Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis

Shuhei Kurosawa; Yoshimitsu Shimomura; Hidehiro Itonaga; Yuho Najima; Takeshi Kobayashi; Yukiyasu Ozawa; Yoshinobu Kanda; Shinichi Kako; Toshiro Kawakita; Ken-Ichi Matsuoka; Yumiko Maruyama; Shuichi Ota; Hideyuki Nakazawa; Kazunori Imada; Junya Kanda; Takahiro Fukuda; Yoshiko Atsuta; Jun Aoki

doi:10.1038/s41409-021-01447-y

Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis

Bone Marrow Transplant. 2021 Dec;56(12):3008-3015. doi: 10.1038/s41409-021-01447-y. Epub 2021 Sep 7.

Authors

Shuhei Kurosawa¹, Yoshimitsu Shimomura², Hidehiro Itonaga³, Yuho Najima⁴, Takeshi Kobayashi⁴, Yukiyasu Ozawa⁵, Yoshinobu Kanda⁶, Shinichi Kako⁷, Toshiro Kawakita⁸, Ken-Ichi Matsuoka⁹, Yumiko Maruyama¹⁰, Shuichi Ota¹¹, Hideyuki Nakazawa¹², Kazunori Imada¹³, Junya Kanda¹⁴, Takahiro Fukuda¹⁵, Yoshiko Atsuta^{16

17}, Jun Aoki¹⁵

Affiliations

¹ Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [email protected].
² Department of Haematology, Kobe City Hospital Organization Kobe City Medical Centre General Hospital, Kobe, Japan.
³ Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
⁴ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
⁵ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
⁶ Division of Hematology, Jichi Medical University, Shimotsuke, Japan.
⁷ Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
⁸ Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
⁹ Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
¹⁰ Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan.
¹¹ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
¹² Department of Hematology, Shinshu University School of Medicine, Matsumoto, Japan.
¹³ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
¹⁴ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁵ Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
¹⁶ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
¹⁷ Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.

PMID: 34489555
DOI: 10.1038/s41409-021-01447-y

Abstract

Myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective for acute myeloid leukemia. However, the effectiveness of Flu/Bu4 for myelodysplastic syndrome (MDS) remains poorly understood. Therefore, we retrospectively analyzed nationwide registry data in Japan from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu4 and busulfan/cyclophosphamide (Bu4/Cy) using propensity score (PS) matching. The primary endpoint was overall survival (OS). Among 2,482 MDS patients, 153 patients were assigned each to the Flu/Bu4 and Bu4/Cy groups. The 3-year OS rates were 52.7% (95% confidence interval [CI], 43.8-60.8%) and 49.5% (95% CI, 40.8-57.6%) in the Flu/Bu4 and Bu4/Cy group, respectively (P = 0.548). The 3-year progression-free survival (P = 0.858), the cumulative incidence of relapse (P = 0.536), and cumulative incidence of non-relapse mortality (P = 0.684) were not significantly different between the two groups. According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens. In conclusion, although our PS-matched cohort mainly comprised older patients who had a low hematopoietic cell transplantation-comorbidity index and low-risk disease status, Flu/Bu4 could be an alternative to Bu4/Cy for MDS patients prior to allo-HSCT.

MeSH terms

Busulfan / therapeutic use
Cyclophosphamide / therapeutic use
Graft vs Host Disease*
Hematopoietic Stem Cell Transplantation*
Humans
Leukemia, Myeloid, Acute* / therapy
Myelodysplastic Syndromes* / therapy
Propensity Score
Retrospective Studies
Transplantation Conditioning
Vidarabine / analogs & derivatives
Vidarabine / therapeutic use

Substances

Cyclophosphamide
Vidarabine
Busulfan
fludarabine