title: Residual disease detected by multidimensional flow cytometry shows prognostic significance in childhood acute myeloid leukemia with intermediate cytogenetics and negative FLT3-ITD: a report from the Tokyo Children's Cancer Study Group.
abstract: Residual disease (RD) after induction chemotherapy may predict clinical outcome in acute myeloid leukemia (AML). In the present study, we investigated the prognostic significance of RD detected by multidimensional flow cytometry (MDF) among 34 children treated for AML in a clinical trial (JPLSG AML-05) in Japan. Bone marrow samples were analyzed at the points of the end of the first induction course (BMA-1) and second induction course (BMA-2) by MDF. RD was evaluated by detecting the immature cells showing abnormal antigen expression pattern; CD34(+), CD15(+), CD7(+). Thirteen (39.4 %) of 34 patients at BMA-1 and 8 (27.6 %) of 34 at BMA-2 had RD levels ≥0.1 %. There was no significant difference in 3y-EFS and 3y-OS between patients with RD levels ≥0.1 % and those with RD levels <0.1 % (53.8 versus 70.0 %, P = 0.30 and 50.0 versus 66.7 %, P = 0.27, respectively). However, IR cytogenetics and negative FLT3-ITD patients with RD levels ≥0.1 % exhibited significantly lower 3y-EFS and 3y-OS than those with RD levels <0.1 % (33.3 versus 83.3 %, P = 0.02 and 20.0 versus 76.9 %, P = 0.005, respectively). Our study suggests that RD shows prognostic relevance in pediatric patients with IR cytogenetics and negative FLT3-ITD AML.
authors.affiliation: Department of Pediatrics, St.Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan. d2keino@marianna-u.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Keino
authors.affiliation: Department of Pediatrics, St.Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Division of Leukemia and Lymphoma, Childern's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Department of Pediatrics, Toho University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan.
authors.forename: Kohmei
authors.initials: K
authors.lastname: Ida
authors.affiliation: Department of Pediatrics, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Pediatrics, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Setsuo
authors.initials: S
authors.lastname: Ota
authors.affiliation: Department of Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimura
authors.affiliation: Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yuza
authors.affiliation: Division of Leukemia and Lymphoma, Childern's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyotani
authors.affiliation: Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Division of Leukemia and Lymphoma, Childern's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Osumi
authors.affiliation: Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Division of Stem Cell Processing, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Mochizuki
authors.affiliation: Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Isoyama
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.affiliation: Department of Pediatrics, National Hospital Organization Osaka Medical Center, Osaka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.affiliation: ReproCELL Incorporated, Yokohama, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Toguchi
authors.affiliation: Department of Pediatrics, Toho University, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D020440:Gene Duplication; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; Children; FLT3-ITD; Multidimensional flow cytometry; Residual disease