Dasatinib-associated reversible demyelinating peripheral polyneuropathy in a case of chronic myeloid leukemia

Int J Hematol. 2018 Mar;107(3):373-377. doi: 10.1007/s12185-017-2339-5. Epub 2017 Oct 13.

Abstract

Tyrosine kinase inhibitors (TKIs) are essential for the treatment of chronic myeloid leukemia (CML). Adverse effects of dasatinib have been reported; however, few reports have highlighted the association between dasatinib and demyelinating peripheral neuropathy (DPN). We report a patient with CML who developed acute onset of DPN associated with dasatinib therapy. A 46-year-old Japanese woman was treated with dasatinib for 7 months after the diagnosis of CML and she achieved a major molecular response (MMR). However, dysphagia, hoarseness, and muscle weakness progressively developed over 2 weeks. Nerve conduction studies revealed extensive demyelinating changes. Dasatinib was discontinued and the patient received intravenous immunoglobulin (IVIg), resulting in resolution of the symptoms. However, 1 month after the re-initiation of dasatinib therapy, muscle weakness developed again, indicating possible involvement of dasatinib in the development of DPN. She was then treated with IVIg, followed by prednisolone and nilotinib instead of dasatinib. These treatments eventually led to improvements of the symptoms and helped her achieve an MMR. This case suggests that dasatinib may carry risks of DPN possibly through immune-mediated disorders. It is clinically important to realize that dasatinib can cause extensive DPN, and a quick discontinuation and a switch to another TKI may be indicated.

Keywords: Chronic myeloid leukemia; Dasatinib; Demyelinating peripheral neuropathy; Guillain–Barre syndrome.

Publication types

  • Case Reports

MeSH terms

  • Acute Disease
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Dasatinib / adverse effects*
  • Dasatinib / therapeutic use
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / therapy
  • Drug Substitution
  • Female
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / therapy
  • Polyneuropathies / chemically induced*
  • Polyneuropathies / therapy
  • Prednisolone / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / administration & dosage
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Immunoglobulins, Intravenous
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Prednisolone
  • nilotinib
  • Dasatinib