Hyperviscosity Syndrome Induced Bilateral Visual and Auditory Impairment in Therapy Resistant Waldenström Macroglobulinemia with MYD88 and CXCR4 Mutations

Abstract

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib + dexamethasone (RVD). Bruton’s tyrosine kinase inhibitors could not be used initially due to ongoing lower gastrointestinal bleeding. She required five total sessions of plasma exchange and was finally initiated on zanubrutinib, achieving a partial response. She also received intravitreal bevacizumab with rapid resolution of the retinal hemorrhages but with little improvement of the SMD. She had partial restoration of her hearing in the right ear and only slight improvement in her bilateral visual deficits. The management of HVS in frail, elderly patients with therapy-resistant WM can be challenging. In these cases, plasma exchange is required until an effective systemic therapy can be safely instituted. Genomic profiling is important in the management of WM as it can predict treatment resistance and guide therapeutic decisions.

Keywords:

• hyperviscosity syndrome
• Waldenström macroglobulinemia
• central retinal vein occlusion
• exudative maculopathy
• serous macular detachment
• cochlear hemorrhage
• plasma exchange
• genomic sequencing
• CXCR4

Abbreviations

B2M, beta-2-microglobulin; BR, bendamustine + rituximab; BTKi, Bruton’s tyrosine kinase inhibitor; CRVO, central retinal vein occlusion; cpoise, centipoise; FA, Fluorescein angiography; FISH, fluorescence in situ hybridization; FLC, free light chains; HVS, hyperviscosity syndrome; IF, immunofixation; IgM, immunoglobulin M; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; OCT, optical coherence tomography; OD, right eye; OS, left eye; PCR, polymerase chain reaction; R, rituximab; RVD, rituximab, bortezomib, dexamethasone; SMD, serous macular detachment; SPEP, serum protein electrophoresis; WM, Waldenström Macroglobulinemia.

Consent for Publication

The study participant has given written informed consent to participate as well as consent to publish her data and images. IRB approval was not required to publish the case details.

Acknowledgment

The abstract of this paper was presented virtually at the International Summit on Hematology and Blood Disorders as a poster presentation with interim findings. The poster’s abstract is available online at: https://magnusconferences.com/hematology-blood/program/scientific-program/2023/hyperviscosit-syndrome-induced-bilateral-visual-and-auditory-impairment-in-cxcr4-mutant-waldenstrom-macroglobulinemia.

Disclosure

The authors report no conflicts of interest in this work.