title: Intrathecal donor lymphocyte infusion for isolated leukemia relapse in the central nervous system following allogeneic stem cell transplantation: a case report and literature review.
abstract: An 8-year-old boy with a bone marrow relapse of T cell acute lymphoblastic leukemia underwent stem-cell transplantation from a human leukocyte antigen (HLA)-haploidentical mother. Five months later, he relapsed with central nervous system (CNS) involvement. Systemic chemotherapy and repeated intrathecal chemotherapy induced consciousness disturbances and frequent arrhythmia, prompting us to discontinue the chemotherapy. He had already received an 18-Gy prophylactic cranial irradiation, an 8-Gy total body irradiation, and a 15-Gy local irradiation for pituitary gland involvement. We therefore performed five intrathecal donor lymphocyte infusions (IDLIs) in escalating doses from 1 × 10(4) up to 1 × 10(6) cells/kg. All IDLIs were safe without infusion reactions or graft-versus-host disease. After the second and later IDLIs, donor mononuclear cells were continuously detected in cerebrospinal fluid; however, he did not achieve donor-dominant chimerism. Based on our case and four cases reported in the literature, the efficacy of IDLI therapy is limited for CNS relapse of hematological malignancies. However, we suggest that IDLI remains a feasible and safe option, as no GVHD or other adverse effects occurred, even in the HLA-haploidentical setting. We will make further efforts to increase the efficacy.
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.|Division of Hematology/Oncology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Yanagisawa
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan. yxnakaza@shinshu-u.ac.jp.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.|Division of Hematology/Oncology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakashita
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.|Department of Pediatrics, School of Dentistry, Matsumoto Dental University, Shiojiri, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiohara
authors.affiliation: Division of Blood Transfusion, Shinshu University Hospital, Matsumoto, Japan.|Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Shimodaira
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D064591:Allografts; D001853:Bone Marrow; D016543:Central Nervous System Neoplasms / Q000628:therapy*; D002648:Child; D005260:Female; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007278:Injections, Spinal; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D009364:Neoplasm Recurrence, Local; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens
keywords: Acute lymphoblastic leukemia; CNS relapse; Donor lymphocyte infusion; Stem cell transplantation