Isavuconazole in a Successful Combination Treatment of Disseminated Mucormycosis in a Child with Acute Lymphoblastic Leukaemia and Generalized Haemochromatosis: A Case Report and Review of the Literature

Abstract

Invasive mucormycosis in immunocompromised children is a life-threatening fungal infection. We report a case of a 7-year-old girl treated for acute lymphoblastic leukaemia complicated by disseminated mucormycosis during induction therapy. Microscopic examination of surgically removed lung tissue revealed wide, pauci-septate hyphae suggesting a Mucorales infection. This diagnosis was confirmed immunohistochemically and by PCR analysis followed by a final identification of Cunninghamella sp. The patient was treated successfully with surgical debridement and antifungal combination therapy with amphotericin B, caspofungin and isavuconazole. The use of isavuconazole in a child was not previously reported. Additionally, case reports concerning pulmonary mucormycoses in paediatric population published after 2010 were reviewed. Nineteen out of 26 identified patients suffered from haematological diseases. Reported mortality reached 38.5%. By the fact of rising morbidity, unsatisfactory results of treatment and remaining high mortality of mucormycoses in immunocompromised patients, new therapeutic options are warrant. Isavuconazole, with its broad-spectrum activity, good safety profile and favourable pharmacokinetics, is a promising drug. However, further studies are necessary to confirm positive impact of isavuconazole on mucormycosis treatment in children.

Mucormycosis diagnosed during induction chemotherapy in five pediatric patients with acute lymphoblastic leukemia

“…Unlike posaconazole, it does not require administration with food and does not cause QTc prolongation. There is overall less experience with the use of isavuconazole, and it is not yet approved for use in children, but one case report describes its successful use in a seven‐year‐old with ALL and invasive mucormycosis …”

“…There is overall less experience with the use of isavuconazole, and it is not yet approved for use in children, but one case report describes its successful use in a seven-year-old with ALL and invasive mucormycosis. 3 The treatment of ALL when invasive mucormycosis is diagnosed in the early stage of induction chemotherapy is challenging. Rapidly achieving remission through chemotherapy dose intensity is critical, but this must be balanced against the potentially devastating risks of severe immunosuppression in the setting of IFI.…”

“…Mucormycosis during induction for acute lymphoblastic leukemia (ALL) is not well described in the literature, other than a few case reports . We describe five cases of mucormycosis that developed during induction therapy for ALL at our institution between 2011 and 2018.…”

“…Mucormycosis during induction for acute lymphoblastic leukemia (ALL) is not well described in the literature, other than a few case reports. [1][2][3] We describe five cases of mucormycosis that developed during induction therapy for ALL at our institution between 2011 and 2018. This article seeks to raise awareness of mucormycosis during induction therapy for pediatric ALL and describe the modifications made to each patient's chemotherapy regimen and the complications that developed over the course of several years of combined leukemia and antifungal therapy to identify important clinical considerations for long-term management.…”

Diagnostic performance of immunohistochemistry for the aspergillosis and mucormycosis

“…We retrieved epitopes from steaming at 96°C either for manual staining for 60 minutes in 10 mmol/L citrate buffer (pH 6.0) or for autostainer for 1 hour in ethylene diamine tetraacetic acid (pH 8.0). The samples were incubated with anti‐ Rhizopus arrhizus mouse monoclonal antibody (1:100; clone WSSA‐RA‐1; LSBio) at room temperature for 1 hour or anti‐ Aspergillus mouse monoclonal antibody (1:50; clone WF‐AF‐1; LSBio) in autostainer. Afterwards, sections were incubated for 30 minutes with the Dako Envision System Kit (K5007; Dako) and developed with 3, 3’‐diaminobenzidine (DAB) solution (Dako) for manual staining or with an optiView Universal DAB kit (Ventana Medical Systems) in autostainer.…”