title: [Refractory acute myeloid leukemia developed malignancy-associated hemophagocytic lymphohistiocytosis during treatment of invasive fungal infection].
abstract: We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.
authors.affiliation: Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki.
authors.forename: Ai
authors.initials: A
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moritake
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Shimonodan
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kojima
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kamimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020314:Central Nervous System Fungal Infections / Q000150:complications / Q000628:therapy*; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D008942:Mitoxantrone / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone