Isolated Unilateral Optic Nerve Involvement as the Presenting Feature of Early Relapse in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Case Report

Ann Hematol Onco. 2024; 11(4): 1463.

Isolated Unilateral Optic Nerve Involvement as the Presenting Feature of Early Relapse in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Salman Alharbi¹*; Anne Tierens¹; Jonathan Micieli²; Dawn Maze¹

¹University of Toronto, Princess Margaret Cancer Center, Ontario, Canada

²University of Toronto, Toronto Western Hospital, Ontario, Canada

*Corresponding author: Salman Alharbi University of Toronto, Princess Margaret Cancer Center, Ontario, Canada. Email: salmanjh@hotmail.com

Received: September 16, 2024 Accepted: October 04, 2024 Published: October 11, 2024

Abstract

Central Mervous System involvement (CNS) in Acute Lymphoblastic Leukemia (ALL) can be present at initial diagnosis or at disease relapse and early detection is crucial for prompt intervention. Optic nerve infiltration by leukemic cells is an oncologic emergency that requires urgent therapy to spare vision along with systemic therapy, with limited data about the optimal therapeutic strategy. Isolated optic nerve Involvement at relapse is rare; described in Philadelphia chromosome negative (Ph-) ALL in 2.2% of relapses in children and exceeding rare in Philadelphia chromosome positive (Ph+) cases, particularly in the absence of systemic disease. Here we report isolated unilateral optic nerve involvement as the sole feature of early disease relapse in Ph+ ALL in the absence of systemic disease, leading to early detection of molecular relapse.

Keywords: Optic nerve; CNS; Acute lymphoblastic Leukemia; Dasatinib

Case Presentation

A 49-year-old female, initially presented to emergency with a 2 week history of bruising, epistaxis, and fever. Peripheral blood showed WBC 59 with 98% blasts, Platelet: 6, Hb 57. Her bone marrow was hypercellular and almost entirely replaced by blasts. Flow cytometry detected 86% CD34+ blasts which showed strong: CD10, CD19, CD20, CD22, CD34, CD38, CD58, CD66c, CD79a, HLA-DR, TdT, while Negative for: sCD3, cyCD3, CD7, MPO, TSLPR. Cytogenetics showed t(9;22) (q34.1;q11.2) while molecular testing confirmed BCR-ABL1 at p210 breakpoint. Diagnostic Lumbar puncture was negative for CNS involvement. She was induced with Dana Farber Cancer Institute (DFCI) chemotherapy protocol for age <60y (Ref), plus Imatinib at 400 mg. She achieved complete remission with negative MRD by flow cytometry, and her molecular testing showed 2.4 log reduction in BCR-ABL1 transcripts with lower limit of detection of 5.0 to 5.5 log reduction (0.0008 to 0.0003% IS). She completed maintenance phase of therapy while kept on Imatinib. Total of 12 intrathecal chemotherapy were received. She remained in remission over the whole treatment period with no evidence of disease relapse and her molecular MRD remained undetectable in her bone marrow. During follow up period, she was on concomitant treatment with ophthalmologist for myopia and glaucoma in addition to intraocular lens implantation for cataract with residual degree of vision impairment which remains stable. 3 years from initial diagnosis, she presented with gradually worsening loss of vision in her right eye with sensitivity to light over a period of 4 weeks, which was started after 10 days of undergoing LASER eye procedure for symptomatic high intraocular pressure following cataract surgery. CT brain was done and was unremarkable, followed by MRI which showed Enhancement and thickening of the right optic nerve, with optic nerve head protrusion, giving the differential of optic neuritis, which can be of infectious, inflammatory or Ischemic (Figure 1). She was evaluated by ophthalmology team and examination revealed impaired visual acuity with afferent pupillary defect of the right eye, with preservation of extraocular movements, while fundoscopic examination showed right optic disc edema with normal retina and macula. These findings supported the high suspicion of leukemic infiltration of the right optic nerve. The full neurological examination didn’t reveal any other significant findings, maintaining intact sensory function, motor power and normal reflexes. Her blood counts at that time showed WBC 3.6 with no peripheral blasts, Hb: 115, PLT: 169. A diagnostic lumbar puncture showed a clear CSF with no WBC by morphology. However, flow cytometry of the sample detects a very small B-cell precursor population consisting of approximately 0.9% of total cells with aberrant immunophenotype: Positive: CD10, CD19, CD38(dim), CD66c+123, CD73+304. While negative for CD20, (Figure 2). Such findings were supportive of involvement by the patient's previously diagnosed B-ALL. Bone Marrow Aspiration and biopsy showed morphological remission with <5% blasts with a very tiny population of CD19+ B-cell precursors with the aberrant immunophenotype are detected at 0.009% of total cells by flowcytometry which are CD10/19/20 heterogeneous/CD34/38(dim)/45(dim/66c+123). Molecular testing showed 2.4 log reduction of BCR/ABL1 transcripts indicating an early molecular relapse of the disease. ABL kinase domain mutation testing showed no clinically relevant variants.