Guillain Barre Syndrome: A rare neuro toxicity following All Trans Retinoic Acid and Arsenic Trioxide induction chemotherapy in a patient with Acute Promyelocytic leukemia

Introduction/Background/Significance: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy usually triggered by infections. Arsenic Trioxide (ATO) and All Trans retinoic acid (ATRA) are mainstays in the treatment of acute promyelocytic leukemia (APL). Both these agents have known potential to cause neurological side effects, most commonly self-limited neuropathy. We present a rare case of GBS developing during induction therapy in a patient undergoing treatment for APL.

Materials and Methods/Case Presentation/Objective: A 63-year- old male with a past medical history for obesity, Type 2 diabetes mellitus, recurrent non-human immunodeficiency virus (HIV)- human herpes virus 8(HHV-8) Kaposi sarcoma (KS) s/p treatment with systemic chemotherapy with doxil and paclitaxel 9 years prior to the current presentation was seen in the Oncology clinic. During his regular follow up complete blood count revealed pancytopenia hemoglobin of 9.8 g/dL, WBC- 600/mm³ and platelet -40,000/mm³. A bone marrow biopsy confirmed the diagnosis of acute promyelocytic leukemia.

He started induction chemotherapy with ATRA and ATO. He developed de differentiation syndrome shortly which was managed with dexamethasone and hydroxyurea. He received a total of 56 days of ATRA and 41 days of ATO and achieved complete molecular remission following the induction chemotherapy. His course was complicated by fluid overload, congestive heart failure and Pneumocystis jiroveci pneumonia. He received a total of 56 days of ATRA and 41 days of ATO and achieved complete molecular remission following the induction chemotherapy.

Prior to starting consolidation chemotherapy with ATO+ ATRA, he developed worsening neuropathy of his upper and lower extremities and increased difficulty to do activities of daily living. Of note his prior KS treatment was complicated by grade 2 peripheral neuropathy from his chemotherapy He was hospitalized following recurrent falls. Neurological evaluation demonstrated significant weakness in bilateral quadriceps, decreased sensation to temperature to the mid-calf areflexia in both ankles and knees raising concern for GBS was considered. An MRI brain and spine was unremarkable. A CSF study was done and showed CSF protein of 150 mg/dL. He was started on a 5-day course of IVIG 0.4g/kg. He had significant symptomatic improvement in 72 hours after starting his IVIG treatment and within 4 to 6 weeks was able to walk with a cane and in about 3 months he was walking without any support. He achieved MRD negative status following induction and was maintained on ATRA regimen 2 weeks on and 2 weeks off for next 5 months with concomitant 50% dose reduced ATO for 3 cycles. He has not had any worsening of his neurological functions after restarting chemotherapy. He has remained in complete molecular remission since then.

Results/Description/Main Outcome Measures: He has not had any worsening of his neurological functions after restarting chemotherapy. He has remained in complete molecular remission.

Conclusions: GBS should be recognized as a severe neurological complication of induction therapy for APL. Patients could receive low dose ATRA and ATO without neurological complication