First Case of Association between Autoimmune Autonomic Ganglionopathy (AAG) and Myeloproliferative Neoplasms (MPNs)

Abstract

IntroductionAutoimmune autonomic ganglionopathy (AAG) is a rare disease that presents with different autonomic symptoms and positive autoantibodies against the ganglionic acetylcholine receptor (gAChR) in 50 % of the cases. Eighty percent of seropositive patient has extra-autonomic manifestations. Extra-autonomic manifestations include sensory disturbance, central nervous system involvement, endocrine disorders autoimmune diseases, and cancers. It has been reported with various malignancies, such as small lung cancer, thymoma, ovarian tumors and others.MethodWe report a case from MD Anderson cancer center (MDACC) and to our knowledge it is first case in literature of a patient Autoimmune autonomic ganglionopathy associated with primary myelofibrosisResultA 55-year-old African American male diagnosed with JAK2 V617F positive primary myelofibrosis in 2005 and placed on observation until September 2012 when he was referred to MDACC for further management. He was started on protocol with Ruxolitinib + lenalidomide and did well initially, but during the course of treatment, he started to experience leg weakness. Initially in the left leg and then the right leg. lenalidomide was placed on hold and in April 2015, ruxolitinib was held as well. On examination he has left leg weakness in addition to weak hand grip on the same side.On Further evaluation, he was diagnosed with inclusion body myositis after muscle biopsy He was then lost to follow up and followed with outside hematologistIn February 2020, he developed cytopenias and was referred back to MDACC for management. He was seen and we performed a bone marrow shortly thereafter. He continued to have PMF, molecular, cytogenetics could not be performed on bone marrow due to dry tap. Patient started on “investigational agent. In early 2021 patient started to have orthostatic hypotension and syncope. Serum paraneoplastic antibody panel revealed acetylcholine Receptor Gang Neuronal Ab.The above finding along with his automimic symptoms consists with diagnosis of autoimmune autonomic ganglionopathy.ConclusionAutoimmune autonomic ganglionopathy (AAG) with extra-autonomic manifestations is a very rare and not well known. It is reported before to be associated with solid malignancy, we describe here first association with hematological malignancy which is primary myelofibrosis. We aim to add this to literature, and to increase the knowledge and awareness of both hematologists and neurologists about this association and possible other hematological malignancies may be reported in the future DisclosuresVerstovsek: Celgene: Consultancy, Research Funding; CTI BioPharma: Research Funding; Genentech: Research Funding; Promedior: Research Funding; PharmaEssentia: Research Funding; Ital Pharma: Research Funding; Protagonist Therapeutics: Research Funding; Roche: Research Funding; Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; NS Pharma: Research Funding; Blueprint Medicines Corp: Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy.