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Peer-reviewedCC BYScientific Reports

Conditioning-adapted methotrexate in cord blood transplantation for high-risk acute myeloid leukemia: a nationwide Japanese cohort analysis

  • Satoshi Yamasaki1
  • Masamitsu Yanada2
  • Tomomi Toubai3
  • Kaito Harada4
  • Masatsugu Tanaka5
  • Makoto Onizuka4
  • Tetsuya Nishida6
  • Norimichi Hattori7
  • Toru Izumi8
  • Satoshi Takahashi9
  • Masashi Sawa10
  • Yuta Katayama11
10 more authors
  • Toshiro Kawakita12
  • Jun Ishikawa13
  • Masahito Tokunaga14
  • Koichi Onodera15
  • Koji Nagafuji16
  • Hideki Nakasone17
  • Fumihiko Ishimaru18
  • Junya Kanda19
  • Yoshiko Atsuta20
  • Takaaki Konuma9
20 affiliations
  1. 1Department of Hematology, St. Mary’s Hospital
  2. 2Department of Hematology and Oncology, Nagoya City University East Medical Center
  3. 3Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
  4. 4Department of Hematology and Oncology, Tokai University School of Medicine
  5. 5Department of Hematology, Kanagawa Cancer Center
  6. 6Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
  7. 7Division of Hematology, Department of Medicine, Showa Medical University School of Medicine
  8. 8Department of Hematology, National Hospital Organization Sendai Medical Center
  9. 9Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo
  10. 10Department of Hematology and Oncology, Anjo Kosei Hospital
  11. 11Department of Hematology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
  12. 12Department of Hematology, National Hospital Organization Kumamoto Medical Center
  13. 13Department of Hematology, Osaka International Cancer Institute
  14. 14Department of Hematology, Imamura General Hospital
  15. 15Department of Hematology, Tohoku University Hospital
  16. 16Division of Hematology and Oncology, Department of Medicine, Kurume University Hospital
  17. 17Division of Emerging Medicine for Integrated Therapeutics, Center for Molecular Medicine, Jichi Medical University
  18. 18Japanese Red Cross Blood Service Headquarters
  19. 19Department of Hematology, Graduate School of Medicine, Kyoto University
  20. 20Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine
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Abstract

Allogeneic cord blood transplantation (CBT) is a curative option for adults with high-risk acute myeloid leukemia, but outcomes depend on conditioning intensity and graft-versus-host disease (GVHD) prophylaxis. We analyzed 1311 adults undergoing first single-unit CBT with six protocol-defined myeloablative or reduced-intensity regimens and uniform calcineurin inhibitor plus short-course methotrexate (MTX) at high, standard, or low doses. Neutrophil engraftment was rapid (median 20 days) and similar across MTX dose categories. The 2-year overall and disease-free survival rates were 48.5% and 44.1%, and 1-year transplant-related mortality was 30.7%. Low-dose MTX was independently associated with more chronic GVHD and inferior chronic GVHD-free/relapse-free survival without reducing relapse in chemotherapy-based myeloablative and fludarabine-based reduced-intensity regimens. Regarding total-body-irradiation–based myeloablative regimens, more intensive MTX exposure was associated with lower rates of grade II–IV acute GVHD and improved GVHD-free/relapse-free survival compared with low-dose MTX. For chemotherapy-based myeloablative and fludarabine-based reduced-intensity regimens, standard-dose MTX generally provided the most favorable balance between GVHD control and survival. These nationwide data suggest that MTX exposure should be tailored to the conditioning backbone rather than uniformly reduced, and provide pragmatic, regimen-specific benchmarks to individualize GVHD prophylaxis and guide future prospective and international comparative studies of CBT for high-risk acute myeloid leukemia.

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Cite

BibTeXRIS
BibTeX
@article{yamasaki2026conditioningadapted,
  title = {{Conditioning-adapted methotrexate in cord blood transplantation for high-risk acute myeloid leukemia: a nationwide Japanese cohort analysis}},
  author = {Satoshi Yamasaki and Masamitsu Yanada and Tomomi Toubai and Kaito Harada and Masatsugu Tanaka and Makoto Onizuka and Tetsuya Nishida and Norimichi Hattori and Toru Izumi and Satoshi Takahashi and Masashi Sawa and Yuta Katayama and Toshiro Kawakita and Jun Ishikawa and Masahito Tokunaga and Koichi Onodera and Koji Nagafuji and Hideki Nakasone and Fumihiko Ishimaru and Junya Kanda and Yoshiko Atsuta and Takaaki Konuma},
  journal = {Scientific Reports},
  year = {2026},
  month = jul,
  doi = {10.1038/s41598-026-63050-9},
  url = {https://doi.org/10.1038/s41598-026-63050-9},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Conditioning-adapted methotrexate in cord blood transplantation for high-risk acute myeloid leukemia: a nationwide Japanese cohort analysis
AU  - Satoshi Yamasaki
AU  - Masamitsu Yanada
AU  - Tomomi Toubai
AU  - Kaito Harada
AU  - Masatsugu Tanaka
AU  - Makoto Onizuka
AU  - Tetsuya Nishida
AU  - Norimichi Hattori
AU  - Toru Izumi
AU  - Satoshi Takahashi
AU  - Masashi Sawa
AU  - Yuta Katayama
AU  - Toshiro Kawakita
AU  - Jun Ishikawa
AU  - Masahito Tokunaga
AU  - Koichi Onodera
AU  - Koji Nagafuji
AU  - Hideki Nakasone
AU  - Fumihiko Ishimaru
AU  - Junya Kanda
AU  - Yoshiko Atsuta
AU  - Takaaki Konuma
PY  - 2026
DA  - 2026/07/01
JO  - Scientific Reports
DO  - 10.1038/s41598-026-63050-9
UR  - https://doi.org/10.1038/s41598-026-63050-9
AB  - Allogeneic cord blood transplantation (CBT) is a curative option for adults with high-risk acute myeloid leukemia, but outcomes depend on conditioning intensity and graft-versus-host disease (GVHD) prophylaxis. We analyzed 1311 adults undergoing first single-unit CBT with six protocol-defined myeloablative or reduced-intensity regimens and uniform calcineurin inhibitor plus short-course methotrexate (MTX) at high, standard, or low doses. Neutrophil engraftment was rapid (median 20 days) and similar across MTX dose categories. The 2-year overall and disease-free survival rates were 48.5% and 44.1%, and 1-year transplant-related mortality was 30.7%. Low-dose MTX was independently associated with more chronic GVHD and inferior chronic GVHD-free/relapse-free survival without reducing relapse in chemotherapy-based myeloablative and fludarabine-based reduced-intensity regimens. Regarding total-body-irradiation–based myeloablative regimens, more intensive MTX exposure was associated with lower rates of grade II–IV acute GVHD and improved GVHD-free/relapse-free survival compared with low-dose MTX. For chemotherapy-based myeloablative and fludarabine-based reduced-intensity regimens, standard-dose MTX generally provided the most favorable balance between GVHD control and survival. These nationwide data suggest that MTX exposure should be tailored to the conditioning backbone rather than uniformly reduced, and provide pragmatic, regimen-specific benchmarks to individualize GVHD prophylaxis and guide future prospective and international comparative studies of CBT for high-risk acute myeloid leukemia.
SN  - 2045-2322
ER  -