Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy that predominantly affects children and young adults and is associated with favorable outcomes when treated with contemporary risk-adapted chemotherapy protocols 12. However, relapsed ALL continues to pose a major therapeutic challenge, often requiring intensive salvage chemotherapy and prolonged corticosteroid exposure, leading to profound immunosuppression and increased susceptibility to opportunistic infections 23.

Invasive fungal infections are a significant cause of morbidity and mortality in patients with ALL, particularly in the relapsed or refractory setting 4. Among these, mucormycosis is a rare but rapidly progressive angioinvasive fungal infection caused by fungi of the order Mucorales5. It primarily affects immunocompromised hosts, including patients with hematological malignancies, and is associated with high mortality rates despite advances in antifungal therapy 6. Pulmonary and rhino-orbito-cerebral forms are most frequently reported; however, disseminated disease with renal involvement is uncommon and often underdiagnosed 67.

Early diagnosis of mucormycosis is challenging due to nonspecific clinical manifestations and limited sensitivity of routine diagnostic modalities 57. While histopathological confirmation remains the gold standard, rapid and accessible techniques such as direct microscopy and fungal culture from clinical specimens can play a crucial role in early detection, particularly in disseminated disease where tissue sampling may be difficult 78.

Here, we report a case of disseminated mucormycosis involving the lungs and kidneys in a patient with relapsed pre-B acute lymphoblastic leukemia, diagnosed through urine KOH microscopy and urine fungal culture, and successfully managed with ECIL-guided antifungal therapy 8910. This case highlights the importance of early suspicion, detailed clinical history by patient and reletives, and timely guideline-directed treatment in improving outcomes in high-risk ALL patients.

A 28-year-old male was diagnosed with relapsed Pre-B acute lymphoblastic leukemia at Rajkot. He received chemotherapy according to the BFM 2002 protocol and completed treatment in October 2023, and maintenance was completed after 2 and half years. Subsequently, the patient developed disease relapse. Flow cytometric analysis confirmed pre-B ALL. Cytogenetic evaluation demonstrated a normal karyotype (46, XY). Next-generation sequencing (NGS) revealed a MEF2D-BCL9 fusion along with multiple copy number variations involving chromosomes 10, 12, and 19, indicating high-risk disease biology.

In view of relapsed disease, he was started on salvage therapy using bortezomib-based Children’s Oncology Group (COG) protocol, with a treatment plan to proceed to allogeneic stem cell transplantation or CAR-T cell therapy based on response. The patient received prednisolone 40 mg/day, vincristine (1.4mg/m² on Days 1, 8, and 15), Bortezomib (1.3 mg/m^² on Days 1, 8, and 15), Doxorubicin (60 mg/m^² on Day 1), Peg-asparaginase (1000 units/m^² on Days 3, 10, and 18) (Figure 1).

His clinical course was relatively uneventful for the first three weeks of therapy. After three weeks, he developed acute liver injury, which was attributed to the ongoing chemotherapy. With supportive care, his bilirubin levels and transaminases began to resolve. He subsequently developed minimal cough and fever, which were initially attributed to a viral illness, along with the presence of white patches in the oral cavity. In response, steroid tapering was initiated, and oral posaconazole was started empirically. Over the next week, the patient developed urinary urgency, lower abdominal pain, and fever (101°F) and presented to the hospital for further treatment. During hospitalization, urine potassium hydroxide (KOH) examination demonstrated the presence of broad, aseptate fungal hyphae suggestive of Mucor species.

Following this finding, a detailed retrospective history was obtained from the patient and his relatives. It was then revealed that approximately 10 days after the initiation of steroid tapering, the patient experienced right-sided chest pain, cough, and one to two episodes of haemoptysis, which had not been reported earlier. Subsequently, the patient developed hypoalbuminemia and acute kidney injury (AKI).

Patients with acute lymphoblastic leukemia (ALL), particularly those with relapsed disease, are at high risk for invasive fungal infections due to profound immunosuppression caused by intensive chemotherapy, prolonged neutropenia, and corticosteroid exposure. Among these infections, mucormycosis is uncommon but highly aggressive, with mortality rates exceeding 40–50% in patients with hematological malignancies 46.

Relapsed ALL further amplifies this risk because of cumulative treatment-related toxicity, immune dysfunction, and metabolic derangements. Mucormycosis in ALL most frequently involves the lungs or rhino-orbito-cerebral region; however, disseminated disease with renal involvement, as seen in this patient, is rare and reflects severe immune compromise 67. The angioinvasive nature of Mucorales leads to vascular thrombosis, tissue necrosis, and rapid progression, making early recognition critical for survival 5.

Early diagnosis of mucormycosis remains challenging, as clinical and radiological findings are often nonspecific, and tissue biopsy is frequently difficult in patients with thrombocytopenia or critical illness. While histopathology remains the diagnostic gold standard, direct microscopy and fungal culture from clinical specimens play an important supportive role, particularly in disseminated disease 78.

In this case, identification of broad, ribbon-like, aseptate hyphae on urine KOH examination, along with growth of Mucor species on urine fungal culture, was instrumental in early diagnosis. Detection of Mucor in urine is uncommon but strongly suggestive of renal or disseminated mucormycosis, especially when correlated with imaging findings such as emphysematous pyelonephritis. These rapid, low-cost diagnostic modalities enabled early initiation of targeted antifungal therapy prior to tissue confirmation, emphasizing their value in high-risk ALL patients 78.

The key learning point in this case was the absence of an initially reported history of respiratory illness. It was only after the microbiology laboratory reported features suggestive of mucormycosis on KOH examination of the urine sample that a detailed re-enquiry was made. At that time, the patient’s relative disclosed a history of respiratory symptoms for the preceding 15 days, which had not been volunteered earlier. This crucial information subsequently prompted targeted radiological evaluation of the lungs and kidneys, leading to further diagnostic clarification.

Management of mucormycosis in patients with ALL requires urgent initiation of antifungal therapy, correction of underlying predisposing factors, and surgical intervention when feasible. According to ECIL (European Conference on Infections in Leukemia) guidelines, high-dose liposomal amphotericin B is the first-line treatment for mucormycosis and carries a strong recommendation (A-II) for patients with hematological malignancies 9.

ECIL further recommends early initiation of antifungal therapy without delay for definitive histopathological confirmation in patients with strong clinical suspicion, as treatment delay is associated with significantly increased mortality. Isavuconazole and posaconazole are recommended as salvage or step-down therapy (B-II), particularly in patients with renal impairment or intolerance to amphotericin B 910.

In the present case, surgical intervention was not feasible due to extensive bilateral pulmonary and renal involvement. Therefore, management followed ECIL-guided medical therapy using liposomal amphotericin B, followed by addition of isavuconazole, which is supported by ECIL recommendations for severe or disseminated mucormycosis when surgical options are limited. Isavuconazole offers the advantage of a favorable safety profile, predictable pharmacokinetics, and reduced nephrotoxicity, making it particularly suitable in ALL patients with evolving renal dysfunction 91011.

The patient’s clinical improvement, stabilization of renal function, and rising serum albumin levels highlight the importance of early ECIL-guided antifungal therapy and individualized treatment strategies in managing mucormycosis complicating ALL.

Patients with relapsed acute lymphoblastic leukemia are at a high risk of developing invasive fungal infections, including mucormycosis, due to profound immunosuppression related to intensive chemotherapy and corticosteroid exposure. This case highlights disseminated mucormycosis with pulmonary and renal involvement as a rare but life-threatening complication in an ALL patient. Early identification of Mucorales through urine KOH microscopy and urine fungal culture proved crucial in establishing the diagnosis and enabling prompt initiation of antifungal therapy. Management in accordance with ECIL recommendations, including early administration of high-dose liposomal amphotericin B and adjunctive isavuconazole when surgical intervention was not feasible, resulted in clinical stabilization and organ function improvement. This case underscores the importance of maintaining a high index of suspicion for mucormycosis in high-risk ALL patients and demonstrates that early, guideline-directed antifungal therapy can be lifesaving even in disseminated disease.