A 48-year-old Colombian female, Caucasian, without relevant personal or familiar medical history, who had been diagnosed with early T cell precursor ALL, with high-risk criteria due to her age and malignancy subtype who was initially treated with the PETHEMA ALL AR 2011 protocol, and with prophylactic intrathecal chemotherapy, starting in January of 2022.
During her initial hospital stay, she presented with fever, along with chest computed tomography findings of ground-glass nodules in the lungs (Fig. 1) and was started on Voriconazole, due to a high suspicion of invasive pulmonary aspergillosis infection.
The assessment of serum galactomannan was negative. Subsequently she exhibited a rise in aminotransferase levels over 6 times the upper limit of normal, along with conjugated hyperbilirubinemia. After performing magnetic resonance imaging, autoantibody tests, serologies for hepatotropic viruses and a liver biopsy, which ruled out fungal infection or infiltration due to her hematologic malignancy, it was concluded that she was experiencing drug toxicity due to her antifungal treatment. Therapy was changed to Isavuconazole which was administered for about 2 weeks.
Despite these efforts, the patient had recurrent fever episodes and lung nodules persisted. A bronchoscopy with bronchoalveolar lavage was performed, but no relevant pathogens where isolated in the samples. SARS-COV-2, Tuberculosis molecular assays, Galactomannan and fungal cultures were negative.
Multiple cervical lymphadenopathies of several centimeters in diameter where later detected. A biopsy was performed to rule out possible T cell lymphoblastic leukemia or a systemic mycosis, which had not been identified up to that moment. Ziehl-Neelsen stain and polymerase chain reaction assays for tuberculosis were negative, but the histopathologic study exhibited chronic necrotizing granulomatous inflammation, with large areas of liquefactive necrosis, containing Paracoccidioides brasiliensis yeasts (Figs. 2, 3).
Following this, infectious disease specialists determined treatment with Liposomal Amphotericin B, and after 1 week of treatment fever seized, cervical lymph node size gradually reduced, and 3 weeks later, lung nodules disappeared.
Regarding ALL, the treatment was resumed and after completion of the chemotherapy regimen, flow cytometry was performed in a bone marrow sample, which reported 0.4% of lymphoblasts, and MPO deficiency, depicted in Fig. 4, where flow cytometry shows different white cell populations as polymorphonuclear neutrophils and monocytes negative for MPO fluorescence, as an incidental finding as shown. This discovery correlates with the presence of Large Unstained Cells (LUC)/false neutropenia in the complete blood count, with a normal peripheral blood smear.
As part of the treatment of the ALL a haploidentical allogenic stem cell transplant process was later initiated. During this process, she had multiple infectious complications, intestinal bleeding, and cholestasis, which lead to the discontinuation of liposomal amphotericin B. Antifungal treatment was stopped for 2 weeks and was later restarted using Trimethoprim/Sulfamethoxazole as indicated by the infectious diseases specialist. By that time, a control chest computed tomography did not report any lung nodules.
During her bone marrow transplant recovery and engraftment, findings consistent with resolution of the MPO deficiency were noted (increase in the number of positive MPO neutrophils in the blood count). Finally, after making a complete recovery, she was discharged, and treatment with Trimethoprim/Sulfamethoxazole was continued for 12 additional months. Two weeks after discharge, a new blood count was obtained, which showed MPO positive neutrophils and stability of the graft.