LAUSR

Dear Editor, Blinatumomab is a T cell engager antibody with bi-specificity for CD3 and CD19. By binding to both antigens, blinatumomab directs CD3+ cytotoxic T cells to destroy CD19-expressing neoplastic B cells. The spectrum of B cell malignancies targeted ranges from B cell acute lymphoblastic leukemia (ALL) (both Philadelphia chromosome positive, Ph+, and Ph−negative) [1–3] to diffuse large B cell lymphoma [4, 5]. A 31-year-old woman presented with Ph+ ALL. Complete remission was achieved with combination chemotherapy and imatinib. She then received two years of imatinib maintenance. Four years later, she was referred for leukemia relapse. Chemotherapy (idarubicin, cytarabine, etoposide) combined with dasatinib resulted in a second remission. About three months later, the disease relapsed. A third remission was achieved after salvage treatment (methotrexate, vincristine, L-asparaginase). During periods of leucopenia, she developed multiple episodes of reactivation of herpes simplex virus and cytomegalovirus infection, which were controlled by valaciclovir and ganciclovir, respectively. Anti-fungal prophylaxis with micafungin was administered continuously, with no documented episodes of invasive fungal disease (IFD), despite prolonged periods of neutropenia lasting for more than three months. While evaluated for allogeneic hematopoietic stem cell transplantation, she relapsed again. Via a compassionate program and with informed consent, she was treated with blinatumomab. During the first week (dose: 9 μg/day), she developed seizure and acute subarachnoid hemorrahge, necessitating transient cessation of therapy. After a break of about a week, blinatumomab therapy was recommenced and successfully stepped up to 28 μg/day without further neurological problems. On day 24 of blinatumomab therapy, she developed a high fever accompanied by the appearance of rashes over her arms, legs, and face. Close inspection gave a suggestion of early vesicle formation (Fig. 1a, b). Chest X-ray showed new-onset bilateral lower zone haziness (Fig. 2a). Owing to multiple previous episodes of herpes viral reactivation, disseminated varicella zoster viral infection was empirically diagnosed. She was kept in reverse isolation, and started on intravenous acyclovir. In the next two days, crops of skin eruptions appeared, with blistering to necrotic centers (Fig. 1c). On the third day, blood culture showed yeasts . Micafungin was stopped, and l iposomal amphotericin B (ambisome; 150 mg/day) was started. Two days later, the yeast was identified as Trichosporon asahii. Skin swab was negative for varicella zoster virus on polymerase chain reaction, but was culture-positive for Trichosporon asahii. A skin biopsy also showed the presence of fungal elements in the deep dermis. Intravenous acyclovir was stopped, and intravenous voriconazole (200 mg twice daily) was added. Skin lesions gradually subsided and healed (Fig. 1d–f), and blood culture became negative. Her chest X-ray continued to improve, although residual shadows persisted (Fig. 2b). Peripheral blasts were cleared, with recovery of neutrophils and platelets. She * Yok-Lam Kwong [email protected]