Invisible Enemy: CMV Retinitis Despite Persistent Blood PCR Negativity in Pediatric AML

To the Editor, Cytomegalovirus(CMV) retinitis is a vision-threatening opportunistic infection in immunocompromised patients, particularly those with hematologic malignancies, transplantation, or AIDS (1,2).In hematologic malignancies,CMV reactivation is associated with intensive chemotherapy, corticosteroid exposure, and immune dysregulation (3).We report a 14-year-old boy with acute myeloid leukemia (AML) who developed CMV retinitis despite 17 consecutive negative peripheral blood CMV PCR results.The patient initially presented with prolonged fever, maculopapular rash, hepatosplenomegaly, and cytopenia and was diagnosed with hemophagocytic lymphohistiocytosis.Persistent fever and cytopenia led to referral to our center, where bone marrow examination established AML (FAB M5).He received AML-BFM therapy complicated by severe typhlitis, prolonged broad-spectrum antibiotics, and total parenteral nutrition.Low-level CMV DNAemia (133 IU/mL; IgM negative, IgG positive) was detected during follow-up,followed by persistently negative peripheral blood CMV PCR.On day 28, bone marrow showed morphological remission with negative minimal residual disease (<0.1%).After high-dose cytarabine+mitoxantrone (second induction cycle/block), he developed blurred vision in the left eye.Visual acuity was 20/20 in the right and 20/25 in the left eye.Slit-lamp examination showed 3+ anterior chamber cells, granulomatous gray-whitish keratic precipitates, and a thin fibrinous membrane at the pupillary margin (Figure 1A).CMV retinitis and leukemic intraocular infiltration were considered.Aqueous humor PCR detected CMV DNA (486,391 IU/mL), while blood PCR remained negative.Cytologic examination of the intraocular fluid was performed and was negative for malignant blast cells.Laboratory findings were WBC 3.70×10³/µL, ANC 2.72×10³/µL, ALC 0.43×10³/µL, Hb 8.6 g/dL, and platelets 305×10³/µL.Intravenous ganciclovir was initiated.On day 4, fundoscopy revealed a retinitis lesion approximately 1.5 optic disc diameters in the temporal peripheral retina (Figure 1B).Two intravitreal ganciclovir doses (2mg/0.05ml) and one foscarnet (2.4 mg/0.1 ml) dose were administered.Two weeks later, aqueous humor CMV DNA decreased to 28,601 IU/mL, while weekly blood PCR remained negative.By week 4, ocular inflammation had markedly regressed.However, a new adjacent focus of active retinitis developed despite partial regression of the initial lesion, prompting intravitreal foscarnet every 3-7 days until lesion control.The third chemotherapy cycle was completed with concomitant systemic ganciclovir and foscarnet.No further progression occurred and visual acuity was preserved.At last follow-up, visual acuity remained 20/20 bilaterally, inflammation had resolved, and retinal lesions had fully regressed with scarring(Figure 1C).The patient was not receiving systemic corticosteroids at the time of CMV retinitis onset.Similar cases of CMV retinitis have been reported in pediatric patients with hematological malignancies, although many had detectable peripheral CMV DNA or developed retinitis after transplantation (4-6).In contrast, our patient had only low-level CMV DNAemia (133 IU/mL) approximately two months before retinitis, followed by 17 consecutive negative blood CMV PCR results.Retinitis developed during lymphopenia, which may have impaired T-cell-mediated control u n c o r r e c t e d p r o o f of CMV (7).Sustained peripheral blood CMV PCR negativity does not exclude localized ocular CMV disease.Intravitreal antiviral therapy provides rapid local control (6), whereas systemic therapy may reduce the risk of contralateral and extraocular disease (7).High-risk patients with new visual symptoms should undergo prompt ophthalmologic examination, with intraocular fluid PCR testing when CMV retinitis is suspected, even if blood CMV PCR is negative.