title: Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions.
abstract: A 23-year-old man with Philadelphia-chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his HLA-identical brother in first hematological remission following induction chemotherapy which included imatinib. He had no acute graft-versus-host disease (GVHD), and 4.5 months after HSCT, he had a molecular relapse (180,000 copies/mug RNA of minor bcr/abl transcripts (m-bcr/abl) without mutation in 22 sites including the p-loop region). Following discontinuation of cyclosporine A, imatinib (600 mg daily) was restarted and 4 days later donor lymphocyte infusion (DLI) (5 x 10(7)/kg of CD3(+) cells) was given. In 2 weeks, the marrow m-bcr/abl became undetectable. He received two further DLIs and imatinib was continued at a reduced dose of 400 mg a day. At the time of this report, he remains in complete hematological remission more than 33 months after allo-HSCT and persists in the second molecular remission for longer than 24 months. During this clinical course, he became positive for anti-nuclear antibody after second DLI, without any other manifestations of GVHD. The standard treatment for Ph(+) ALL relapsing after allo-HSCT still remains to be established. Imatinib in combination with DLI for early molecular relapse may be a promising option.
authors.affiliation: Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimitsu
authors.affiliation: Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, Shitsukawa, Toh-on, Ehime, 791-0295, Japan. yunarief@m.ehime-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ozaki
authors.affiliation: Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Kakushi
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Division of Host Response, Center for Chronic Viral Disease, Graduate School of Medical and Dental Science, Kagoshima University, Kagoshima, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Arima
authors.affiliation: Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
mesh_terms: D000328:Adult; D001549:Benzamides; D016572:Cyclosporine / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D019520:Living Donors; D017710:Lymphocyte Transfusion; D008297:Male; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D035781:Siblings; D014184:Transplantation, Homologous
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016572:Cyclosporine; D000068877:Imatinib Mesylate