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

Ann Hematol. 2022 Dec;101(12):2743-2757. doi: 10.1007/s00277-022-04990-w. Epub 2022 Oct 5.


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.

Keywords: Cord blood transplantation; Graft-versus-host disease prophylaxis; Lymphoma; Melphalan dose; Reduced-intensity conditioning.

MeSH terms

  • Adult
  • Calcineurin Inhibitors / therapeutic use
  • Cord Blood Stem Cell Transplantation* / methods
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphoma* / drug therapy
  • Melphalan / therapeutic use
  • Methotrexate
  • Mycophenolic Acid / therapeutic use
  • Neoplasm Recurrence, Local / drug therapy
  • Transplantation Conditioning / methods


  • Mycophenolic Acid
  • Melphalan
  • fludarabine
  • Calcineurin Inhibitors
  • Methotrexate