Refractory Tumorous and Neurodegenerative Histiocytosis Treated With Intra-Arterial Chemotherapy.

BACKGROUND AND OBJECTIVES: Histiocytoses are diverse hematopoietic diseases with disabling neurologic involvement. Recently, targeted mitogen-activated protein kinase pathway inhibitors have been used with clinical and radiologic response; however, some patients are unable to tolerate these treatments or have isolated and/or refractory neurologic, ocular, or head and neck (NOHN) disease. Intra-arterial administration of chemotherapy has conferred favorable responses in various neoplasms; however, treatment and outcomes across histiocytosis subtypes have not been examined. METHODS: Patients with biopsy-proven histiocytosis involving NOHN structures underwent an outpatient interventional procedure with angiography, selective catheterization, and intra-arterial infusion of melphalan, with target arteries depending on the site of disease. Patients were followed with radiologic (i.e., PET/CT, CT, MRI, or ophthalmic ultrasound and optical coherence tomography) and quantified functional assessments (i.e., vision, speech, or balance) as appropriate. Complete or partial radiologic and functional response rates were captured as well as frequency of subsequent progression. RESULTS: Eighteen patients underwent 74 total treatment instances. For 14 patients with radiologically evaluable tumorous disease, 10 (71%) had partial or complete response and the remaining 4 had stable disease; 3 of 14 (21%) had subsequent radiologic progression. Of 13 functionally evaluable patients, including 6 with neurodegenerative histiocytosis, 12 (92%) experienced functional improvement; 7 of 13 (54%) had subsequent functional worsening consistent with disease progression. There were no intraprocedural complications; 3 patients required hospitalization following treatment, including 1 patient with allergic reaction to melphalan. DISCUSSION: For patients with tumorous and neurodegenerative histiocytosis, intra-arterial melphalan represents a safe and highly effective treatment with potential to improve neurologic function. Additional study may clarify patients most suitable for this intervention. This novel treatment modality may represent a practice-changing innovation for refractory histiocytosis involving neurologic and ocular structures, as well as neurodegenerative forms. The treatment delivery form is novel, and future work should be directed at studying the efficacy of this modality to other forms of neurologic, ocular, head, and neck cancers. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with tumorous or neurodegenerative histiocytosis, selective angiographic catheterization and intra-arterial infusion of melphalan result in radiologic and functional improvement.