Novel Insights into Pediatric Acute Lymphoblastic Leukemia Ophthalmic Relapses from a Nationwide Cohort Study

Abstract

Ten to fifteen percent of children with acute lymphoblastic leukemia (ALL) relapse following treatment. Of these, less than 2% display ophthalmic relapses, which owing to their scarcity, are largely undocumented, leaving clinicians with few diagnostic and therapeutic recommendations, despite serious functional sequelae. We conducted a French multicenter retrospective study to collect all clinical, radiological, biological, and therapeutic data, and outcomes for children with ALL ophthalmic relapses. From 2000 to 2020, 20 ophthalmic relapses occurring after first-line therapy performed before January 1^st, 2017 were included in our study: 14 B-ALL and 6 T-ALL. Fifteen patients (75%) had concomitant involvement of the central nervous system, and 11 (55%) a combined bone marrow relapse. Only 1 had an isolated ophthalmic relapse. Eight children (40%) died, 7 from a refractory disease and 1 from toxic death, and 4 patients relapsed. With a median follow-up of 63.1 months, 8 patients are currently alive in continuous complete remission with only 2 displaying severe ophthalmic sequelae. Although rare, ophthalmic relapse could have a significant impact on the functional prognosis of survivors. Their management must be multidisciplinary, with a central role given to ophthalmologists.

Keywords: ALL; Childhood; ophthalmic relapse.

Figure 1

Initial images of BCP-ALL ophthalmic relapse for a child with normal brain imaging and no blast at CSF. This figure reveals a sub-macular choroidal hypertrophy and choroidal infiltration above the optic nerve. a. Fundus retinography: choroidal infiltration above optic nerve; all big papillary vessels and papilla are hidden by the choroidal infiltration, blue triangle = macula. b. B-ultrasonography: C1 = infiltration above optic nerve; red cross = optic nerve; yellow circle = vitreous cavity. c. left picture: fundus retinography; green arrow = horizontal line of OCT. Right picture: horizontal OCT: yellow line = sub-macular choroidal hypertrophy; blue circle = choroid, orange circle = retina; yellow circle = vitreous cavity, blue triangle = macula. Legend: ALL: acute lymphoblastic leukemia; CSF: cerebrospinal fluid; OCT: optical coherence tomography.

Figure 2

Brain magnetic resonance imaging (MRI) of BCP-ALL ophthalmic relapse for a child with massive infiltration of the right optic nerve. Images show a major circumferential thickening of the homogeneous right optic nerve with little contrast with lesser involvement of the left optic nerve. A. Axial THRIVE sequences after gadolinium injection B. Coronal T2. Legend: ALL: acute lymphoblastic leukemia

Figure 3

Five years overall survival from initial ALL diagnosis according to the occurrence of early (n=11) versus late (n=9) ophthalmic relapse.