Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults

Yasuyuki Arai; Tadakazu Kondo; Akio Shigematsu; Junji Tanaka; Kazuteru Ohashi; Takahiro Fukuda; Toshiro Kawakita; Takehiko Mori; Takumi Hoshino; Makoto Onizuka; Yukiyasu Ozawa; Shuro Yoshida; Yasunori Ueda; Ishikazu Mizuno; Yoshiko Atsuta; Shuichi Mizuta; Japan Society for Haematopoietic Cell Transplantation

doi:10.1111/bjh.14652

Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults

Br J Haematol. 2017 Jul;178(1):106-111. doi: 10.1111/bjh.14652. Epub 2017 Apr 25.

Authors

Yasuyuki Arai^{1

2}, Tadakazu Kondo¹, Akio Shigematsu³, Junji Tanaka⁴, Kazuteru Ohashi⁵, Takahiro Fukuda⁶, Toshiro Kawakita⁷, Takehiko Mori⁸, Takumi Hoshino⁹, Makoto Onizuka¹⁰, Yukiyasu Ozawa¹¹, Shuro Yoshida¹², Yasunori Ueda¹³, Ishikazu Mizuno¹⁴, Yoshiko Atsuta^{15

16}, Shuichi Mizuta¹⁷; Japan Society for Haematopoietic Cell Transplantation

Affiliations

¹ Department of Haematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Laboratory of Host Defences, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
³ Department of Haematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
⁴ Department of Haematology, Tokyo Women's Medical University, Tokyo, Japan.
⁵ Haematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital, Tokyo, Japan.
⁶ Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital, Tokyo, Japan.
⁷ Department of Haematology, National Hospital Organization Kumamoto Medical Centre, Kumamoto, Japan.
⁸ Division of Haematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
⁹ Leukaemia Research Centre, Saiseikai Maebashi Hospital, Maebashi, Japan.
¹⁰ Department of Haematology/Oncology, Tokai University School of Medicine, Isehara, Japan.
¹¹ Department of Haematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
¹² Department of Haematology, Hamanomachi Hospital, Fukuoka, Japan.
¹³ Department of Haematology/Oncology and Transfusion and Haemapheresis Centre, Kurashiki Central Hospital, Kurashiki, Japan.
¹⁴ Department of Haematology, Hyogo Cancer Centre, Akashi, Japan.
¹⁵ Japanese Data Centre for Haematopoietic Cell Transplantation, Nagoya, Japan.
¹⁶ Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁷ Department of Haematology, National Hospital Organization Toyohashi Medical Centre, Toyohashi, Japan.

PMID: 28439877
DOI: 10.1111/bjh.14652

Abstract

The efficacy of high-dose cytarabine (HDCA) plus cyclophosphamide/total-body irradiation (CY/TBI) has been proved in cord blood transplantation (CBT) for acute lymphoblastic leukaemia (ALL), but not in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT). In this cohort study, we compared the prognosis of CY/TBI (N = 1244) and HDCA/CY/TBI (N = 316) regimens in BMT/PBSCT for ALL. The addition of HDCA decreased post-transplant relapse, while significantly increasing non-relapse mortality (risk ratio, 1·33), and overall survival was not improved. The positive effects of HDCA reported in CBT cannot be extrapolated to BMT/PBSCT, and HDCA may not be recommended in these procedures.

Keywords: BMT/PBSCT; acute lymphoblastic leukaemia; allogeneic transplantation; conditioning regimens; high-dose cytarabine.

Publication types

Comparative Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Bone Marrow Transplantation / adverse effects
Bone Marrow Transplantation / methods*
Combined Modality Therapy
Cyclophosphamide / administration & dosage
Cyclophosphamide / adverse effects
Cytarabine / administration & dosage
Cytarabine / adverse effects*
Female
Humans
Japan / epidemiology
Kaplan-Meier Estimate
Male
Middle Aged
Peripheral Blood Stem Cell Transplantation / adverse effects
Peripheral Blood Stem Cell Transplantation / methods*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
Prognosis
Recurrence
Registries
Transplantation Conditioning / adverse effects
Transplantation Conditioning / methods*
Whole-Body Irradiation
Young Adult

Substances

Cytarabine
Cyclophosphamide