Bilateral optic nerve infiltration in pediatric ACUTE promyelocytic leukemia: A RARE and aggressive CNS relapse with probable ATRA resistance

Abstract Optic nerve leukemic infiltration is an exceptionally rare manifestation of acute promyelocytic leukemia (APL, AML-M3), especially in pediatric patients. We report the case of a child with a prior diagnosis of APL who initially achieved complete remission following standard induction with all-trans retinoic acid (ATRA), followed by consolidation and maintenance therapy. Two years post-treatment, the patient presented with progressive bilateral vision loss. Orbital magnetic resonance imaging revealed diffuse thickening and tortuous course of both optic nerves with intraneural hyperintensity on fat-suppressed sequences—radiological findings highly suggestive of leukemic infiltration. Bone marrow relapse was confirmed, along with CNS involvement based on cerebrospinal fluid (CSF) cytometry, leading to the diagnosis of combined medullary and CNS relapse. Reinduction therapy was initiated with ATRA, arsenic trioxide (ATO), and biweekly intrathecal chemotherapy. However, post-treatment assessments demonstrated persistent leukemic blasts in bone marrow and CSF, indicating treatment failure and raising strong suspicion of ATRA resistance. The patient's clinical condition continued to deteriorate despite therapeutic intensification. Given refractory disease and poor prognosis, transition to palliative care was made. The patient died shortly thereafter. This case highlights an unusual and severe form of CNS relapse in pediatric APL, manifesting as isolated bilateral optic nerve infiltration—a presentation that can mimic other neuro-ophthalmic disorders and delay diagnosis. It underscores the importance of early CNS imaging in APL patients with visual symptoms and the role of CSF evaluation even in the absence of systemic progression. Furthermore, it raises critical concerns regarding resistance to ATRA and the need for alternative therapeutic strategies in relapsed/refractory APL. For hematologists, this case serves as a poignant reminder of the challenges in managing sanctuary site relapses, the limitations of conventional therapy, and the need for vigilance in long-term follow-up of pediatric APL survivors. KEY WORDS: Arsenic Trioxide; Leukemia, Promyelocytic, Acute; Tretinoin