Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy

AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)415-422
    Number of pages8
    JournalBlood
    Volume126
    Issue number3
    DOIs
    Publication statusPublished - Jul 16 2015

    Fingerprint

    Whole-Body Irradiation
    Cytarabine
    Fetal Blood
    Cyclophosphamide
    Dosimetry
    Blood
    Transplantation
    Irradiation
    Acute Myeloid Leukemia
    Myelodysplastic Syndromes
    Neoplasms
    Hazards
    Graft vs Host Disease
    Grafts
    Transplants
    Mortality
    Incidence
    Registries
    Tumors
    Cohort Studies

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

    Cite this

    AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation (2015). Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy. Blood, 126(3), 415-422. https://doi.org/10.1182/blood-2015-04-642652

    Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy. / AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation.

    In: Blood, Vol. 126, No. 3, 16.07.2015, p. 415-422.

    Research output: Contribution to journalArticle

    AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation 2015, 'Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy', Blood, vol. 126, no. 3, pp. 415-422. https://doi.org/10.1182/blood-2015-04-642652
    AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation. Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy. Blood. 2015 Jul 16;126(3):415-422. https://doi.org/10.1182/blood-2015-04-642652
    AML and MDS Working Group of the Japan Society for Hematopoietic Cell Transplantation. / Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy. In: Blood. 2015 ; Vol. 126, No. 3. pp. 415-422.
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    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.",
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    AU - Takeda, June

    AU - Aoki, Kazunari

    AU - Kondo, Tadakazu

    AU - Takahashi, Satoshi

    AU - Onishi, Yasushi

    AU - Ozawa, Yukiyasu

    AU - Aotsuka, Nobuyuki

    AU - Kouzai, Yasuji

    AU - Nakamae, Hirohisa

    AU - Ota, Shuichi

    AU - Nakaseko, Chiaki

    AU - Yamaguchi, Hiroki

    AU - Kato, Koji

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    N2 - 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.

    AB - 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.

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