title: Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy.
abstract: Cord blood transplantation (CBT) is an effective therapeutic option for adults with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen, but posttransplant relapse is still of high importance. High-dose cytarabine (HDCA) can be added to CY/TBI for an intensified regimen; however, its additional effects have not yet been completely elucidated. Therefore, we conducted a cohort study to compare the prognosis of HDCA/CY/TBI (n = 617) and CY/TBI (n = 312) in CBT for AML/MDS, using a Japanese transplant registry database. The median age was 40 years, and 86.2% of the patients had AML; high-risk disease was observed in 56.2% of the patients. The median follow-up period after CBT was approximately 3.5 years. Overall survival was significantly superior in the HDCA/CY/TBI group (adjusted hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.45-0.69; P < .01), and tumor-related mortality was lower (HR, 0.50; P < .01). The incidence of grade II to IV acute graft-vs-host disease (aGVHD) and chronic GVHD was significantly higher in the HDCA/CY/TBI group (HR, 1.33 and 2.30, respectively), but not grade III to IV aGVHD. Incidence of infectious episodes showed no significant difference. Nonrelapse mortality was not increased by the addition of HDCA. Higher-dose CA (12 rather than 8 g/m(2)) was more effective, particularly in patients at high-risk for disease. This study is the first to show the superiority of HDCA/CY/TBI to CY/TBI in CBT for AML/MDS. A large-scale prospective study is warranted to establish new conditioning regimens including HDCA administration.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan;
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan;
authors.forename: June
authors.initials: J
authors.lastname: Takeda
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan;
authors.forename: Kazunari
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan;
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan;
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan;
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Division of Hematology-Oncology, Japanese Red Cross Society Narita Hospital, Narita, Japan;
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Aotsuka
authors.affiliation: Department of Transfusion Medicine, Tokyo Metropolitan Tama Medical Center, Tama, Japan;
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kouzai
authors.affiliation: Department of Hematology, Osaka City University Hospital, Osaka, Japan;
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.affiliation: Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan;
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ota
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan;
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
authors.affiliation: Department of Hematology, Nippon Medical School Hospital, Tokyo, Japan;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan;
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan; and.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Department of Internal Medicine Division of Hematology, Aichi Medical University, Nagakute, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide