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An event is serious (based on the ICH definition) when the patient outcome is:

  • * death

  • * life-threatening

  • * hospitalisation

  • * disability

  • * congenital anomaly

  • * other medically important event

A 30-year-old woman developed disseminated mucormycosis during treatment with asparaginase, cyclophosphamide, daunorubicin, prednisolone and vincristine for acute lymphoblastic leukaemia (ALL). Additionally, she developed bacterial sepsis while receiving fludarabine and melphalan as conditioning regimen and tacrolimus and methotrexate as for graft-versus-host disease (GvHD) prophylaxis [routes not stated].

The woman was diagnosed with B-cell ALL and started receiving induction therapy comprising cyclophosphamide 1200 mg/m2, asparaginase 6000 IU/m2 [L-asparaginase], daunorubicin 45 mg/m2, prednisolone 90 mg/day and vincristine 2 mg/day. She also received concomitant preventive therapy with levofloxacin, fluconazole and valaciclovir. On day 21 of the therapy, she developed pain in her left shoulder and upper abdomen. Her vital signs were as follows: body temperature 38°C, oxygen saturation 99% on room air, and clear respiratory sounds. CT scan showed an abscessed lesions in organs, including the liver, kidney and spleen and a reversed halo sign around the left pulmonary apex region. Test for Serum β-D-glucan, galactomannan and blood cultures were negative. Subsequently, she was suspected with disseminated mucormycosis, which was suspected to be secondary to the induction chemotherapy.

The woman's chemotherapy was immediately discontinued because of serious infection. She was treated with broad-spectrum antibiotic under the suspicion of febrile neutropenia. She received amphotericin-B [liposomal amphotericin-B] in combination with micafungin. The dose of amphotericin was further increased while monitoring the her tolerance. She was also treated with unspecified granulocyte colony stimulating factors. At day 28, she recovered from myelosuppression. She also achieved complete remission from ALL. On day 30, a trans-bronchoscopic lung biopsy and bronchoalveolar lavage were performed. Histopathological examination of the lung tissue showed fungal hyphae invading the blood vessels with broad irregular non-septate hyphae with right angles. Considering the morphological features, the mold was classified as order Mucorales. The findings led to the diagnosis of disseminated mucormycosis with the lung as the primary lesion. To control the main fungal lesions, amphotericin-B and micafungin were continued. On day 27, she underwent left upper lobectomy after the onset of mucormycosis. This intervention was necessary to reduce the risk of further dissemination from the lung to other organs. Following surgical intervention, three additional consolidation therapies were administered with concurrent antifungal agents. A physical examination revealed that her abdominal findings had disappeared. However, a mild fever persisted. Blood test showed slightly high C-reactive protein concentration and enhanced CT scan revealed presence of abscessed lesion, smaller and encapsulated. Based on these findings, it was found that the fungal infection activity not completely controlled. Eventually, her renal function worsened. But, ALL remained in complete remission. It was difficult to continue long-term consolidation therapy as well as maintenance therapy along with antifungal agents. Therefore, bone marrow stem cell transplantation (BMT) was planned. Thus, she received conditioning regimen with fludarabine 150 mg/m2and melphalan 140 mg/m2. She also received tacrolimus 0.02 mg/kg and methotrexate 5 mg/m2 for graft-versus-host disease (GvHD) prophylaxis. Her antifungal treatment was continued at the same dose before and after transplant and cefepime was added. On day 20 after transplantation, engraftment was confirmed. Subsequent, CT showed shrinking of residual fungal lesions were over time. Also, the C-reactive protein level reduced to zero. It was determined that the fungal infection activity had almost gone. During myelosuppression, she was complicated with bacterial sepsis. However, she did not develop any transplant related complications or relapse of fungal infections. From day 60 after transplantation, her creatinine level increased 5 mg/dL. At that time, the antifungal treatment was gradually reduced over a period of about one month. The antifungal treatment was entirely discontinued on day 273 following the onset of mucormycosis. Treatment with tacrolimus was continued. Thereafter, her renal function improved. ALL remained in complete remission without recurrence of mucormycosis. On day 101 after transplantation, she was discharged in good condition. Over 1.5 years following BMT, she remained in complete remission from ALL without mucormycosis recurrence [not all duration of treatments to reactions onsets and outcomes stated].