TY - JOUR
T1 - Improved survival after single-unit cord blood transplantation using fludarabine and melphalan-based reduced-intensity conditioning for malignant lymphoma
T2 - impact of melphalan dose and graft-versus-host disease prophylaxis with mycophenolate mofetil
AU - Sakatoku, Kazuki
AU - Kim, Sung Won
AU - Okamura, Hiroshi
AU - Kanaya, Minoru
AU - Kato, Koji
AU - Yamasaki, Satoshi
AU - Uchida, Naoyuki
AU - Kobayashi, Hikaru
AU - Fukuda, Takahiro
AU - Takayama, Nobuyuki
AU - Ishikawa, Jun
AU - Nakazawa, Hideyuki
AU - Sakurai, Masatoshi
AU - Ikeda, Takashi
AU - Kondo, Tadakazu
AU - Yoshioka, Satoshi
AU - Miyamoto, Toshihiro
AU - Kimura, Takafumi
AU - Ichinohe, Tatsuo
AU - Atsuta, Yoshiko
AU - Kondo, Eisei
N1 - Funding Information:
This work was supported by a grant from the National Cancer Research and Development Fund (2020-A-15).
Funding Information:
K.K. received honoraria from MSD K.K., Chugai Pharmaceutical Co., Ltd. N.T. received honoraria from Chugai Pharmaceutical Co., Ltd. and Pfizer Inc., Sanofi S.A., and research funding from Chugai Pharmaceutical Co., Ltd. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1007/s00277-022-04990-w
DO - 10.1007/s00277-022-04990-w
M3 - Article
C2 - 36195679
AN - SCOPUS:85139701505
SN - 0939-5555
VL - 101
SP - 2743
EP - 2757
JO - Annals of Hematology
JF - Annals of Hematology
IS - 12
ER -