Improved survival after single-unit cord blood transplantation using fludarabine and melphalan-based reduced-intensity conditioning for malignant lymphoma: impact of melphalan dose and graft-versus-host disease prophylaxis with mycophenolate mofetil

Kazuki Sakatoku, Sung Won Kim, Hiroshi Okamura, Minoru Kanaya, Koji Kato, Satoshi Yamasaki, Naoyuki Uchida, Hikaru Kobayashi, Takahiro Fukuda, Nobuyuki Takayama, Jun Ishikawa, Hideyuki Nakazawa, Masatoshi Sakurai, Takashi Ikeda, Tadakazu Kondo, Satoshi Yoshioka, Toshihiro Miyamoto, Takafumi Kimura, Tatsuo Ichinohe, Yoshiko AtsutaEisei Kondo

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Abstract

We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma.

Original languageEnglish
Pages (from-to)2743-2757
Number of pages15
JournalAnnals of Hematology
Volume101
Issue number12
DOIs
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Hematology

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