Isolated Unilateral Optic Nerve Infiltration in Childhood Acute Lymphoblastic Leukemia

Isolated optic nerve involvement is rarely reported as an initial site of relapse after complete systemic remission of childhood acute lymphoblastic leukemia. In such cases, a full ophthalmologist exploration, radiologic investigations and a complete disease evaluation including cerebral spinal fluid and bone marrow studies with molecular evaluation of minimal residual disease have to be immediately performed for confirming the diagnosis of relapse and ensuing early treatment. The prognosis is usually poor and there is no consensus on the optimal management of such rare cases. More controversial is the treatment of patients with no detectable overt leukemia and suspected optic nerve leukemic infiltration. Central Testi et al. (2016) Email: JSM Clin Oncol Res 4(1): 1047 (2016) 2/4 the CR status, both morphologically and by flow cytometry. A funduscopy revealed tinge of the left edge of papilla; an orbit and brain magnetic resonance imaging (MRI) revealed no space occupying lesion or hydrocephalus; a left sided optic disc edema and peripapillary nerve fiber layer edema were detected. An electroretinogram test and visual evoked potentials were normal in both eyes; CSF was normal at morphologic and immunophenotypic studies and showed a normal blood brain barrier. BM was repeated and no disease was detected at molecular level (real-time quantitative polymerase chain reaction for T cell receptor. A few days later, because of the worsening of the visual acuity (VA), an orbit MRI was repeated and the left nerve edema proved unchanged but showed an increased perineural impregnation of contrast medium (Figure 1). BM and CSF examinations once again confirmed the CR status. CSF viral studies (CMV, EBV, HHV-6, HSV1, HSV2, VZV, BKV, JCV) were performed and proved negative. Based on the ophthalmologist’s suggestion, the patient received intravenous methylprednisolone (1 g/day). Two weeks later a MRI was repeated and documented an increase of left intra-orbital optic nerve perineural edema (4.2 mm vs 2.5 mm at the previous MRI). A fluorescein retinal angiography showed late fluorescence of left optic disc with blurring of its margins (Figure 2). Anti-edema treatment with dexamethasone and an osmotic diuretic was carried out; this was followed by a small reduction of the optic nerve perineural hyperintensity at MRI. Given the lack of clinical improvement and negativity of all hematologic studies, but suspecting isolated optic nerve disease recurrence, i.t. chemotherapy was administered without any success. CSF was negative; BM molecular study again confirmed the CR. Neuro-ophthalmologic examination described peripapillary edema with exudates and perivascular hemorrhages in the left eye, strongly suggestive to be secondary to infiltrative disease of the optic nerve meningeal sheaths. CSF examination was again negative for morphological, immunophenotypic, infectious studies and for galattomannan search. With a strong suspect of optic nerve leukemia recurrence, even without documented evidence of leukemic infiltration, the patient received high-dose chemotherapy (-cytarabine 3g/ m2/12 hours x 6 doses) with i.t cytarabine that preceded and followed systemic treatment. This strategy resulted in a slight VA improvement. This was confirmed at an optical coherence tomography (OCT) of the left optic nerve that showed a decreasing of the thickening and perimacular edema. One month later from beginning chemotherapy, the patient showed a worsening of the vision; a MRI revealed an increase thickness of the left optic nerve, while the CSF and BM continued to be negative for disease recurrence. Whole-brain radiotherapy was initiated and an improvement in VA was reported after the first few sessions. During radiation treatment, four months after the initial symptoms, the CSF revealed 73% of leukemic cells. A BM aspirate showed no evidence of leukemia. The patient received i.t. chemotherapy (methotrexate) and completed the planned radiotherapy. At the end of cranial radiation the CSF was clear but the BM showed 27% of leukemic cells with the same immunophenotypic profile of diagnosis. Systemic chemotherapy with cyclophosphamide, etoposide and nelarabine resulted in a perfect recovery of the left eye sight, Figure 1 Brain MRI Sequential magnetic resonance imaging showing enhancement along the left optic nerve. Central Testi et al. (2016) Email: JSM Clin Oncol Res 4(1): 1047 (2016) 3/4 but the patient failed to achieve a BM CR; he died ten months later, due to disease progression.