A Relapsing Meningeal Acute Myeloid Leukaemia FLT3-ITD+ Responding to Gilteritinib

Chemotherapy. 2021;66(4):134-138. doi: 10.1159/000518356. Epub 2021 Aug 24.

Abstract

A patient with a therapy-related acute myeloid leukaemia (AML), NPM1mut, and FLT3-ITD+ was treated with induction and consolidation with CPX-351, obtaining a complete response (CR) but minimal residual disease persisted positive. Later, she complained progressive burning leg pain, weakening of the right hand and leg muscles, associated with absence of osteotendinous leg reflexes. Examination of cerebrospinal fluid (CSF) showed a meningeal relapse of AML. Moreover, a magnetic resonance imaging (MRI) showed 2 right meningeal implants of myeloid sarcoma and bone marrow revealed haematologic relapse of disease. She was treated with medicated lumbar punctures (LPs) followed by an FLA-Ida scheme, and she achieved a 2nd CR. Unfortunately, the patient developed hyperleucocytosis and reappearance of meningeal myeloid sarcoma at MRI. For this reason, a monotherapy with gilteritinib (an FLT3 inhibitor) was started: after 3 months of therapy, central nervous system (CNS)-disease shrunken and then faded, while AML in the bone marrow achieved only a partial response. This is the 1st report of a positive biological effect of gilteritinib on CNS (meningeal) myeloid sarcoma. There are no studies of gilteritinib concentration into CSF and penetration of gilteritinib into the blood-brain barrier should be further studied, given the paucity of drugs active on CNS relapse of AML. In patients receiving CPX-351 only, diagnostic LP should be considered after induction.

Keywords: Acute myeloid leukaemia; CPX-351; Central nervous system; Cerebrospinal fluid; Gilteritinib; Myeloid sarcoma.

Publication types

  • Case Reports

MeSH terms

  • Aniline Compounds / cerebrospinal fluid
  • Aniline Compounds / therapeutic use*
  • Bone Marrow / pathology
  • Brain / diagnostic imaging
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Magnetic Resonance Imaging
  • Mutation
  • Neoplasm Recurrence, Local
  • Protein Kinase Inhibitors / cerebrospinal fluid
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazines / cerebrospinal fluid
  • Pyrazines / therapeutic use*
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Aniline Compounds
  • Protein Kinase Inhibitors
  • Pyrazines
  • gilteritinib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3