Cytomegalovirus Reactivation During Therapy for Pediatric Acute Lymphoblastic Leukemia

ABSTRACT Cytomegalovirus (CMV) reactivation is a recognized complication after hematopoietic stem cell transplantation, but its relevance during conventional chemotherapy for pediatric acute lymphoblastic leukemia (ALL) is poorly defined, especially in CMV‐prevalent regions. This retrospective cross‐sectional study was conducted at a tertiary pediatric oncology center in South India from January 2020 to August 2025. Children (≤ 18 years) with ALL who developed CMV reactivation during chemotherapy were included. CMV testing was performed based on clinical indications, and viral load was quantified using multiplex polymerase chain reaction. Demographic, clinical, laboratory, treatment, and outcome data were analyzed. Of 150 children treated for ALL, 29 (19.3%) experienced CMV reactivation. The median age was 6 years, with a male predominance (72.4%). Reactivation occurred predominantly during consolidation (51.7%) and maintenance (41.4%) phases. Fever was the most common presentation (75.9%). The median CMV viral load was 1.48 × 10 3 IU/mL; 69% had viral loads > 1 × 10 3 IU/mL. Lymphopenia (absolute lymphocyte count < 0.5 × 10 3 /mm 3 ) was observed in 62% of patients. The median time to CMV PCR negativity was 14 days, and peak viral load showed a strong positive correlation with time to PCR clearance ( ρ = 0.697, p < 0.001). Antiviral therapy was administered to 79.3% of patients. At last follow‐up, 86.2% were alive, with no CMV‐attributable mortality. CMV reactivation during chemotherapy for pediatric ALL is frequent in high‐prevalence settings and is associated with lymphopenia and prolonged immunosuppression. A targeted, risk‐adapted strategy for CMV testing and treatment may be preferable to universal surveillance.