A 66-year-old female with no significant past medical history presented to her primary care physician for evaluation of progressive bilateral hearing loss. This was initially attributed to bilateral otitis media and sinusitis, and she was referred to an otolaryngologist for evaluation. Myringotomy tubes were placed without improvement in her symptoms. On re-evaluation, a tympanic membrane biopsy was performed which revealed involvement by a monotonous population of B-lymphocytes consistent with SLL/CLL. Immunohistochemical staining demonstrated a population of cells positive for CD20, CD5, and CD23 that were negative for CD10 and Cyclin D1. A complete blood count (CBC) at that time demonstrated a white blood cell count of 104,000/μL. Peripheral blood immunophenotyping was consistent with a diagnosis of chronic lymphocytic leukemia. Peripheral blood cytogenetic analysis was not performed. She initially was managed expectantly; however she developed worsening lymphocytosis and lymphadenopathy. Several months later she was treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). She completed 6 cycles of therapy with a partial response but noted marked improvement in her hearing. She experienced progression of her disease 3 months after stopping therapy and was treated with 4 doses of weekly rituximab which resulted in stable disease. At that time, she was referred to our institution for further management.
At the time of her initial visit, she was experiencing fatigue and worsening of her hearing loss. CBC showed a white blood count of 115,600/μ
L, a hemoglobin of 10.5
g/dL, and a platelet count of 348,000/μ
L. A review of a prior bone marrow biopsy confirmed the diagnosis of CLL and her peripheral blood cytogenetic profile demonstrated del(17p13.1) and del(13q34). The tympanic membrane biopsy was reviewed and involvement by CLL was confirmed (see ). A brain MRI showed bony and soft tissue enhancement along the skull base including the mandible, maxilla, and part of the calvarium with intracranial extension (see ). Cerebrospinal fluid (CSF) evaluation confirmed the presence of leptomeningeal disease. CT scans revealed generalized adenopathy including the bilateral axillae, mediastinum, celiac, retroperitoneal, and iliac regions, without hepatomegaly or splenomegaly.
Hematoxylin and eosin staining of the tympanic membrane, demonstrating infiltration with mature-appearing lymphocytes, consistent with involvement with CLL.
Magnetic resonance imaging of the brain demonstrating thickening of the skull base (a) that has responded to therapy and appears normal in subsequent imaging (b).
As she wished to defer chemotherapy, she was initiated on therapy with methyprednisolone (1
daily for 3 days) and rituximab (375
weekly for 12 weeks) as described by Castro et al. [4
]. In addition, she received intrathecal liposomal cytarabine, but her course was complicated by arachnoiditis requiring the intrathecal therapy to be held after three doses. At the conclusion of 12 weeks of systemic therapy, she achieved a partial response along with clearing of her CSF. She had an initial improvement of her symptoms, but within 3 months developed recurrent hearing loss associated with dizziness and imbalance. At this time, she was treated with cyclophosphamide, cladribine, and rituximab (CCR), given the central nervous system penetration of cladribine, as well as concurrent intrathecal liposomal cytarabine [5
]. She achieved only stable disease and remained symptomatic. She next was treated with HyperCVAD, and at the conclusion of 4 cycles she demonstrated marked improvement in her nodal disease and peripheral blood lymphocytosis. In addition, her CNS MRI abnormalities significantly improved (see ), as did her hearing loss and dizziness. She was evaluated for a reduced-intensity conditioning allogeneic transplant and her sister was found to be HLA identical. However, after consideration of options, she chose not to proceed with transplantation. She has remained off of treatment for 12 months without overt evidence of progression and without recurrence of her hearing loss.