Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan

Takaaki Konuma; Satoshi Takahashi; Naoyuki Uchida; Yachiyo Kuwatsuka; Satoshi Yamasaki; Jun Aoki; Yasushi Onishi; Nobuyuki Aotsuka; Kazuteru Ohashi; Takehiko Mori; Masayoshi Masuko; Hirohisa Nakamae; Kouichi Miyamura; Koji Kato; Yoshiko Atsuta; Seiko Kato; Shigetaka Asano; Akiyoshi Takami; Yasushi Miyazaki; Adult Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

doi:10.1016/j.bbmt.2015.05.009

Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan

Biol Blood Marrow Transplant. 2015 Sep;21(9):1632-40. doi: 10.1016/j.bbmt.2015.05.009. Epub 2015 May 16.

Authors

Takaaki Konuma¹, Satoshi Takahashi², Naoyuki Uchida³, Yachiyo Kuwatsuka⁴, Satoshi Yamasaki⁵, Jun Aoki⁶, Yasushi Onishi⁷, Nobuyuki Aotsuka⁸, Kazuteru Ohashi⁹, Takehiko Mori¹⁰, Masayoshi Masuko¹¹, Hirohisa Nakamae¹², Kouichi Miyamura¹³, Koji Kato¹⁴, Yoshiko Atsuta¹⁵, Seiko Kato¹⁶, Shigetaka Asano¹⁷, Akiyoshi Takami¹⁸, Yasushi Miyazaki¹⁹; Adult Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Affiliations

¹ Department of Hematology and Oncology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan. Electronic address: [email protected].
² Division of Molecular Therapy, The Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
³ Department of Hematology, Toranomon Hospital, Tokyo, Japan.
⁴ Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
⁵ Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
⁶ Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
⁷ Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan.
⁸ Division of Hematology-Oncology, Japanese Red Cross Society Narita Hospital, Narita, Japan.
⁹ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁰ Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
¹¹ Division of Stem Cell Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan.
¹² Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
¹³ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
¹⁴ Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
¹⁵ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Department of Hematology and Oncology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
¹⁷ System Medical Biology Laboratory, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
¹⁸ Division of Hematology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan.
¹⁹ Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

PMID: 25985920
DOI: 10.1016/j.bbmt.2015.05.009

Abstract

Granulocyte colony-stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF-combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) ≥ 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI ≥ 8 Gy + Ara-C + CY (n = 119), TBI ≥ 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI ≥ 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF-combined conditioning regimen provides better engraftment and survival results in CBT for adults with MDS and sAML.

Keywords: Conditioning regimen; Cord blood transplantation; Granulocyte colony–stimulating factor; Myelodysplastic syndrome; Secondary acute myeloid leukemia.

Publication types

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

MeSH terms

Adolescent
Adult
Allografts
Cord Blood Stem Cell Transplantation*
Disease-Free Survival
Female
Granulocyte Colony-Stimulating Factor / administration & dosage*
Humans
Leukemia, Myeloid, Acute* / mortality
Leukemia, Myeloid, Acute* / therapy
Male
Middle Aged
Myelodysplastic Syndromes* / mortality
Myelodysplastic Syndromes* / therapy
Retrospective Studies
Survival Rate
Transplantation Conditioning / methods*

Substances

Granulocyte Colony-Stimulating Factor