Frequent occurrence of cytomegalovirus retinitis during immune reconstitution warrants regular ophthalmic screening in high-risk pediatric allogeneic hematopoietic stem cell transplant recipients.
BACKGROUND
Although cytomegalovirus (CMV) retinitis (CMVR) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT), standard operating procedures for ophthalmic monitoring are variable. In particular, authors perceived a greater risk of CMVR after pediatric HSCT for inherited immunodeficiencies, in patients who often have pretransplantation viremia. This study was therefore performed to identify high-risk pediatric HSCT recipients who would benefit from regular ophthalmic monitoring.


METHODS
During a 5-year study period, we retrospectively analyzed findings in 56 of 304 consecutive HSCT recipients (age range, 0.5-197 months) in whom significant CMV viremia developed (CMV level at PCR, ≥4000 copies/mL). All HSCT recipients with significant CMV viremia underwent retinal examination weekly (inpatients) or every other week (outpatients), with examinations performed by a skilled ophthalmologist.


RESULTS
CMVR developed in 13 (4%) of 304 HSCT recipients, 23% (13 of 56) of those with significant CMV viremia. Pretransplant viremia (odds ratio, 11.3; P < .01), acute (grade ≥2) graft-vs-host disease (odds ratio, 8.2; P < .02) and mismatched graft (odds ratio, 8; P < .02) were identified as independent risk factors. Compared with other invasive CMV diseases, CMVR was more often a late-onset disease, occurring at a median of 199 days after HSCT. At diagnosis, a significantly higher CD4 T-cell count (≥200/µL; P < .03) and a lower CMV load (P < .004) was observed in children with CMVR, compared with those in whom lung, gut, or liver CMV disease developed.


CONCLUSIONS
We report an increased risk of CMVR in high-risk pediatric HSCT recipients. This form of CMV disease differs from other invasive CMV disease in its relationship to immune reconstitution and viral dynamics. We have studied the relationship between these variables and suggested a risk-stratified ophthalmic screening strategy.
Molecular Immunology Unit Department of Blood and Marrow Transplantation.
Prashant
P
Hiwarkar
Department of Ophthalmology.
Eva
E
Gajdosova
Molecular Immunology Unit Department of Immunology, Great Ormond Street Hospital for Children, London.
Waseem
W
Qasim
Molecular Immunology Unit Department of Immunology, Great Ormond Street Hospital for Children, London.
Austen
A
Worth
Department of Virology.
Judith
J
Breuer
Department of Blood and Marrow Transplantation.
Robert
R
Chiesa
Centre for Pediatric Epidemiology and Biostatistics, Institute of Child Health, University College London.
Deborah
D
Ridout
Department of Ophthalmology.
Clive
C
Edelsten
Department of Ophthalmology.
Anthony
A
Moore
Molecular Immunology Unit Department of Blood and Marrow Transplantation.
Persis
P
Amrolia
Molecular Immunology Unit Department of Blood and Marrow Transplantation.
Paul
P
Veys
Department of Blood and Marrow Transplantation.
Kanchan
K
Rao
D000293:Adolescent; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D017726:Cytomegalovirus Retinitis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D009885:Ophthalmology; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects; D019562:Viral Load; D014766:Viremia / Q000453:epidemiology
CMV retinitis, paediatric HSCT; Cytomegalovirus (CMV); ophthalmic screening