title: Characteristics of patients with development of large granular lymphocyte expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation.
abstract: BACKGROUND
  Widespread use of tyrosine kinase inhibitors (TKIs) in combination with chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-SCT) has totally changed the existing treatment strategies for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). However, the prognosis after relapse after allo-SCT is still dismal.
  
  
  METHODS
  We analyzed the clinical outcome of therapy using dasatinib, a second-generation TKI, in 9 patients with relapsed Ph(+)ALL after allo-SCT. Dasatinib was initiated at a median time of 168 days after allo-SCT at dosages ranging from 20 mg to 100 mg daily.
  
  
  RESULTS
  Six of 9 patients manifested a marked increase in large granular lymphocytes (LGLs), but all 6 patients discontinued dasatinib because of adverse events (AEs) such as pleural effusion. Four of 6 patients resumed dasatinib, and 3 of them have been alive with molecular complete remission and a persistent increase of LGLs.
  
  
  CONCLUSIONS
  Our results demonstrated that dasatinib therapy can induce LGL expansion accompanied by AEs, but this phenomenon can be associated with long-term survival benefit in a proportion of relapsed Ph(+)ALL patients after allo-SCT.
authors.affiliation: Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan; Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. Electronic address: toshmiya@intmed1.med.kyushu-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kamimura
authors.affiliation: Department of Hematology, Japan Community Health care Organization Kyushu Hospital, Kitakyushu, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Hideho
authors.initials: H
authors.lastname: Henzan
authors.affiliation: Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Shiratsuchi
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
authors.affiliation: Department of Hematology, Japan Community Health care Organization Kyushu Hospital, Kitakyushu, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D000069439:Dasatinib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069439:Dasatinib
keywords: Adverse events; Allogeneic stem cell transplantation; Dasatinib; Large granular lymphocyte; Philadelphia-positive ALL