing improvements in therapy, we can reduce the burden of fungal infections and offer leukemia patients a better chance at recovery and quality of life. 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