A 12-year-old boy a known case of relapsed AML has been admitted with impression of febrile neutropenia after the last course of chemotherapy on 16 April 2016. He received the FLAI regimen including fludarabine, cytarabine, and idarubicin (FLAI). After full sepsis workup, meropenem was started and cotrimoxazole (TMP/SMX) was continued with prophylaxis dosage (200 mg/12 hours by oral route). He received voriconazole as a fungal prophylaxis because of the previous history of proven pulmonary aspergillosis. Total white blood cell count was 200/mm3 (without countable neutrophils), hemoglobin was 10 g/dl, and platelet was 6000/mm3. First blood culture was positive for viridans streptococcus (by BACTEC system, time to detection: 9 hours) which was sensitive to vancomycin. Because high-grade fever continued after 48 hours of treatment and according to blood culture results, systemic vancomycin was added to antibacterial medications. The patient developed acute visual loss on 6th day of admission despite the appropriate type and dose of antibiotics. The neurological exam was normal. Retinal detachment and cancer associated retinopathy have been suggested as differential diagnoses in the first general ophthalmologist examination. The therapeutic dose of liposomal amphotericin B has been replaced with voriconazole.
Because high-grade fever was not resolved in 8th day of therapy (24 April), the blood sample was sent for a new culture, polymerase chain reaction (PCR; for aspergillosis, mucormycosis, candida, CMV, and tuberculosis), and enzyme-linked immunosorbent assay (ELIZA; for toxoplasmosis and cytomegalovirus antibody assay). A new chest X-ray has also been requested which revealed no new findings.
According to the results, toxoplasmosis IgM level was negative (0.1 IU/ml) and IgG level was at a borderline level (9.8 IU/ml). CMV blood PCR was reported to be 950  copy/mL. Anti-CMV antibody (IgG) was positive. Repeated blood PCR was negative for other fungal or viral pathogens.
Due to poor patient condition, spiral chest CT scan was requested on 10th day of admission with normal result. Rifampin has been added to the treatment regimen due to deteriorating patient's condition to achieve additive anti-Gram-positive synergistic effect. As the new blood culture results again revealed viridans streptococcus, which is susceptible to linezolid, linezolid has thus been replaced with vancomycin because of persistent bacteremia on 12th day of admission.
Lumbar puncture was performed on 29 April with total cells of 50/mm3 (white blood cells, 40/mm3 (polymorphonuclear leukocytes, 40%); red blood cells, 10/mm3), glucose of 50 mg/dl, protein of 48 mg/dl, and lactate dehydrogenase of 40 IU/L. Cytology report of cerebrospinal fluid (CSF) was positive for blasts, and PCR was negative for all viral and fungal suspicious agents.
Along with the patient's general condition, the patient complained of deteriorated visual function in the right eye. Therefore, a second ophthalmologist consult with a vitreoretinal specialist has been performed on 16th day of admission. The consultant ophthalmologist reported fluffy lesions with diffuse retinal hemorrhage and patchy focal necrosis (brush fire pattern) in the right eye and normal left eye (Figure 1). Thus, with first impression of cytomegalovirus (CMV) retinitis, vitreous aspiration was performed under anesthesia, and the sample was sent to the laboratory for PCR analysis. DNA was extracted from 100 microL ocular fluid by using High Pure Viral Nucleic Acid Kit (Roche Diagnostic GmbH, Germany) according to the instruction manual. Cytomegalovirus viral load was determined using a genesig quantitative real-time PCR kit (Primer Design Ltd. TM, Advanced Kit, United Kingdom) according to the manufacturer's instruction. The target sequence (glycoprotein B) has previously been shown to be a good genetic marker for CMV in other real-time PCR-based studies. This quantitative PCR assay was sensitive enough to detect 10 copies of CMV genomic DNA. Real-time PCR was performed using an ABI Step One Plus System (Applied Biosystems, Foster City, CA) with standard reagents (TaqMan Gene Expression Master Mix, Applied Biosystems, UK), which showed positive results for CMV (5000 copy/ml). Upon confirmation, the patient received 2 intravitreal injections of ganciclovir 1 week apart with adjunctive systemic antiviral therapy with ganciclovir 5 mg/kg twice daily on 24th day of admission for 2 weeks as induction. In addition, our plan was to continue for about 4 weeks.
On 34th day after admission, a new blood sample was requested for CMV PCR, which was shown 1150 copy/ml of CMV DNA in plasma without significant change in baseline CMV viral load.
Because of severe retinal necrosis and hole formation at some retinal areas, barrier argon laser photocoagulation was suggested and performed by the responsible ophthalmologist. The final blood culture became negative, but finally he was died due to refractoriness of leukemia and poor response to chemotherapy 8 weeks after admission.