Guillain-Barre Syndrome Following Azacitidine for Treatment of Myelodysplastic Syndrome.

In this case report we describe a 65-year-old woman with myelodysplastic syndrome who was started on azacitidine and subsequently developed Guillain-Barre Syndrome (GBS). To our knowledge, there are no other reported cases of azacitidine-associated GBS.

This patient was diagnosed in 2004 when a bone marrow biopsy done for anemia showed erythroid, myeloid and megakaryocytic dysplasia. Cytogenetics were normal. Her baseline hemoglobin was 7g/dL. Despite combined growth factor support and thalidomide, this patient remained transfusion-dependent, requiring packed red blood cells (PRBCs) every 3 weeks. Her only other medical problem was well-controlled diabetes without renal impairment or neuropathy. Liver function was normal. Her medications included deferasirox, glyburide, metformin and pioglitazone. At baseline she had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0. This patient received a 7-day course of subcutaneous azacitidine, after which she required a total of 7 units PRBCs for grade 3 anemia. She did not experience any other complications such as viral illness or diarrheal infection. There were no changes in medications. Thirty-four days after starting azacitidine she experienced acute onset of bilateral lower extremity weakness starting distally and moving proximally. The next day she developed bilateral weakness in her distal upper extremities. On initial evaluation she was found to have symmetric bilateral upper and lower extremity weakness. Strength in the distal and proximal extremities (both upper and lower) was 1/5 and 3/5, respectively. Lower extremity deep tendon reflexes were absent. Sensation remained intact, and cranial nerve exam was normal with preserved respiratory muscle strength. A non-contrast head CT and cervical spine MRI without contrast were normal. CSF studies revealed elevated protein in the absence of cells. Lumbosacral MRI with contrast showed a non-specific, faint enhancement of the anterior lumbosacral nerve roots. An EMG indicated an acute demyelinating process. She was diagnosed with GBS and received a 5-day course of intravenous immunoglobulin with notable improvement in upper extremity strength within 1 week. At baseline after recovery from acute presentation, she was wheelchair-bound with an ECOG PS of 3.

This is the first reported case of azacitidine-associated GBS. Azacitidine is a DNA hypomethylating agent that was FDA-approved in 2004 for the treatment of myelodysplastic syndrome. A common side effect is grade 3-4 myelosuppression. The common non-hematologic side effects are nausea and vomiting. Severe adverse non-hematologic reactions to azacitidine are uncommon (Sullivan, et al, AJHP 2005;62:1567-73). In 1975 neuromuscular toxic syndrome was described in 17 leukemic patients after they received combination therapy containing azacitidine (Levi JA, Wiernik PH Cancer Chemother Rep 1975;59:1043-45). A case report in 1985 documented a child with acute rapidly reversible CNS toxicity (coma preceded by somnolence/myalgias) days after receiving an erroneously high dose of 5-azacytidine for acute leukemia (Weisman, et al, J Pediatr Hematol Oncol 1985;7:86-88). No other azacitidine-associated adverse neurologic events, and specifically no reports of a demyelinating process, have been published. While the association between GBS and certain infections and immunizations has been well documented (Hughes RA, Cornblath DR Lancet 2005;366:1653-66), there is data to suggest that GBS can be medication-induced. Zimeldine has been described as the probable link to the development of GBS in 10 patients (Fagius, et al, JNNP 1985;48:65-69). In our patient, the temporal relationship between starting treatment and the development of neurologic symptoms, along with the lack of other known GBS-inciting factors, form a strong basis for an associational relationship between azacitidine and the development of GBS. It is therefore important that clinicians are aware of this potential severe adverse effect.

No relevant conflicts of interest to declare.