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Year : 2019  |  Volume : 8  |  Issue : 3  |  Page : 215-218

Unusual cause of intestinal perforation during induction chemotherapy in acute myeloid leukemia

Department of Medical Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

Date of Submission09-Aug-2019
Date of Acceptance16-Aug-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Dr. Rajani Priya Yedla
Department of Medical Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, Telangana
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Source of Support: None, Conflict of Interest: None


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Primary intestinal aspergillosis is a rare but serious infectious complication with a high morbidity and mortality in immunocompromised patients. We report a case of 47-year old male diagnosed with acute myeloid leukaemia and started on induction chemotherapy. On day 18 of chemotherapy, he presented with an acute abdomen and underwent emergency exploratory laparotomy. Histopathological specimen revealed transmural necrosis with fungal hyphae due to aspergillosis and voriconazole was started. Serum galactomannan test done was negative. In the post-induction chemotherapy, he attained complete remission and received three cycles of consolidation with high-dose cytarabine. With this case, we would like to emphasize that early recognition of primary intestinal aspergillosis is of the utmost importance because of its fulminant clinical course. It should be included in the differential diagnosis of neutropenic patients with sudden onset abdominal pain and ongoing fever, even in the absence of a positive serum galactomannan.

Keywords: Acute myeloid leukemia, aspergillosis, intestinal perforation

How to cite this article:
Yedla RP, Bala S, Uppin MS, Gundeti S. Unusual cause of intestinal perforation during induction chemotherapy in acute myeloid leukemia. J NTR Univ Health Sci 2019;8:215-8

How to cite this URL:
Yedla RP, Bala S, Uppin MS, Gundeti S. Unusual cause of intestinal perforation during induction chemotherapy in acute myeloid leukemia. J NTR Univ Health Sci [serial online] 2019 [cited 2022 Aug 11];8:215-8. Available from: https://www.jdrntruhs.org/text.asp?2019/8/3/215/269492

  Introduction Top

Treatment of acute myeloid leukemia with standard induction chemotherapy causes prolonged myelosuppression and mortality from invasive fungal infections.[1] The most common fungal infections are Candida, Aspergillosis, and Mucormycosis,[2] the sites being blood, lungs, paranasal sinuses. We report a rare case of intestinal perforation caused by Aspergillus.

  Case Report Top

A man aged 47 years without any co-morbidities presented with high-grade fever for a month and melena for 10 days. A hemogram suggested acute leukemia. Examination showed pallor, without lymphadenopathy or organomegaly. Systemic examination was normal. A complete blood count (CBC) showed anemia (6 g/dL), thrombocytopenia (20 × 109/L), and leucocytosis (74 × 109/L) with 95% myeloblasts. Peripheral blood cytochemistry showed sudan back blue and myeloperoxidase positivity of myeloblasts. Bone marrow aspiration and biopsy showed increased cellularity with 90% myeloblasts [Figure 1]. Flow cytometry characterized the blasts as positive for cytoplasmic myeloperoxidase, moderate CD117, CD33, dim CD38, which was consistent with acute myeloid leukemia (AML)-M1. Cytogenetics was normal and mutation panel revealed NPM1 mutation.
Figure 1: Peripheral smear showing Blastsx 400× (b) Trephine imprints showing 90% blasts which are 2–3 times the size of small lymphocyte with scant cytoplasm and fine granules,  Auer rods More Details not seenx 100×. (C) SBB Stain showing positivity in the blastsx 100×

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He was stratified as favorable risk AML and was started on standard induction chemotherapy with daunomycin and cytarabine (7 + 3 regimen). On day 8, he developed fever without any localizing signs. After sending blood cultures, he was started on meropenem. Blood cultures revealed no growth. On day 11, he developed fever with no localizing symptoms. He was started on empirical antifungal therapy with Amphotericin-B. Blood cultures sent again showed no growth. On day 15, he became breathlessness with cough. High-resolution computed tomography of chest showed right lower lobe consolidation. He was started on vancomycin. Serum galactomannan was negative. He had persistent fever spikes despite these antibiotics.

On day 18 of chemotherapy, he developed abdominal pain with distension. He had diffuse tenderness with guarding. Plain computed tomography of abdomen revealed pneumoperitoneum with jejunal wall thickening [Figure 2] An emergency exploratory laparotomy was performed. Two perforations of size 2.5 × 2.5 cm and 1.5 × 1.5 cm with sloughed margins were noted along the antimesenteric border of jejunum. A wedge resection of perforation site and anastomosis were done. Postoperative period was uneventful. Histopathological examination of the resected specimen revealed transmural necrosis with slender broken septate hyphal structures resembling fungal organisms consistent with Aspergillus species [Figure 3], [Figure 4], [Figure 5]. Serum galactomannan sent on day 22 was negative. Pathogenic fungi from resected material could not be cultured. Amphotericin was stopped in view of persistent hypokalaemia and he was started on voriconazole. The day-33 of bone marrow examination showed complete remission. He received 3 cycles of consolidation chemotherapy post induction with high-dose cytarabine. He received voriconazole for 12 weeks followed by prophylactic voriconazole till completion of chemotherapy. He is on regular follow-up and is disease-free 8 months post completion of chemotherapy.
Figure 2: CT plain abdomen showing pneumoperitoneum and circumferential wall thickening (8 mm) involving jejunal loop

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Figure 3: Wall of jejunum (a) [H and E × 40] with area of perforation showing transmural necrosis with ulcerated mucosa (b) [H and E × 40]

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Figure 4: There is dense inflammatory infiltrate in the submucosa (a) [H and E × 40] extending through the muscularis propria (b) [H and E × 40]. Higher magnification shows lymphomononuclear infiltrate (c) [H and E × 100]

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Figure 5: Special stains for fungal organisms highlights hyphal structures [Silver methenamine]

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  Discussion Top

Availability of novel agents in the last decade and improvements in supportive care have improved outcomes in AML.[1] Remission induction chemotherapy for AML causes prolonged myelosuppression rendering patients susceptible to a wide variety of bacterial and fungal pathogens resulting in serious infections and compromising outcomes.

Fungal infections are an important cause of mortality and morbidity in immunocompromised patients, particularly in those with neutropenia or impaired neutrophil function. Patients on AML induction chemotherapy are at greater risk of developing invasive aspergillosis because of prolonged neutropenia. Use of prophylactic antimicrobials and emergence of fluconazole-resistant Candidial species and non-Aspergillus molds have placed a greater emphasis on the selection of broader-spectrum agents for empirical therapy of invasive fungal infections in this high-risk population.

Aspergillus species are ubiquitous saprophytic spore-producing fungi commonly found in the environment. Out of approximately 200 species, Aspergillus fumigatus is responsible for majority of cases of invasive aspergillosis. Other potential species include Aspergillus niger, Aspergillus flavus, and Aspergillus terreus.[3]Aspergillosis of the gut has been reported in association with disseminated fungal disease and rarely as a primary event. The associated mortality rate has been quoted at 47–60%, with significant rates of morbidity.[4]

In contrast to Candida spp., Aspergillus spores may not survive or meet favorable conditions to develop on the mucosal surfaces of the digestive tract. However, large ulcers, such as those described as occurring after high-dose cytarabine-related mucositis, may be colonized by Aspergillus spores. Most of the times, Aspergillosis of gut is an autopsy finding, because of nonspecific clinical and radiological findings.

Patients with gastrointestinal aspergillosis can present as neutropenic enterocolitis (typhlitis), appendicitis, ileus, colonic ulcers, abdominal pain, or GI bleeding.[5] A common biomarker in clinical use for invasive aspergillosis is the galactomannan assay. Galactomannan is an Aspergillus cell wall component that is released during Aspergillus growth. The assay can be used as a surveillance marker, or as a direct diagnostic tool. A meta-analysis showed that galactomannan assay had a sensitivity of 0.71 and specificity of 0.89 for proven cases of invasive aspergillosis.[6] In the present case, serum galactomannan done twice was negative.

Raoul Herbrecht et al. compared voriconazole versus Amphotericin B for primary therapy of invasive aspergillosis. They showed superiority of voriconazole over amphotericin B in terms of response rate, survival rate, and safety.[7]

The present case reiterates diagnosing infections during induction chemotherapy in hematological malignancies so that administration of antibiotics and antifungals helps in improving the outcomes in hematological malignancies.

  Conclusions Top

Early diagnosis of invasive fungal infections in patients with AML on induction chemotherapy is difficult but essential to reduce mortality. A high index of suspicion for invasive gastrointestinal aspergillosis in immunocompromised patients presenting with acute abdominal symptoms is needed. Early surgical intervention in addition to aggressive antifungal treatments improves outcomes. Our patient recovered with timely surgical intervention and voriconazole use.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Nucci M, Anaissie E. How we treat invasive fungal diseases in patients with acute leukemia: The importance of an individualized approach. Blood 2014;124:3858-69.  Back to cited text no. 1
Safdar A, Difficulties with fungal infections in acute myelogenous leukemia patients: Immune enhancement strategies. Oncologist 2007;12(Suppl 2):2-6.  Back to cited text no. 2
Cornillet A, Camus C, Nimubona S, Gandemer V, Tattevin P, Belleguic C, et al. Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: A 6-year survey. Clin Infect Dis 2006;43:577-84.  Back to cited text no. 3
Eggiman P, Chevrolet M, Starobinski M, Majno P, Totsch M, Chapuis B, et al. Primary invasive aspergillosis of the digestive tract: Report of two cases and review of the literature. Infection 2006;34:333-8.  Back to cited text no. 4
González-Vicent M, Díaz MA, Colmenero I, Sevilla J, Madero L. Primary gastrointestinal aspergillosis after autologous peripheral blood progenitor cell transplantation: An unusual presentation of invasive aspergillosis. Transpl Infect Dis 2008;10:193-6.  Back to cited text no. 5
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis 2006;42:1417-27.  Back to cited text no. 6
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus Amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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