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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Satoshi Yamasaki,
  • Masamitsu Yanada,
  • Tomomi Toubai,
  • Kaito Harada,
  • Masatsugu Tanaka,
  • Makoto Onizuka,
  • Tetsuya Nishida,
  • Norimichi Hattori,
  • Toru Izumi,
  • Satoshi Takahashi,
  • Masashi Sawa,
  • Yuta Katayama,
  • Toshiro Kawakita,
  • Jun Ishikawa,
  • Masahito Tokunaga,
  • Koichi Onodera,
  • Koji Nagafuji,
  • Hideki Nakasone,
  • Fumihiko Ishimaru,
  • Junya Kanda,
  • Yoshiko Atsuta,
  • Takaaki Konuma

摘要

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.