Clinical significance of high-dose cytarabine added to cyclophosphamide/total-body irradiation in bone marrow or peripheral blood stem cell transplantation for myeloid malignancy.
BACKGROUND
Addition of high-dose cytarabine (HDCA) to the conventional cyclophosphamide/total-body irradiation (CY/TBI) regimen significantly improved prognosis after cord blood transplantation (CBT) for adult acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The efficacy of HDCA in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), however, has not yet been elucidated.


RESULTS
We conducted a cohort study to compare the prognosis of HDCA/CY/TBI (N = 435) and CY/TBI (N = 1667) in BMT/PBSCT for AML/MDS using a Japanese transplant registry database. The median age was 38 years, and 86.0% of the patients had AML. Unrelated donors comprised 54.6%, and 63.9% of donors were human leukocyte antigen (HLA)-matched. Overall survival (OS) was not improved in the HDCA/CY/TBI group (adjusted hazard ratio (HR), 1.14; p = 0.13). Neutrophil engraftment was inferior (HR, 0.80; p < 0.01), and the incidence of hemorrhagic cystitis and thrombotic microangiopathy increased in HDCA/CY/TBI (HR, 1.47 and 1.60; p = 0.06 and 0.04, respectively), leading to significantly higher non-relapse mortality (NRM; HR, 1.48; p < 0.01). Post-transplant relapse and tumor-related mortality were not suppressed by the addition of HDCA.


CONCLUSIONS
This study indicated the inefficacy of HDCA/CY/TBI in BMT/PBSCT for AML/MDS. Our results should be validated in large-scale prospective studies.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. ysykrai@kuhp.kyoto-u.ac.jp.
Yasuyuki
Y
Arai
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. kaoki@kuhp.kyoto-u.ac.jp.
Kazunari
K
Aoki
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. water7@kuhp.kyoto-u.ac.jp.
June
J
Takeda
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. tadakazu@kuhp.kyoto-u.ac.jp.
Tadakazu
T
Kondo
Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan. eto-t@hamanomachi.jp.
Tetsuya
T
Eto
Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan. shuota@hokuyu-aoth.org.
Shuichi
S
Ota
Department of Hematology/Division of Stem Cell Transplantation, Kobe General Hospital/Institute of Biomedical Research and Innovation, Kobe, Japan. hhashimo@fbri.org.
Hisako
H
Hashimoto
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. tafukuda@ncc.go.jp.
Takahiro
T
Fukuda
Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. ozaway@nagoya-1st.jrc.or.jp.
Yukiyasu
Y
Ozawa
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. ycanda-tky@umin.ac.jp.
Yoshinobu
Y
Kanda
Department of Hematology, Meitetsu Hospital, Nagoya, Japan. katouc@meitetsu-hpt.jp.
Chiaki
C
Kato
Department of Cell Therapy and Transplantation Medicine, the University of Tokyo Hospital, Tokyo, Japan. kurokawa-tky@umin.ac.jp.
Mineo
M
Kurokawa
Department of Hematology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan. iwatok@hiroshima-med.jrc.or.jp.
Koji
K
Iwato
Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan. moni@is.icc.u-tokai.ac.jp.
Makoto
M
Onizuka
Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan. nohe@hiroshima-u.ac.jp.
Tatsuo
T
Ichinohe
Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan. y-atsuta@jdchct.or.jp.|Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan. y-atsuta@jdchct.or.jp.
Yoshiko
Y
Atsuta
Department of Internal Medicine Division of Hematology, Aichi Medical University, Nagakute, Japan. takami.akiyoshi.490@mail.aichi-med-u.ac.jp.
Akiyoshi
A
Takami
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use*; D003561:Cytarabine / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D011379:Prognosis; D055815:Young Adult
D003561:Cytarabine; D003520:Cyclophosphamide